Author: "PELLERI, MC" - Searchworks@Jio Institute Digital Library Search Results

54 results on '"PELLERI, MC"'

1. Biologia e genetica. Con e-book. Con software di simulazione

Author: De Leo, G, Fasano, S, Ginelli, E, Alessandro, R, Antognelli, C, Barisani, D, Brancolini, C, Di Bella MA, Fontana, S, Meneveri, R, Mezzasoma, L, Minucci, S, Modesti, A, Olivieri, A, Pelleri, Mc, Pierantoni, R, Purrello, M, Robledo, R, Sidoti, A, Talesa, Vn, and Tognon, M
Published: 2020

2. Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Author: Brown, P, Tan, A-C, El-Esawi, MA, Liehr, T, Blanck, O, Gladue, DP, Almeida, GMF, Cernava, T, Sorzano, CO, Yeung, AWK, Engel, MS, Chandrasekaran, AR, Muth, T, Staege, MS, Daulatabad, SV, Widera, D, Zhang, J, Meule, A, Honjo, K, Pourret, O, Yin, C-C, Zhang, Z, Cascella, M, Flegel, WA, Goodyear, CS, van Raaij, MJ, Bukowy-Bieryllo, Z, Campana, LG, Kurniawan, NA, Lalaouna, D, Huttner, FJ, Ammerman, BA, Ehret, F, Cobine, PA, Tan, E-C, Han, H, Xia, W, McCrum, C, Dings, RPM, Marinello, F, Nilsson, H, Nixon, B, Voskarides, K, Yang, L, Costa, VD, Bengtsson-Palme, J, Bradshaw, W, Grimm, DG, Kumar, N, Martis, E, Prieto, D, Sabnis, SC, Amer, SEDR, Liew, AWC, Perco, P, Rahimi, F, Riva, G, Zhang, C, Devkota, HP, Ogami, K, Basharat, Z, Fierz, W, Siebers, R, Tan, K-H, Boehme, KA, Brenneisen, P, Brown, JAL, Dalrymple, BP, Harvey, DJ, Ng, G, Werten, S, Bleackley, M, Dai, Z, Dhariwal, R, Gelfer, Y, Hartmann, MD, Miotla, P, Tamaian, R, Govender, P, Gurney-Champion, OJ, Kauppila, JH, Zhang, X, Echeverria, N, Subhash, S, Sallmon, H, Tofani, M, Bae, T, Bosch, O, Cuiv, PO, Danchin, A, Diouf, B, Eerola, T, Evangelou, E, Filipp, FV, Klump, H, Kurgan, L, Smith, SS, Terrier, O, Tuttle, N, Ascher, DB, Janga, SC, Schulte, LN, Becker, D, Browngardt, C, Bush, SJ, Gaullier, G, Ide, K, Meseko, C, Werner, GDA, Zaucha, J, Al-Farha, AA, Greenwald, NF, Popoola, SI, Rahman, MS, Xu, J, Yang, SY, Hiroi, N, Alper, OM, Baker, CI, Bitzer, M, Chacko, G, Debrabant, B, Dixon, R, Forano, E, Gilliham, M, Kelly, S, Klempnauer, K-H, Lidbury, BA, Lin, MZ, Lynch, I, Ma, W, Maibach, EW, Mather, DE, Nandakumar, KS, Ohgami, RS, Parchi, P, Tressoldi, P, Xue, Y, Armitage, C, Barraud, P, Chatzitheochari, S, Coelho, LP, Diao, J, Doxey, AC, Gobet, A, Hu, P, Kaiser, S, Mitchell, KM, Salama, MF, Shabalin, IG, Song, H, Stevanovic, D, Yadollahpour, A, Zeng, E, Zinke, K, Alimba, CG, Beyene, TJ, Cao, Z, Chan, SS, Gatchell, M, Kleppe, A, Piotrowski, M, Torga, G, Woldesemayat, AA, Cosacak, MI, Haston, S, Ross, SA, Williams, R, Wong, A, Abramowitz, MK, Effiong, A, Lee, S, Abid, MB, Agarabi, C, Alaux, C, Albrecht, DR, Atkins, GJ, Beck, CR, Bonvin, AMJJ, Bourke, E, Brand, T, Braun, RJ, Bull, JA, Cardoso, P, Carter, D, Delahay, RM, Ducommun, B, Duijf, PHG, Epp, T, Eskelinen, E-L, Fallah, M, Farber, DB, Fernandez-Triana, J, Feyerabend, F, Florio, T, Friebe, M, Furuta, S, Gabrielsen, M, Gruber, J, Grybos, M, Han, Q, Heinrich, M, Helantera, H, Huber, M, Jeltsch, A, Jiang, F, Josse, C, Jurman, G, Kamiya, H, de Keersmaecker, K, Kristiansson, E, de Leeuw, F-E, Li, J, Liang, S, Lopez-Escamez, JA, Lopez-Ruiz, FJ, Marchbank, KJ, Marschalek, R, Martin, CS, Miele, AE, Montagutelli, X, Morcillo, E, Nicoletti, R, Niehof, M, O'Toole, R, Ohtomo, T, Oster, H, Palma, J-A, Paterson, R, Peifer, M, Portilla, M, Portillo, MC, Pritchard, AL, Pusch, S, Raghava, GPS, Roberts, NJ, Ross, K, Schuele, B, Sergeant, K, Shen, J, Stella, A, Sukocheva, O, Uversky, VN, Vanneste, S, Villet, MH, Viveiros, M, Vorholt, JA, Weinstock, C, Yamato, M, Zabetakis, I, Zhao, X, Ziegler, A, Aizat, WM, Atlas, L, Bridges, KM, Chakraborty, S, Deschodt, M, Domingues, HS, Esfahlani, SS, Falk, S, Guisado, JL, Kane, NC, Kueberuwa, G, Lau, CL, Liang, D, Liu, E, Luu, AM, Ma, C, Ma, L, Moyer, R, Norris, AD, Panthee, S, Parsons, JR, Peng, Y, Pinto, IM, Reschke, CR, Sillanpaa, E, Stewart, CJ, Uhle, F, Yang, H, Zhou, K, Zhu, S, Ashry, M, Bergsland, N, Berthold, M, Chen, C-E, Colella, V, Cuypers, M, Eskew, EA, Fan, X, Gajda, M, Gonzalezlez-Prendes, R, Goodin, A, Graham, EB, Groen, EJN, Gutierrez-Sacristan, A, Habes, M, Heffler, E, Higginbottom, DB, Janzen, T, Jayaraman, J, Jibb, LA, Jongen, S, Kinyanjui, T, Koleva-Kolarova, RG, Li, Z, Liu, Y-P, Lund, BA, Lussier, AA, Mier, P, Moore, MD, Nagler, K, Orme, MW, Pearson, JA, Prajapati, AS, Saito, Y, Troder, SE, Uchendu, F, Verloh, N, Voutchkova, DD, Abu-Zaid, A, Bakkach, J, Baumert, P, Dono, M, Hanson, J, Herbelet, S, Hobbs, E, Kulkarni, A, Liu, S, Loft, ND, Reddan, T, Senghore, T, Vindin, H, Xu, H, Bannon, R, Chen, B, Cheung, JTK, Cooper, J, Esnakul, AK, Feghali, KA, Ghelardi, E, Gnasso, A, Horbar, J, Lai, HM, Ma, R, Pan, Z, Peres, MA, Pranata, R, Seow, E, Sydes, M, Testoni, I, Westermair, AL, Yang, Y, Afnan, M, Albiol, J, Albuquerque, LG, Amiya, E, Amorim, RM, An, Q, Andersen, SU, Aplin, JD, Argyropoulos, C, Asmann, YW, Assaeed, AM, Atanasov, AG, Atchison, DA, Avery, SV, Avillach, P, Baade, PD, Backman, L, Badie, C, Baldi, A, Ball, E, Bardot, O, Barnett, AG, Basner, M, Batra, J, Bazanova, OM, Beale, A, Beddoe, T, Bell, ML, Berezikov, E, Berners-Price, S, Bernhardt, P, Berry, E, Bessa, TB, Billington, C, Birch, J, Blakely, RD, Blaskovich, MAT, Blum, R, Boelaert, M, Bogdanos, D, Bosch, C, Bourgoin, T, Bouvard, D, Boykin, LM, Bradley, G, Braun, D, Brownlie, J, Bruhl, A, Burt, A, Butler, LM, Byrareddy, SN, Byrne, HJ, Cabantous, S, Calatayud, S, Candal, E, Carlson, K, Casillas, S, Castelvetro, V, Caswell, PT, Cavalli, G, Cerovsky, V, Chagoyen, M, Chen, C-S, Chen, DF, Chen, H, Chen, J-T, Chen, Y, Cheng, C, Cheng, J, Chinapaw, M, Chinopoulos, C, Cho, WCS, Chong, L, Chowdhury, D, Chwalibog, A, Ciresi, A, Cockcroft, S, Conesa, A, Cook, PA, Cooper, DN, Coqueret, O, Corea, EM, Costa, E, Coupland, C, Crawford, SY, Cruz, AD, Cui, H, Cui, Q, Culver, DC, D'Angiulli, A, Dahms, TES, Daigle, F, Dalgleish, R, Danielsen, HE, Darras, S, Davidson, SM, Day, DA, Degirmenci, V, Demaison, L, Devriendt, K, Ding, J, Dogan, Y, Dong, XC, Donner, CF, Dressick, W, Drevon, CA, Duan, H, Ducho, C, Dumaz, N, Dwarakanath, BS, Ebell, MH, Eisenhardt, S, Elkum, N, Engel, N, Erickson, TB, Fairhead, M, Faville, MJ, Fejzo, MS, Festa, F, Feteira, A, Flood-Page, P, Forsayeth, J, Fox, SA, Franks, SJ, Frentiu, FD, Frilander, MJ, Fu, X, Fujita, S, Galea, I, Galluzzi, L, Gani, F, Ganpule, AP, Garcia-Alix, A, Gedye, K, Giordano, M, Giunta, C, Gleeson, PA, Goarant, C, Gong, H, Gora, D, Gough, MJ, Goyal, R, Graham, KE, Grande-Perez, A, Graves, PM, Greidanus, H, Grice, D, Grunau, C, Gumulya, Y, Guo, Y, Gurevich, VV, Gusev, O, Hacker, E, Hage, SR, Hagen, G, Hahn, S, Haller, DM, Hammerschmidt, S, Han, J, Han, R, Handfield, M, Hapuarachchi, HC, Harder, T, Hardingham, JE, Heck, M, Heers, M, Hew, KF, Higuchi, Y, St Hilaire, C, Hilton, R, Hodzic, E, Hone, A, Hongoh, Y, Hu, G, Huber, HP, Hueso, LE, Huirne, J, Hurt, L, Idborg, H, Ikeo, K, Ingley, E, Jakeman, PM, Jensen, A, Jia, H, Jia, S, Jiang, J, Jiang, X, Jin, Y, Jo, D, Johnson, AM, Johnston, M, Jonscher, KR, Jorens, PG, Jorgensen, JOL, Joubert, JW, Jung, S-H, Junior, AM, Kahan, T, Kamboj, SK, Kang, Y-K, Karamanos, Y, Karp, NA, Kelly, R, Kenna, R, Kennedy, J, Kersten, B, Khalaf, RA, Khalid, JM, Khatlani, T, Khider, T, Kijanka, GS, King, SRB, Kluz, T, Knox, P, Kobayashi, T, Koch, K-W, Kohonen-Corish, MRJ, Kong, X, Konkle-Parker, D, Korpela, KM, Kostrikis, LG, Kraiczy, P, Kratz, H, Krause, G, Krebsbach, PH, Kristensen, SR, Kumari, P, Kunimatsu, A, Kurdak, H, Kwon, YD, Lachat, C, Lagisz, M, Laky, B, Lammerding, J, Lange, M, Larrosa, M, Laslett, AL, LeClair, EE, Lee, K-W, Lee, M-Y, Lee, M-S, Li, G, Lieb, K, Lim, YY, Lindsey, ML, Line, P-D, Liu, D, Liu, F, Liu, H, Lloyd, VK, Lo, T-W, Locci, E, Loidl, J, Lorenzen, J, Lorkowski, S, Lovell, NH, Lu, H, Lu, W, Lu, Z, Luengo, GS, Lundh, L-G, Lysy, PA, Mabb, A, Mack, HG, Mackey, DA, Mahdavi, SR, Maher, P, Maher, T, Maity, SN, Malgrange, B, Mamoulakis, C, Mangoni, AA, Manke, T, Manstead, ASR, Mantalaris, A, Marsal, J, Marschall, H-U, Martin, FL, Martinez-Raga, J, Martinez-Salas, E, Mathieu, D, Matsui, Y, Maza, E, McCutcheon, JE, Mckay, GJ, McMillan, B, McMillan, N, Meads, C, Medina, L, Merrick, BA, Metzger, DW, Meunier, FA, Michaelis, M, Micheau, O, Mihara, H, Mintz, EM, Mizukami, T, Moalic, Y, Mohapatra, DP, Monteiro, A, Montes, M, Moran, JV, Morozov, SY, Mort, M, Murai, N, Murphy, DJ, Murphy, SK, Murray, SA, Naganawa, S, Nammi, S, Nasios, G, Natoli, RM, Nguyen, F, Nicol, C, van Nieuwerburgh, F, Nilsen, EB, Nobile, CJ, O'Mahony, M, Ohlsson, S, Olatunbosun, O, Olofsson, P, Ortiz, A, Ostrikov, K, Otto, S, Outeiro, TF, Ouyang, S, Paganoni, S, Page, A, Palm, C, Paradies, Y, Parsons, MH, Parsons, N, Pascal, P, Paul, E, Peckham, M, Pedemonte, N, Pellizzon, MA, Petrelli, M, Pichugin, A, Pinto, CJC, Plevris, JN, Pollesello, P, Polz, M, Ponti, G, Porcelli, P, Prince, M, Quinn, GP, Quinn, TJ, Ramula, S, Rappsilber, J, Rehfeldt, F, Reiling, JH, Remacle, C, Rezaei, M, Riddick, EW, Ritter, U, Roach, NW, Roberts, DD, Robles, G, Rodrigues, T, Rodriguez, C, Roislien, J, Roobol, MJ, Rowe, JA, Ruepp, A, van Ruitenbeek, J, Rust, P, Saad, S, Sack, GH, Santos, M, Saudemont, A, Sava, G, Schrading, S, Schramm, A, Schreiber, M, Schuler, S, Schymkowitz, J, Sczyrba, A, Seib, KL, Shi, H-P, Shimada, T, Shin, J-S, Shortt, C, Silveyra, P, Skinner, D, Small, I, Smeets, PAM, So, P-W, Solano, F, Sonenshine, DE, Song, J, Southall, T, Speakman, JR, Srinivasan, MV, Stabile, LP, Stasiak, A, Steadman, KJ, Stein, N, Stephens, AW, Stewart, DI, Stine, K, Storlazzi, C, Stoynova, NV, Strzalka, W, Suarez, OM, Sultana, T, Sumant, AV, Summers, MJ, Sun, G, Tacon, P, Tanaka, K, Tang, H, Tanino, Y, Targett-Adams, P, Tayebi, M, Tayyem, R, Tebbe, CC, Telfer, EE, Tempel, W, Teodorczyk-Injeyan, JA, Thijs, G, Thorne, S, Thrift, AG, Tiffon, C, Tinnefeld, P, Tjahjono, DH, Tolle, F, Toth, E, del Tredici, AL, Tsapas, A, Tsirigotis, K, Turak, A, Tzotzos, G, Udo, EE, Utsumi, T, Vaidyanathan, S, Vaillant, M, Valsesia, A, Vandenbroucke, RE, Veiga, FH, Vendrell, M, Vesk, PA, Vickers, P, Victor, VM, Villemur, R, Vohl, M-C, Voolstra, CR, Vuillemin, A, Wakelin, S, Waldron, L, Walsh, LJ, Wang, AY, Wang, F, Wang, Y, Watanabe, Y, Weigert, A, Wen, J-C, Wham, C, White, EP, Wiener, J, Wilharm, G, Wilkinson, S, Willmann, R, Wilson, C, Wirth, B, Wojan, TR, Wolff, M, Wong, BM, Wu, T-W, Wuerbel, H, Xiao, X, Xu, D, Xu, JW, Xue, B, Yalcin, S, Yan, H, Yang, E-C, Yang, S, Yang, W, Ye, Y, Ye, Z-Q, Yli-Kauhaluoma, J, Yoneyama, H, Yu, Y, Yuan, G-C, Yuh, C-H, Zaccolo, M, Zeng, C, Zevnik, B, Zhang, L, Zhang, Y, Zhang, Z-Y, Zhao, Y, Zhou, M, Zuberbier, T, Aanei, CM, Ahmad, R, Al-Lawama, M, Alanio, A, Allardyce, J, Alonso-Caneiro, D, Atack, JM, Baier, D, Bansal, A, Benezeth, Y, Berbesque, C, Berrevoet, F, Biedermann, PHW, Bijleveld, E, Bittner, F, Blombach, F, Van den Bos, W, Boudreau, SA, Bramoweth, AD, Braubach, O, Cai, Y, Campbell, M, Catry, T, Chen, X, Cheng, S, Chung, H-J, Chavez-Fumagalli, MA, Conway, A, Costa, BM, Cyr, N, Dean, LT, Denzel, MS, Dlamini, SV, Dudley, KJ, Dufies, M, Ecke, T, Eckweiler, D, Eixarch, E, El-Adawy, H, Emmrich, JV, Eustace, AJ, Falter-Wagner, CM, Fuss, J, Gao, J, Gill, MR, Gloyn, L, Goggs, R, Govinden, U, Greene, G, Greiff, V, Grundle, DS, Gruneberg, P, Gumede, N, Haore, G, Harrison, P, Hoenner, X, Hojsgaard, D, Hori, H, Ikonomopoulou, MP, Jeurissen, P, Johnson, DM, Kabra, D, Kamagata, K, Karmakar, C, Kasian, O, Kaye, LK, Khan, MM, Kim, Y-M, Kish, JK, Kobold, S, Kohanbash, G, Kohls, G, Kugler, J-M, Kumar, G, Lacy-Colson, J, Latif, A, Lauschke, VM, Li, B, Lim, CJ, Liu, X, Lu, J-J, Lu, Q, Mahavadi, P, Marzocchi, U, McGarrigle, CA, van Meerten, T, Min, R, Moal, I, Molari, M, Molleman, L, Mondal, SR, Van de Mortel, T, Moss, WN, Moultos, OA, Mukherjee, M, Nakayama, K, Narayan, E, Navaratnarajah, Neumann, P-A, Nie, J, Nie, Y, Niemeyer, F, Fiona, Nwaiwu, O, Oldenmenger, WH, Olumayede, E, Ou, J, Pallebage-Gamarallage, M, Pearce, SP, Pelkonen, T, Pelleri, MC, Pereira, JL, Pheko, M, Pinto, KA, Piovesan, A, Pluess, M, Podolsky, IM, Prescott, J, Qi, D, Qi, X, Raikou, VD, Ranft, A, Rhodes, J, Rotge, J-Y, Rowe, AD, Saggar, M, Schuon, RA, Shahid, S, Shalchyan, V, Shirvalkar, P, Shiryayev, O, Singh, J, Smout, MJ, Soares, A, Song, C, Srivastava, K, Srivastava, RK, Sun, J, Szabo, A, Szymanski, W, Tai, CNP, Takeuchi, H, Tanadini-Lang, S, Tang, F, Tao, W, Theron, G, Tian, CF, Tian, Y-S, Tuttle, LM, Valenti, A, Verlot, P, Walker, M, Wang, J, Welter, D, Winslade, M, Wu, D, Wu, Y-R, Xiao, H, Xu, B, Xu, Z, Yang, D, Yang, M, Yankilevich, P, You, Y, Yu, C, Zhan, J, Zhang, G, Zhang, K, Zhang, T, Zhao, G, Zhao, J, Zhou, X, Zhu, Z, Ajani, PA, Anazodo, UC, Bagloee, SA, Bail, K, Bar, I, Bathelt, J, Benkeser, D, Bernier, ML, Blanchard, AM, Boakye, DW, Bonatsos, V, Boon, MH, Bouboulis, G, Bromfield, E, Brown, J, Bul, KCM, Burton, KJ, Butkowski, EG, Carroll, G, Chao, F, Charrier, EE, Chen, Y-C, Chenguang, Choi, JR, Christoffersen, T, Comel, JC, Cosse, C, Cui, Y, van Dessel, P, Dhaval, Diodato, D, Duffey, M, Dutt, A, Egea, LG, El-Said, M, Faye, M, Fernandez-Fernandez, B, Foley, KG, Founou, LL, Fu, F, Gadelkareem, RA, Galimov, E, Garip, G, Gemmill, A, Gouil, Q, Grey, J, Gridneva, Z, Grothe, MJ, Grebert, T, Guerrero, F, Guignard, L, Haenssgen, MJ, Hasler, D, Holgate, JY, Huang, A, Hulse-Kemp, AM, Jean-Quartier, C, Jeon, S-M, Jia, Y, Jutzeler, C, Kalatzis, P, Karim, M, Karsay, K, Keitel, A, Kempe, A, Keown, JR, Khoo, CM, Khwaja, N, Kievit, RA, Kosanic, A, Koutoukidis, DA, Kramer, P, Kumar, D, Kirag, N, Lanza, G, Le, TD, Leem, JW, Leightley, D, Leite, A, Lercher, L, Li, Y, Lim, R, Lima, LRA, Lin, L, Ling, T, Liu, Y, Liu, Z, Lu, Y, Lum, FM, Luo, H, Machhi, J, Macleod, A, Macwan, I, Madala, HR, Madani, N, de Maio, N, Makowiecki, K, Mallinson, DJ, Margelyte, R, Maria, C, Markonis, Y, Marsili, L, Mavoa, S, McWilliams, L, Megersa, M, Mendes, CSM, Menichetti, J, Mercieca-Bebber, R, Miller, JJ, Minde, D-PM, Minges, A, Mishra, E, Mishra, VR, Moores, C, Morrice, N, Moskalensky, AE, Navarin, N, Negera, E, Nolet, P, Nordberg, A, Norden, R, Nowicki, JP, Olova, N, Olszewski, P, Onzima, R, Pan, C-L, Park, C, Park, DI, Park, S, Patil, CD, Pedro, SA, Perry, SR, Peter, J, Peterson, BM, Pezzuolo, A, Pozdnyakov, I, Qian, S, Qin, L, Rafe, A, Raote, I, Raza, A, Rebl, H, Refai, O, Regan, T, Richa, T, Richardson, MF, Robinson, KR, Rossoni, L, Rouet, R, Safaei, S, Schneeberger, PHH, Schwotzer, D, Sebastian, A, Selinski, J, Seltmann, S, Sha, F, Shalev, N, Shang, J-L, Singer, J, Singh, M, Smith, T, Solomon-Moore, E, Song, L, Soraggi, S, Stanley, R, Steckhan, N, Strobl, F, Subissi, L, Supriyanto, I, Surve, CR, Suzuki, T, Syme, C, Sorelius, K, Tang, Y, Tantawy, M, Tennakoon, S, Teseo, S, Toelzer, C, Tomov, N, Tovar, M, Tran, L, Tripathi, S, Tuladhar, AM, Ukubuiwe, AC, Ung, COL, Valgepea, K, Vatanparast, H, Vidal, A, Wang, Q, Watari, R, Webster, R, Wei, J, Wibowo, D, Wingenbach, TSH, Xavier, RM, Xiao, S, Xiong, P, Xu, S, Yao, R, Yao, W, Yin, Q, Zaitsu, M, Zeineb, Z, Zhan, X-Y, Zhang, R, Zhang, W, Zheng, S, Zhou, B, Ahmad, H, Akinwumi, SA, Albery, GF, Alhowimel, A, Ali, J, Alshehri, M, Alsuhaibani, M, Anikin, A, Azubuike, SO, Bach-Mortensen, A, Baltiansky, L, Bartas, M, Belachew, KY, Bhardwaj, V, Binder, K, Bland, NS, Boah, M, Bullen, B, Calabro, GE, Callahan, TJ, Cao, B, Chalmers, K, Chang, W, Che, Z, Chen, ATY, Chen, Z, Choi, Y, Chowdhury, MAK, Christensen, MR, Cooke, RSC, Cottini, M, Covington, NV, Cunningham, C, Delarocque, J, Devos, L, Dhar, AR, Ding, K-F, Dong, K, Dong, Z, Dreyer, N, Ekstrand, C, Fardet, T, Feleke, BE, Feurer, T, Freitas, 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Strobl, F, Subissi, L, Supriyanto, I, Surve, CR, Suzuki, T, Syme, C, Sorelius, K, Tang, Y, Tantawy, M, Tennakoon, S, Teseo, S, Toelzer, C, Tomov, N, Tovar, M, Tran, L, Tripathi, S, Tuladhar, AM, Ukubuiwe, AC, Ung, COL, Valgepea, K, Vatanparast, H, Vidal, A, Wang, Q, Watari, R, Webster, R, Wei, J, Wibowo, D, Wingenbach, TSH, Xavier, RM, Xiao, S, Xiong, P, Xu, S, Yao, R, Yao, W, Yin, Q, Zaitsu, M, Zeineb, Z, Zhan, X-Y, Zhang, R, Zhang, W, Zheng, S, Zhou, B, Ahmad, H, Akinwumi, SA, Albery, GF, Alhowimel, A, Ali, J, Alshehri, M, Alsuhaibani, M, Anikin, A, Azubuike, SO, Bach-Mortensen, A, Baltiansky, L, Bartas, M, Belachew, KY, Bhardwaj, V, Binder, K, Bland, NS, Boah, M, Bullen, B, Calabro, GE, Callahan, TJ, Cao, B, Chalmers, K, Chang, W, Che, Z, Chen, ATY, Chen, Z, Choi, Y, Chowdhury, MAK, Christensen, MR, Cooke, RSC, Cottini, M, Covington, NV, Cunningham, C, Delarocque, J, Devos, L, Dhar, AR, Ding, K-F, Dong, K, Dong, Z, Dreyer, N, Ekstrand, C, Fardet, T, Feleke, BE, Feurer, T, Freitas, A, Gao, T, Asefa, NG, Giganti, F, Grabowski, P, Guerra-Mora, JR, Guo, C, Guo, X, Gupta, H, He, S, Heijne, M, Heinemann, S, Hogrebe, A, Huang, Z, Iskander-Rizk, S, Iyer, LM, Jahan, Y, James, AS, Joel, E, Joffroy, B, Jegousse, C, Kambondo, G, Karnati, P, Kaya, C, Ke, A, Kelly, D, Kickert, R, Kidibule, PE, Kieselmann, JP, Kim, HJ, Kitazawa, T, Lamberts, A, Liang, H, Linn, SN, Litfin, T, Liusuo, W, Lygirou, V, Mahato, AK, Mai, Z-M, Major, RW, Mali, S, Mallis, P, Mao, W, Marvin-Dowle, K, Mason, LD, Merideth, B, Merino-Plaza, MJ, Merlaen, B, Messina, R, Mishra, AK, Muhammad, J, Musinguzi, C, Nanou, A, Naqash, A, Nguyen, JT, Nguyen, TTH, Ni, D, Nida, Notcovich, S, Ohst, B, Ollivier, QR, Osses, DF, Peng, X, Plantinga, A, Pulia, M, Rafiq, M, Raman, A, Raucher-Chene, D, Rawski, R, Ray, A, Razak, LA, Rudolf, K, Rusch, P, Sadoine, ML, Schmidt, A, Schurr, R, Searles, S, Sharma, S, Sheehan, B, Shi, C, Shohayeb, B, Sommerlad, A, Strehlow, J, Sun, X, Sundar, R, Taherzadeh, G, Tahir, NDM, Tang, J, Testa, J, Tian, Z, Tingting, Q, Verheijen, GP, Vickstrom, C, Wang, T, Wang, X, Wang, Z, Wei, P, Wilson, A, Wyart, Yassine, A-A, Yousefzadeh, A, Zare, A, Zeng, Z, Zhang, H, Zhou, J, Zhu, D, Adamo, V, Adeyemo, AA, Aggelidou, M, Al-Owaifeer, AM, Al-Riyami, AZ, Alzghari, SK, Andersen, V, Angus, K, Asaduzzaman, M, Asady, H, Ato, D, Bai, X, Baines, RL, Ballantyne, M, Ban, B, Beck, J, Ben-Nafa, W, Black, E, Blancher, A, Blankstein, R, Bodagh, N, Borges, PAV, Brooks, A, Brox-Ponce, J, Brunetti, A, Canham, CD, Carninci, P, Carvajal, R, Chang, SC, Chao, J, Chatterjee, P, Chhatriwalla, AK, Chikowe, I, Chuang, T-J, Collevatti, RG, Valera-Cornejo, DA, Cuenda, A, Dao, M, Dauga, D, Deng, Z, Devkota, K, Doan, LV, Elewa, YHA, Fan, D, Faruk, M, Feifei, S, Ferguson, TS, Fleres, F, Foster, EJ, Foster, CS, Furer, T, Gao, Y, Garcia-Rivera, EJ, Gazdar, A, George, RB, Ghosh, S, Gianchecchi, E, Gleason, JM, Hackshaw, A, Hall, A, Hall, R, Harper, P, Hogg, WE, Huang, G, Hunter, KE, IJzerman, AP, Jesus, C, Jian, G, Lewis, JS, Kanj, SS, Kaur, H, Kheir, F, Kichatova, VS, Kiyani, M, Klein, R, Kovesi, T, Kraschnewski, JL, Kumar, AP, Labutin, D, Lazo-Langner, A, Leclercq, G, Li, M, Li, Q, Li, T, Liao, W-T, Liao, Z-Y, Lin, J, Lizer, J, Lobreglio, G, Lowies, C, Lu, C, Majeed, H, Martin, A, Martinez-Sobrido, L, Meresh, E, Middelveen, M, Mohebbi, A, Mota, J, Mozaheb, Z, Muyaya, L, Nandhakumar, A, Ng, SHX, Obeidat, M, Oh, D-H, Owais, M, Pace-Asciak, P, Panwar, A, Patterson, C, Penagos-Tabaree, F, Pianosi, PT, Pinzi, V, Pridans, C, Psaroulaki, A, Pujala, RK, Pulido-Arjona, L, Qi, P-F, Rahman, P, Rai, NK, Rassaf, T, Refardt, J, Ricciardi, W, Riess, O, Rovas, A, Sacks, FM, Saleh, S, Sampson, C, Schmutz, A, Sepanski, R, Sharma, N, Spearman, P, Subramaniapillai, M, Swali, R, Tan, CM, Tellechea, JI, Thomas, L-M, Tong, X, Veys, R, Vitriol, V, Wang, H-D, Waugh, J, Webb, SA, Williams, BA, Workman, AD, Xiang, T, Xie, L-X, Xu, T, Yang, C, Yoon, JG, Yuan, CM, Zaritsky, A, Zhao, H, Zuckerman, H, Lyu, R, Pullan, W, and Zhou, Y
Published: 2019

3. An integrated route to identifying new pathogenesis-based therapeutic approaches for trisomy 21 (Down Syndrome) following the thought of Jérôme Lejeune

Author: Strippoli, P, Pelleri, M, Caracausi, M, Vitale, L, Piovesan, A, Locatelli, C, Mimmi, M, Berardi, A, Ricotta, D, Radeghieri, A, Barisani, D, Basik, M, Monaco, M, Ghezzo, A, Seri, M, Cocchi, G, Pelleri, MC, Caracausi,M, Mimmi,MC, Berardi, AC, Monaco, MC, Cocchi, G., BARISANI, DONATELLA, Strippoli, P, Pelleri, M, Caracausi, M, Vitale, L, Piovesan, A, Locatelli, C, Mimmi, M, Berardi, A, Ricotta, D, Radeghieri, A, Barisani, D, Basik, M, Monaco, M, Ghezzo, A, Seri, M, Cocchi, G, Pelleri, MC, Caracausi,M, Mimmi,MC, Berardi, AC, Monaco, MC, Cocchi, G., and BARISANI, DONATELLA
Abstract: Down Syndrome (DS) is the most frequent human chromosomal disorder. Main symptoms include intellectual disability (ID), cardiovascular defects and craniofacial dysmorphisms. Despite ID being measured by a test of symbolic logic skills, it is common for children with DS to arouse a climate of affective intensity greater than the norm. In 1959, Jérôme Lejeune (1926-1994) and coll. described an additional chromosome 21 (Hsa21) in children with DS (trisomy 21), giving origin to the field of medical genetics. Remarkably, the discovery of trisomy 21 had relevant social consequences for the affected children, in that their parents were no longer suspected to be alcoholics or infected with syphilis. Although it is broadly agreed that the DS phenotype originates from the altered expression of the genes located on Hsa21, its molecular pathogenesis is still unknown. To date, no therapy is recognized and recommended by guidelines as being effective in improving the cognitive abilities of persons with DS. The aim of this article is to categorize main therapeutical approaches or pathways to new approaches reported in the biomedical literature, to extract critical methodological points from the works of Lejeune and then to propose a new research project aimed to generate and integrate clinical, biochemical, genetic and bioinformatic data in order to identify novel therapeutic targets for this form of trisomy. We show here that nearly all the current lines of research were pursued, theorized or foreseen by Lejeune, and that central points of his method remain current: positive hypothesis about the existence of a solution, envision of systematic investigation of cell machinery, anchoring of clinical and biochemical finding to the chromosome physical map, and continuing clinical observation of the affected children. We therefore propose a project aimed at producing both experimentally and by meta-analysis state-of the-art maps and databases related to clinical/phenotype, cytogeneti
Published: 2013

4. BASI DELL'ORGANIZZAZIONE BIOLOGICA

Author: M. A. DI BELLA, S. FONTANA, R. ALESSANDRO, A. OLIVIERI, A. SIDOTI, G. DE LEO, DE LEO, G, FASANO, S, GINELLI, E, DE LEO,G, FASANO,S, ALESSANDRO,R, ANTOGNELLI,C, BARISANI,D, BRANCOLINI,C, DI BELLA, MA, FONTANA,S, MENEVERI,R, MEZZASOMA,L, MINUCCI,S, MODESTI,A, OLIVIERI,A, PELLERI, MC, PIERANTONI, R, PURRELLO, M, ROBLEDO, R, SIDOTI,A, TALESA,VN, TOGNON,M, M.A. DI BELLA, S. FONTANA, R. ALESSANDRO, A.OLIVIERI, A. SIDOTI, and G. DE LEO
Subjects: Settore BIO/13 - Biologia Applicata, cellula, evoluzione, biologia generale
Abstract: ) Classificazione degli organismi Albero dello vita ) Cellula "alle origini" Organismi e cellule Sviluppo dello teoria cellulare Proprietà fondamentali delle cellule ) Cellula procariotica Procorioti più antichi: Archaea Batteria ) Virus Caratteristiche generali Origine e natura ) Cellula eucariotica Membrane biologiche Nucleo Reticolo endoplasmatico Ribosomi Mitocondri Complesso del Golgi Lisosomi Perossisomi Citoscheletro
Published: 2020

5. Plasma metabolome and cognitive skills in Down syndrome

Author: Pierluigi Strippoli, Elisa Mannini, Francesca Pulina, Maria Chiara Pelleri, Allison Piovesan, Renzo Vianello, Chiara Locatelli, Silvia Lanfranchi, Francesca Antonaros, Paola Turano, Anna Martelli, Sara Onnivello, Claudio Luchinat, Lorenza Vitale, Guido Cocchi, Agnese Feliciello, Veronica Ghini, Giuseppe Ramacieri, Elena Cicchini, Maria Caracausi, and Antonaros F, Ghini V, Pulina F, Ramacieri G, Cicchini E, Mannini E, Martelli A, Feliciello A, Lanfranchi S, Onnivello S, Vianello R, Locatelli C, Cocchi G, Pelleri MC, Vitale L, Strippoli P, Luchinat C, Turano P, Piovesan A, Caracausi M
Subjects: Adult, Male, Metabolism, cognitive skills, Down syndrome, Down syndrome, medicine.medical_specialty, Magnetic Resonance Spectroscopy, Adolescent, Metabolite, lcsh:Medicine, Trisomy, Biochemistry, Article, chemistry.chemical_compound, Plasma, Young Adult, cognitive skills, Metabolomics, Cognition, Internal medicine, Intellectual Disability, medicine, Metabolome, Humans, Child, lcsh:Science, Univariate analysis, Multidisciplinary, Intelligence quotient, Medical genetics, Neurodevelopmental disorders, lcsh:R, Case-control study, Genomics, medicine.disease, Mitochondria, Chemistry, Metabolism, Endocrinology, chemistry, Case-Control Studies, Child, Preschool, Multivariate Analysis, Female, lcsh:Q, Down Syndrome, Metabolomics, Genomics, Medical genetics, Neurodevelopmental disorders, Biochemistry, Chemistry
Abstract: Trisomy 21 (Down syndrome, DS) is the main human genetic cause of intellectual disability (ID). Lejeune hypothesized that DS could be considered a metabolic disease, and we found that subjects with DS have a specific plasma and urinary metabolomic profile. In this work we confirmed the alteration of mitochondrial metabolism in DS and also investigated if metabolite levels are related to cognitive aspects of DS. We analyzed the metabolomic profiles of plasma samples from 129 subjects with DS and 46 healthy control (CTRL) subjects by 1H Nuclear Magnetic Resonance (NMR). Multivariate analysis of the NMR metabolomic profiles showed a clear discrimination (up to 94% accuracy) between the two groups. The univariate analysis revealed a significant alteration in 7 metabolites out of 28 assigned unambiguously. Correlations among the metabolite levels in DS and CTRL groups were separately investigated and statistically significant relationships appeared. On the contrary, statistically significant correlations among the NMR-detectable part of DS plasma metabolome and the different intelligence quotient ranges obtained by Griffiths-III or WPPSI-III tests were not found. Even if metabolic imbalance provides a clear discrimination between DS and CTRL groups, it appears that the investigated metabolomic profiles cannot be associated with the degree of ID.
Published: 2020

6. MUTAZIONI: TIPI, ORIGINI,CONSEGUENZE

Author: DI BELLA MARIA ANTONIETTA, DE LEO GIACOMO, BARISANI DONATELLA, FASANO SILVIA, MENEVERI RAFFAELLA, TOGNON MAURO, DE LEO, G, FASANO, S, GINELLI, E, DE LEO,G, FASANO,S, ALESSANDRO,R, ANTOGNELLI,C, BARISANI,D, BRANCOLINI,C, DI BELLA, MA, FONTANA,S, MENEVERI,R, MEZZASOMA,L, MINUCCI,S, MODESTI,A, OLIVIERI,A, PELLERI, MC, PIERANTONI, R, PURRELLO, M, ROBLEDO, R, SIDOTI,A, TALESA,VN, TOGNON,M, DI BELLA MARIA ANTONIETTA, DE LEO GIACOMO, BARISANI DONATELLA, FASANO SILVIA, MENEVERI RAFFAELLA, and TOGNON MAURO
Subjects: variabilità genetica, mutazioni
Abstract: Materiaie genetico, alleli, mutazione e variabilità Mutazione; tipi e classificazione Mutazioni spontanee, mutazioni indotte e agenti mutageni Ripazione del DNA meccanismi di riparo del DNA Conseguenze delle mutazioni mutaz/on/ puntiformi nelle regioni codificanti mutaz/oni nelle regioni non codificanti del gene Ricombinazione e trasposizione come eventi mutazionali crossing over ineguale,elementi mobil, espansione delle ripetizioni di tnnudeotidi Mutazioni cromosomiche (variazioni della struttura dei cromosomi) Tecniche per l'identificazione di mutazioni cromosomiche Mutazioni genomiche (variazioni del numero dei cromosomi) Variazioni del numero dei cromosomi nella specie umana Disomia uniparentale Mutazioni ed ingegneria genetica
Published: 2020

7. GENETICA GENERALE

Author: DE LEO,G, DI BELLA,MA, FASANO,S, BARISANI,D, MENEVERI,R, TOGNON,M, DE LEO, G, FASANO, S, GINELLI, E, DE LEO,G, FASANO,S, ALESSANDRO,R, ANTOGNELLI,C, BARISANI,D, BRANCOLINI,C, DI BELLA, MA, FONTANA,S, MENEVERI,R, MEZZASOMA,L, MINUCCI,S, MODESTI,A, OLIVIERI,A, PELLERI, MC, PIERANTONI, R, PURRELLO, M, ROBLEDO, R, SIDOTI,A, TALESA,VN, TOGNON,M, and DI BELLA,MA
Subjects: Genetica
Abstract: Genetica formale Metodo e prove sperimentali di Mendel Caratteri singoli e segregazione, Caratteri e assortimento indipendente, Esperienze mendeliane "ieri ed oggi", I Leggi di Mendel, I Caratteri mendeliani e reincrocio IGenetica "oltre" Mendel Dominanza incompleta Codominanza Significato e valore della dominanza e della recessività Alleila multipla Pleiotropia Interazione tra geni Alleli letali Linkage: esperienze di Morgan e associazione genica Associazione completa e associazione incompleta Basi biologiche della ricombinazione Complesso sinaptonemale, rotture a doppio filamento e crossing over Mappe fisiche e mappe genetiche Ambiente e geni L'ambiente e l'espressione dei geni: penetranza ed espressività Poligenia ed ereditarietà quantitativa Sesso e geni Determinazione del sesso nelle specie animali Cromosomi sessuali, X e Y
Published: 2020

8. Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Author: Zeineb, Zian, Brown, Peter, Tan, Aik-Choon, El-Esawi, Mohamed A., Liehr, Thomas, Blanck, Oliver, Gladue, Douglas P., Almeida, Gabriel M. F., Cernava, Tomislav, Sorzano, Carlos O., Yeung, Andy W. K., Engel, Michael S., Chandrasekaran, Arun Richard, Muth, Thilo, Staege, Martin S., Daulatabad, Swapna V., Widera, Darius, Zhang, Junpeng, Meule, Adrian, Honjo, Ken, Pourret, Olivier, Yin, Cong-Cong, Zhang, Zhongheng, Cascella, Marco, Flegel, Willy A., Goodyear, Carl S., Raaij, Mark J. van, Bukowy-Bieryllo, Zuzanna, Campana, Luca G., Kurniawan, Nicholas A., Lalaouna, David, Hüttner, Felix J., Ammerman, Brooke A., Ehret, Felix, Cobine, Paul A., Tan, Ene-Choo, Han, Hyemin, Xia, Wenfeng, McCrum, Christopher, Dings, Ruud P. M., Marinello, Francesco, Nilsson, Henrik, Nixon, Brett, Voskarides, Konstantinos, Yang, Long, Costa, Vincent D., Bengtsson-Palme, Johan, Bradshaw, William, Grimm, Dominik G., Kumar, Nitin, Martis, Elvis, Prieto, Daniel, Sabnis, Sandeep C., Amer, Said E. D. R., Liew, Alan W. C., Perco, Paul, Rahimi, Farid, Riva, Giuseppe, Zhang, Chongxing, Devkota, Hari P., Ogami, Koichi, Basharat, Zarrin, Fierz, Walter, Siebers, Robert, Tan, Kok-Hian, Boehme, Karen A., Brenneisen, Peter, Brown, James A. L., Dalrymple, Brian P., Harvey, David J., Ng, Grace, Werten, Sebastiaan, Bleackley, Mark, Dai, Zhanwu, Dhariwal, Raman, Gelfer, Yael, Hartmann, Marcus D., Miotla, Pawel, Tamaian, Radu, Govender, Pragashnie, Gurney-Champion, Oliver J., Kauppila, Joonas H., Zhang, Xiaolei, Echeverría, Natalia, Subhash, Santhilal, Sallmon, Hannes, Tofani, Marco, Bae, Taeok, Bosch, Oliver, Cuív, Páraic O., Danchin, Antoine, Diouf, Barthelemy, Eerola, Tuomas, Evangelou, Evangelos, Filipp, Fabian V., Klump, Hannes, Kurgan, Lukasz, Smith, Simon S., Terrier, Olivier, Tuttle, Neil, Ascher, David B., Janga, Sarath C., Schulte, Leon N., Becker, Daniel, Browngardt, Christopher, Bush, Stephen J., Gaullier, Guillaume, Ide, Kazuki, Meseko, Clement, Werner, Gijsbert D. A., Zaucha, Jan, Al-Farha, Abd A., Greenwald, Noah F., Popoola, Segun I., Rahman, Md Shaifur, Xu, Jialin, Yang, Sunny Y., Hiroi, Noboru, Alper, Ozgul M., Baker, Chris I., Bitzer, Michael, Chacko, George, Debrabant, Birgit, Dixon, Ray, Forano, Evelyne, Gilliham, Matthew, Kelly, Sarah, Klempnauer, Karl-Heinz, Lidbury, Brett A., Lin, Michael Z., Lynch, Iseult, Ma, Wujun, Maibach, Edward W., Mather, Diane E., Nandakumar, Kutty S., Ohgami, Robert S., Parchi, Piero, Tressoldi, Patrizio, Xue, Yu, Armitage, Charles, Barraud, Pierre, Chatzitheochari, Stella, Coelho, Luis P., Diao, Jiajie, Doxey, Andrew C., Hu, Pingzhao, Kaiser, Stefan, Mitchell, Kate M., Salama, Mohamed F., Shabalin, Ivan G., Song, Haijun, Stevanovic, Dejan, Yadollahpour, Ali, Zeng, Erliang, Zinke, Katharina, Alimba, C. G., Beyene, Tariku J., Cao, Zehong, Chan, Sherwin S., Gatchell, Michael, Kleppe, Andreas, Piotrowski, Marcin, Torga, Gonzalo, Woldesemayat, Adugna A., Cosacak, Mehmet I., Haston, Scott, Ross, Stephanie A., Williams, Richard, Wong, Alvin, Abramowitz, Matthew K., Effiong, Andem, Lee, Senhong, Abid, Muhammad Bilal, Agarabi, Cyrus, Alaux, Cedric, Albrecht, Dirk R., Atkins, Gerald J., Beck, Charles R., Bonvin, A. M. J. J., Bourke, Emer, Brand, Thomas, Braun, Ralf J., Bull, James A., Cardoso, Pedro, Carter, Dee, Delahay, Robin M., Ducommun, Bernard, Duijf, Pascal H. G., Epp, Trevor, Eskelinen, Eeva-Liisa, Fallah, Mazyar, Farber, Debora B., Fernandez-Triana, Jose, Feyerabend, Frank, Florio, Tullio, Friebe, Michael, Furuta, Saori, Gabrielsen, Mads, Gruber, Jens, Grybos, Malgorzata, Han, Qian, Heinrich, Michael, Helanterä, Heikki, Huber, Michael, Jeltsch, Albert, Jiang, Fan, Josse, Claire, Jurman, Giuseppe, Kamiya, Haruyuki, Keersmaecker, Kim de, Kristiansson, Erik, Leeuw, Frank-Erik de, Li, Jiuyong, Liang, Shide, Lopez-Escamez, Jose A., Lopez-Ruiz, Francisco J., Marchbank, Kevin J., Marschalek, Rolf, Martín, Carmen S., Miele, Adriana E., Montagutelli, Xavier, Morcillo, Esteban, Nicoletti, Rosario, Niehof, Monika, O’Toole, Ronan, Ohtomo, Toshihiko, Oster, Henrik, Palma, Jose-Alberto, Paterson, Russell, Peifer, Mark, Portilla, Maribel, Portillo, M. C., Pritchard, Antonia L., Pusch, Stefan, Raghava, Gajendra P. S., Roberts, Nicola J., Ross, Kehinde, Schuele, Birgitt, Sergeant, Kjell, Shen, Jun, Stella, Alessandro, Sukocheva, Olga, Uversky, Vladimir N., Vanneste, Sven, Villet, Martin H., Viveiros, Miguel, Vorholt, Julia A., Weinstock, Christof, Yamato, Masayuki, Zabetakis, Ioannis, Zhao, Xin, Ziegler, Andreas, Aizat, Wan M., Atlas, Lauren, Bridges, Kristina M., Chakraborty, Sayan, Deschodt, Mieke, Domingues, Helena S., Esfahlani, Shabnam S., Falk, Sebastian, Guisado, J. L., Kane, Nolan C., Kueberuwa, Gray, Lau, Colleen L., Liang, Dai, Liu, Enwu, Luu, Andreas M., Ma, Chuang, Ma, Lisong, Moyer, Robert, Norris, Adam D., Panthee, Suresh, Parsons, Jerod R., Peng, Yousong, Pinto, Inês Mendes, Reschke, Cristina R., Sillanpää, Elina, Stewart, Christopher J., Uhle, Florian, Yang, Hui, Zhou, Kai, Zhu, Shu, Ashry, Mohamed, Bergsland, Niels, Berthold, Maximilian, Chen, Chang-Er, Colella, Vito, Cuypers, Maarten, Eskew, Evan A., Fan, Xiao, Gajda, Maksymilian, Gonzálezlez-Prendes, Rayner, Goodin, Amie, Graham, Emily B., Groen, Ewout J. N., Gutiérrez-Sacristán, Alba, Habes, Mohamad, Heffler, Enrico, Higginbottom, Daniel B., Janzen, Thijs, Jayaraman, Jayakumar, Jibb, Lindsay A., Jongen, Stefan, Kinyanjui, Timothy, Koleva-Kolarova, Rositsa G., Li, Zhixiu, Liu, Yu-Peng, Lund, Bjarte A., Lussier, Alexandre A., Ma, Liping, Mier, Pablo, Moore, Matthew D., Nagler, Katja, Orme, Mark W., Pearson, James A., Prajapati, Anilkumar S., Saito, Yu, Tröder, Simon E., Uchendu, Florence, Verloh, Niklas, Voutchkova, Denitza D., Abu-Zaid, Ahmed, Bakkach, Joaira, Baumert, Philipp, Dono, Marcos, Hanson, Jack, Herbelet, Sandrine, Hobbs, Emma, Kulkarni, Ameya, Kumar, Narendra, Liu, Siqi, Loft, Nikolai D., Reddan, Tristan, Senghore, Thomas, Vindin, Howard, Xu, Haotian, Bannon, Ross, Chen, Branson, Cheung, Johnny T. 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Subjects: Technology and Engineering, SCIENTIFIC SEARCH, Expert-curated database, Biokemia, solu- ja molekyylibiologia - Biochemistry, cell and molecular biology, Databases, RElevant LIterature SearcH consortium, Medicine and Health Sciences, Biomedical research, benchmarking, Biology, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Settore MED/42 - IGIENE GENERALE E APPLICATA, database, Computer. Automation, Science & Technology, 0804 Data Format, relisch, Scientific research in health sciences, Mathematics and Statistics, litearture search, relisch , database, biomedical research, Biomedical literature, Original Article, RELISH, Mathematical & Computational Biology, RECOMMENDER-SYSTEMS, Life Sciences & Biomedicine, Mathematics, 0807 Library and Information Studies
Abstract: Made available in DSpace on 2020-12-11T01:57:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-10-29 Griffith University Gowonda HPC Cluster Queensland Cyber Infrastructure Foundation Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research. 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Univ Ioannina, Med Sch, Dept Hyg & Epidemiol, Ioannina, Greece Tech Univ Munich, Sch Life Sci Weihenstephan, Maximus von Imhof Forum 3, D-85354 Freising Weihenstephan, Germany Univ Hosp Essen, Inst Transfus Med, Essen, Germany Virginia Commonwealth Univ, Comp Sci, Richmond, VA USA Univ Queensland, Inst Social Sci Res, Brisbane, Qld, Australia Univ Lyon, Ctr Int Rech Infectiol, Lyon, France Griffith Univ, Sch Allied Hlth Sci, Gold Coast, Qld, Australia Univ Melbourne, Dept Biochem & Mol Biol, Parkville, Vic, Australia Indiana Univ Purdue Univ, Dept Biohlth Informat, Sch Informat & Comp, Indianapolis, IN 46202 USA Philipps Univ Marburg, Inst Lung Res, Marburg, Germany Indiana Univ, Dept Biol, Bloomington, IN USA Univ Florida, Oral Biol, Gainesville, FL USA Univ Colorado, Dept Biochem, Boulder, CO 80309 USA Kyoto Univ, Ctr Promot Interdisciplinary Educ & Res, Kyoto, Japan Friedrich Loeffler Inst, Inst Virus Diagnost, Greifswald, Germany Univ Oxford, Dept Zool, Oxford, England Tech Univ 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Spain Council Agr Res & Econ, Res Ctr Olive Citrus & Tree Fruit, Caserta, Italy Fraunhofer Inst Toxicol & Expt Med ITEM, Preclin Pharmacol & Vitro Toxicol, Hannover, Germany Univ Tasmania, Sch Med, Hobart, Tas, Australia Chugai Pharmaceut Co Ltd, Oncol Lifecycle Management Dept, Tokyo, Japan Univ Lubeck, Inst Neurobiol, Lubeck, Germany NYU, Sch Med, Neurol, New York, NY USA Univ Putra Malaysia, Dept Plant Pathol, Seri Kembangan, Malaysia Univ N Carolina, Biol, Chapel Hill, NC 27515 USA Univ Southampton, Fac Hlth Sci, Southampton, Hants, England Univ Highlands & Islands, Genet & Immunol Res Grp, Inverness, Scotland Heidelberg Univ, Inst Pathol, Heidelberg, Germany Indraprastha Inst Informat Technol, Dept Computat Biol, New Delhi, India Glasgow Caledonian Univ, Sch Hlth & Life Sci, Glasgow, Lanark, Scotland Liverpool John Moores Univ, Pharm & Biomol Sci, Liverpool, Merseyside, England Parkinsons Inst & Clin Ctr, Basic Res, Sunnyvale, CA USA Luxembourg Inst Sci & Technol, Environm Res & Innovat, Luxembourg, Luxembourg Univ Wollongong, Sch Comp & Informat Technol, Wollongong, NSW, Australia Univ Bari Aldo Moro, Dept Biomed Sci & Human Oncol, Bari, Italy Flinders Univ S Australia, Coll Nursing & Hlth Sci, Adelaide, SA, Australia Univ S Florida, Mol Med, Tampa, FL USA Univ Texas Dallas, Behav & Brain Sci, Richardson, TX 75083 USA Rhodes Univ, Zool & Entomol, Grahamstown, South Africa Univ Nova Lisboa, Inst Higiene & Med Trop, Lisbon, Portugal Swiss Fed Inst Technol, Inst Microbiol, Zurich, Switzerland Inst Ulm, German Red Cross Blood Serv, Immunohaematol, Ulm, Germany Tokyo Womens Med Univ, Inst Adv Biomed Engn & Sci, Tokyo, Japan Univ Limerick, Biol Sci, Limerick, Ireland McGill Univ, Dept Anim Sci, Montreal, PQ, Canada StatSol, Lubeck, Germany Univ KwaZulu Natal, Sch Math Stat & Comp Sci, Pietermaritzburg, South Africa Univ Kebangsaan Malaysia, Inst Syst Biol INBIOSIS, Bangi, Malaysia NIH, Natl Ctr Complementary & Integrat Hlth, Bldg 10, Bethesda, MD 20892 USA Univ Kansas, Med Ctr, Family Med Res Div, Kansas City, KS 66103 USA ASTAR, Inst Mol & Cell Biol, Multimodal Mol Biol, Singapore, Singapore Univ Leuven, Dept Chron Dis Metab & Ageing, Leuven, Belgium Int Iberian Nanotechnol Lab INL, Braga, Portugal Anglia Ruskin, Comp & Technol, Cambridge, England Max Planck Inst Biochem, Struct Cell Biol, Planegg, Germany Univ Seville, Dept Comp Architecture & Technol, Seville, Spain Univ Colorado, EBIO, Boulder, CO 80309 USA Univ Manchester, Canc Sci, Manchester, Lancs, England Australian Natl Univ, Res Sch Populat Hlth, Canberra, ACT, Australia Singapore MIT Alliance Res & Technol, Biosyst, Singapore, Singapore Australian Catholic Univ, Mary MacKillop Inst Hlth Res, Musculoskeletal Hlth & Ageing Res Program, Melbourne, Vic, Australia Ruhr Univ Bochum, Gen Surg, St Josef Hosp, Bochum, Germany Northwest A&F Univ, Coll Life Sci, Xianyang, Shaanxi, Peoples R China Australian Natl Univ, Res Sch Biol, Div Plant Sci, Canberra, ACT, Australia Battelle Mem Inst, Clin & Nonclin Res, Columbus, OH USA Southern Methodist Univ, Biol Sci, Dallas, TX 75275 USA Teikyo Univ, Inst Med Mycol, Tokyo, Japan Tempus Labs, Bioinformat, Chicago, IL USA Hunan Univ, Coll Biol, Changsha, Hunan, Peoples R China Inst Cochin, Dept Infect Immun & Inflammat, Paris, France Royal Coll Surgeons Ireland, FutureNeuro Res Ctr Physiol & Med Phys, Dublin, Ireland Univ Jyvaskyla, Gerontol Res Ctr, Jyvaskyla, Finland Heidelberg Univ, Dept Anesthesiol, Heidelberg, Germany Penn State Univ, Biol, University Pk, PA 16802 USA Chinese Acad Sci, Inst Microbiol, State Key Lab Microbial Resources, Beijing, Peoples R China Univ Sci & Technol China, Sch Life Sci, Hefei, Anhui, Peoples R China Michigan State Univ, Anim Sci, E Lansing, MI 48824 USA SUNY Buffalo, Jacobs Sch Med & Biomed Sci, Dept Neurol, Buffalo Neuroimaging Anal Ctr, New York, NY USA Univ Rostock, Inst Biol Sci, Rostock, Germany South China Normal Univ, Sch Environm, Environm Res Inst, Guangzhou, Guangdong, Peoples R China Univ Bari, Dept Vet Med, Bari, Italy Radboud Univ Nijmegen, Med Ctr, Primary & Community Care, Nijmegen, Netherlands EcoHlth Alliance, New York, NY USA Mayo Clin, Cardiovasc Dept, Rochester, MN USA Med Univ Silesia, Sch Med Katowice, Dept Epidemiol, Katowice, Poland Univ Lleida, Anim Sci, Lleida, Spain Univ Florida, Coll Pharm, Pharmaceut Outcomes & Policy, Gainesville, FL USA Pacific Northwest Natl Lab, Earth & Biol Sci Directorate, Richland, WA 99352 USA Univ Edinburgh, Ctr Discovery Brain Sci, Edinburgh, Midlothian, Scotland Harvard Med Sch, Dept Biomed Informat, Boston, MA 02115 USA Univ Penn, Radiol, Philadelphia, PA 19104 USA Humanitas Univ & Res Hosp, Asthma & Allergy Unit, Biomed Sci Personalized Med, Rozzano, Italy Australian Natl Univ, Dept Quantum Sci, Canberra, ACT, Australia Carl von Ossietzky Univ Oldenburg, Ecol Genom, Oldenburg, Germany Int Med Univ, Paediat Dent & Orthodont, Kuala Lumpur, Malaysia Univ Ottawa, Sch Nursing, Ottawa, ON, Canada Maastricht Univ, Dept Educ Support, Maastricht, Netherlands Univ Manchester, Math, Manchester, Lancs, England Kings Coll London, Fac Life Sci & Med, Sch Populat Hlth Sci, London, England Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld, Australia Harbin Med Univ, Publ Hlth Sch, Epidemiol, Harbin, Heilongjiang, Peoples R China UiT Arctic Univ Norway, Dept Chem, Tromso, Norway Cornell Univ, Biol Stat & Computat Biol, Ithaca, NY USA East China Normal Univ, Sch Ecol & Environm Sci, Shanghai Key Lab Urban Ecol Proc & Ecorestorat, Shanghai, Peoples R China Johannes Gutenberg Univ Mainz, Fac Biol, Mainz, Germany Univ Massachusetts, Food Sci, Amherst, MA 01003 USA Max Planck Inst Terr Microbiol, Complex Adapt Traits Res Grp, Marburg, Germany NIHR Biomed Res Ctr Resp, Ctr Exercise & Rehabil Sci, Leicester, Leics, England Yale Univ, Dept Internal Med, Sect Endocrinol, New Haven, CT USA Sardar Patel Univ, Dept Biosci, Anand, Gujarat, India Univ Tokyo, Dept Appl Phys, Tokyo, Japan Univ Cologne, Vivo Res Facil ivRF, Cologne Excellence Cluster Cellular Stress Respon, Cologne, Germany Natl Open Univ Nigeria, Dept Publ Hlth Sci, Lagos, Nigeria Univ Hosp Regensburg, Dept Radiol, Regensburg, Germany Natl Univ Singapore, Geog, Singapore, Singapore Alfaisal Univ, Coll Med, Riyadh, Saudi Arabia Abdelmalek Essaadi Univ, Fac Sci & Techn Tangier, Biomed Genom & Oncogenet Res Lab, Tetouan, Morocco Tech Univ Munich, Fac Sport & Hlth Sci, Exercise Biol Grp, Munich, Germany Univ Santiago de Compostela, Dept Psicoloxia Social Basica & Metodoloxia, Galiza, Spain Griffith Univ, Signal Proc Lab, Brisbane, Qld, Australia Univ Ghent, Dept Neurol, Ghent, Belgium Ghent Univ Hosp, Ghent, Belgium Univ Ghent, Fac Vet Med, Merelbeke, Belgium Albert Einstein Coll Med, Inst Clin & Translat Res, New York, NY USA Anglia Ruskin Univ, Fac Med Sci, Cambridge, England Peking Univ, Coll Chem & Mol Engn, Beijing, Peoples R China Herlev & Gentofte Hosp, Dept Dermatol & Allergy, Hellerup, Denmark Lady Cilento Childrens Hosp, Med Imaging & Nucl Med, Brisbane, Qld, Australia Univ Gambia, Sch Med & Allied Hlth Sci, Nursing & Reprod Hlth, Brikama, Gambia Univ Sydney, Woolcock Inst Med Res, Sydney, NSW, Australia Wayne State Univ, Comp Sci, Detroit, MI USA Aberdeen Royal Infirm, Otolaryngol, Aberdeen, Scotland Univ Toronto, Lab Med & Pathobiol, Toronto, ON, Canada Chinese Univ Hong Kong, Inst Ageing, Hong Kong, Peoples R China Univ Nebraska Med Ctr, Emergency Med, Omaha, NE USA Univ Florida, Coll Med, Pathol, Gainesville, FL USA Univ Texas MD Anderson Canc Ctr, Radiat Oncol, Houston, TX 77030 USA Univ Pisa, Translat Res NTMS, Pisa, Italy Magna Grecia Univ, Clin & Expt Med, Catanzaro, Italy Univ Vermont, Larner Coll Med, Pediat, Burlington, VT USA Sun Yat Sen Univ, Canc Ctr, Diagnost & Intervent Ultrasound, Guangzhou, Guangdong, Peoples R China Fudan Univ, Inst Brain Sci, Shanghai, Peoples R China Shanxi Agr Univ, Coll Agron, Jinzhong, Shanxi, Peoples R China Univ Toronto, Inst Med Sci, Toronto, ON, Canada Univ Adelaide, ARCPOH, Adelaide, SA, Australia Pelita Harapan Univ, Fac Med, Cardiol & Vasc Med, Tangerang, Indonesia Inst Mental Hlth, Res Div, Singapore, Singapore UCL, MRC Clin Trials Unit, London, England Univ Padua, Dept Philosophy Sociol Educ & Appl Psychol FISPPA, Padua, Italy Univ Lubeck, Dept Psychiat & Psychotherapy, Lubeck, Germany Dalian Univ Technol, Ctr Mol Med, Dalian, Liaoning, Peoples R China Tianjin United Family Healthcare, Reprod Med, Tianjin, Peoples R China Univ Autonoma Barcelona, Dept Engn Quim Biol & Ambiental, Barcelona, Spain Sao Paulo State Univ UNESP, Dept Anim Sci, Sao Paulo, Brazil Helmholtz Zentrum Munchen, Inst Computat Biol, Canc Syst Biol, Ingolstadter Land Str 1, D-85764 Munich, Germany Univ Tokyo, Dept Cardiovasc Med, Tokyo, Japan Sao Paulo State Univ, Vet Clin, Sao Paulo, Brazil Zhejiang Univ, Inst Biotechnol, Hangzhou, Zhejiang, Peoples R China Aarhus Univ, Dept Mol Biol & Genet, Aarhus, Denmark Univ Manchester, St Marys Hosp, Maternal & Fetal Hlth, Manchester, Lancs, England Univ New Mexico, Internal Med, Albuquerque, NM 87131 USA Mayo Clin, Div Biomed Stat & Informat, Jacksonville, FL 32224 USA King Saud Univ, Plant Prod, Riyadh, Saudi Arabia Polish Acad Sci, Inst Genet & Anim Breeding, Dept Mol Biol, Warsaw, Poland Queensland Univ Technol, Optometry & Vis Sci, Brisbane, Qld, Australia Univ Nottingham, Sch Life Sci, Nottingham, England Canc Council Queensland, Canc Res Ctr, Brisbane, Qld, Australia Umea Univ, Dept Chem, Umea, Sweden Publ Hlth England, Ctr Radiat Chem & Environm Hazards, Bristol, Avon, England Univ Campania L Vanvitelli, DISTABIF, Caserta, Italy Bartshealth, Obstet & Gyanecol, London, England Univ Clermont Auvergne, GReD Lab, Clermont Ferrand, France INRA Abeilles & Environm, Avignon, France Queensland Univ Technol, Sch Publ Hlth & Social Work, Brisbane, Qld, Australia Univ Penn, Psychiat, Philadelphia, PA 19104 USA Novosibirsk State Univ, Res Inst Physiol & Basic Med, Novosibirsk, Russia UCL, Dept Chem, London, England La Trobe Univ, Anim Plant & Soil Sci, Melbourne, Vic, Australia Univ Arizona, Epidemiol & Biostat, Tucson, AZ USA Univ Groningen, Univ Med Ctr Groningen, ERIBA, Groningen, Netherlands Univ Gothenburg, Inst Clin Sci, Dept Radiat Phys, Gothenburg, Sweden SUNY Upstate Med Univ, Biochem & Mol Biol, Syracuse, NY 13210 USA Fundacao Oswaldo Cruz, Ctr Pesquisas Goncalo Moniz, Salvador, Bahia, Brazil Inst Environm Sci & Res ESR, Food Water & Environm Microbiol, Christchurch, New Zealand Univ Otago, Food Sci, Dunedin, New Zealand Florida Atlantic Univ, Biomed Sci, Boca Raton, FL 33431 USA Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia Univ Hosp Wurzburg, Inst Clin Neurobiol, Wurzburg, Germany Inst Trop Med, Publ Hlth, Antwerp, Belgium Univ Thessaly, Sch Hlth Sci, Fac Med, Dept Rheumatol & Clin Immunol, Larisa, Greece Univ Basel, UZB Univ Ctr Dent Med, Dept Orthodont & Pediat Dent, Basel, Switzerland Sorbonne Univ, Museum Natl Hist Nat, Inst Systemat Evolut Biodiversite ISYEB, MNHN,CNRS,UMR 7205,EPHE, Paris, France CNRS, Inst Adv Biosci, Paris, France Univ Western Australia, Sch Mol Sci, Perth, WA, Australia Univ Ft Hare, Biochem & Microbiol, Alice, South Africa Univ Tubingen, Phys, Tubingen, Germany Griffith Univ, Sch Environm & Sci, Brisbane, Qld, Australia Philosoph Theol Hsch Vallendar, Stat & Standardised Methods, Vallendar, Germany Imperial Coll London, Life Sci, London, England Univ Adelaide, Adelaide Med Sch, Adelaide, SA, Australia Univ Nebraska Med Ctr, Dept Pharmacol & Expt Neurosci, Omaha, NE USA Technol Univ Dublin, FOCAS Res Inst, Dublin, Ireland INSERM, Natl Inst Hlth & Med Res, Canc Res Ctr Toulouse, Paris, France Univ Santiago de Compostela, Dept Bioloxia Func, Grp BRAINSHARK, Galiza, Spain Univ Nebraska, Biol, Kearney, NE USA Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona, Spain Univ Pisa, Chem & Ind Chem, Pisa, Italy Univ Manchester, Wellcome Trust Ctr Cell Matrix Res, Manchester, Lancs, England Univ Montpellier, CNRS, Inst Human Genet, Montpellier, France Czech Acad Sci, Inst Organ Chem & Biochem, Prague, Czech Republic CSIC, Natl Ctr Biotechnol CNB, Computat Syst Biol Grp, Madrid, Spain Natl Cheng Kung Univ, Dept Biochem & Mol Biol, Tainan, Taiwan Harvard Med Sch, Schepens Eye Res Inst, Ophthalmol, Boston, MA 02115 USA Lanzhou Univ, Hosp 2, Dept Gen Surg, Lanzhou, Gansu, Peoples R China Univ Technol Sydney, Sch Life Sci, Sydney, NSW, Australia JT Chen Clin, Gynecol, Tokyo, Japan Univ Western Australia, Sch Agr & Environm, Perth, WA, Australia Beijing Normal Univ, Fac Geog Sci, Beijing, Peoples R China Univ Missouri, Elect Engn & Comp Sci, Columbia, MO USA Vrije Univ Amsterdam Med Ctr, Amsterdam Publ Hlth Res Inst, Dept Publ & Occupat Hlth, Amsterdam, Netherlands Semmelweis Univ, Med Biochem, Budapest, Hungary Queen Elizabeth Hosp, Dept Clin Oncol, Hong Kong, Peoples R China Univ Pittsburgh, Chem, Pittsburgh, PA USA GB Pant Inst Post Grad Med Educ & Res, Neurol, New Delhi, India Univ Copenhagen, Vet & Anim Sci, Copenhagen, Denmark Univ Palermo, Biomed Dept Internal & Specialist Med DIBIMIS, Sect Endocrinol, Palermo, Italy UCL, NPP, London, England Univ Florida, Microbiol & Cell Sci, Gainesville, FL USA Univ Salford, Sch Hlth Sci, Manchester, Lancs, England Cardiff Univ, Inst Med Genet, Cardiff, S Glam, Wales INSERM, ICO Canc Ctr, Angers, France Univ Colombo, Fac Med, Microbiol, Colombo, Sri Lanka Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing, Peoples R China Univ Porto, Fac Pharm, Porto, Portugal Univ Nottingham, Div Primary Care, Nottingham, England Univ Illinois, Pharm Syst Outcomes & Policy, Chicago, IL USA Pontificia Univ Catolica Goias, Escola Ciencias Agr & Biol, Goiania, Go, Brazil China Japan Friendship Hosp, Dept Oncol, Beijing, Peoples R China Boston Univ, Chem, Boston, MA 02215 USA Amer Univ, Environm Sci, Washington, DC 20016 USA Carleton Univ, Neurosci, Ottawa, ON, Canada Univ Regina, Chem & Biochem, Regina, SK, Canada Univ Montreal, 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Univ Georgia, Epidemiol, Athens, GA 30602 USA Univ Freiburg, Med Ctr, Dept Plast & Hand Surg, Freiburg, Germany Sidra Med, Res, Doha, Qatar Rostock Univ, Med Ctr, Dept Oral Maxillofacial & Plast Surg, Rostock, Germany Harvard Med Sch, Brigham & Womens Hosp, Emergency Med, Boston, MA 02115 USA AgResearch, Forage Sci, Palmerston North, New Zealand Univ Calif Los Angeles, Med, Los Angeles, CA USA Arizona State Univ, Biodesign Inst, Virginia G Piper Ctr Personalized Diagnost, Tempe, AZ USA Sheffield Hallam Univ, Res Inst, Mat & Engn, Sheffield, S Yorkshire, England Aneurin Bevan Univ Healthboard, Resp Med, Newport, Shrops, England Univ Calif San Francisco, Neurol Surg, San Francisco, CA 94143 USA Univ Western Australia, UWA Dent Sch, Perth, WA, Australia Fordham Univ, Biol Sci, Bronx, NY 10458 USA Univ Helsinki, Inst Biotechnol, Helsinki, Finland Fujian Normal Univ, Coll Life Sci, Fuzhou, Fujian, Peoples R China Univ Fukui, Dept Frontier Fiber Technol & Sci, Fukui, Japan Univ Southampton, Fac Med, Clin & Expt Sci, Southampton, Hants, England Univ Urbino, Dept Biomol Sci, Urbino, Italy Osped San Luigi, Allergol Unit, Turin, Italy Muljibhai Patel Urol Hosp, Dept Urol, Nadiad, Gujarat, India Univ Granada, Stratig & Paleontol, Granada, Spain Massey Univ, Sch Vet Sci, Auckland, New Zealand CNR, High Performance Comp & Networking Inst, Naples, Italy Univ Childrens Hosp Zurich, Div Metab, Zurich, Switzerland Univ Childrens Hosp Zurich, Childrens Res Ctr, Zurich, Switzerland Univ Melbourne, Biochem & Mol Biol, Parkville, Vic, Australia Inst Pasteur, Leptospirosis Res & Expertise Unit, Noumea, New Caledonia Tsinghua Univ, Sch Life Sci, Beijing, Peoples R China Cheikh Anta Diop Univ UCAD, Sci Fac, Biol Anim Dept, Dakar, Senegal Providence Portland Med Ctr, Earle A Chiles Res Inst, Portland, OR USA Agr & Agri Food Canada, Lacombe Res & Dev Ctr, Lacombe, AB, Canada Alberta Innovates, Performance Management & Evaluat, Edmonton, AB, Canada Univ Malaga, CSIC, Inst Hortofruticultura Subtrop Mediterranea La Ma, IHSM,UMA, Malaga, Spain James Cook Univ, Coll Publ Hlth Med & Vet Sci, Cairns, Qld, Australia European Commiss, Joint Res Ctr, Ispra, Italy Univ Montpellier, Montpellier, France CSIRO, Floreat, WA, Australia Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangzhou, Guangdong, Peoples R China Vanderbilt Univ, Pharmacol, 221 Kirkland Hall, Nashville, TN 37235 USA RIKEN, KFU RIKEN Translat Genom Unit, Yokohama, Kanagawa, Japan Univ Tubingen, Neurobiol Vocal Commun, Tubingen, Germany Univ Colorado, UCCS Ctr Biofrontiers Inst, Colorado Springs, CO 80907 USA Fred Hutchinson Canc Ctr, Div Basic Sci, Seattle, WA USA Univ Geneva, Fac Med, Primary Care Unit, Geneva, Switzerland Ernst Moritz Arndt Univ Greifswald, Dept Mol Genet & Infect Biol, Greifswald, Germany East China Univ Sci & Technol, Dept Fine Chem, Shanghai, Peoples R China Ohio State Univ, Surg, Columbus, OH 43210 USA Oragenics, R&D, Tampa, FL USA Natl Environm Agcy, Environm Hlth Inst, Singapore, Singapore Friedrich Loeffler Inst, Inst Diagnost Virol, Greifswald, Germany Queen Elizabeth Hosp, Oncol, Woodville, SA, Australia USDA, Emerging Pests & Pathogens Res Unit, Ithaca, NY USA Univ Freiburg, Med Ctr, Dept Neurosurg, Epilepsy Ctr, Freiburg, Germany Univ Hong Kong, Fac Educ, Informat & Technol Studies, Hong Kong, Peoples R China Univ Tokyo, Grad Sch Agr & life Sci, Agr & Environm Biol, Tokyo, Japan Univ Pittsburgh, Dept Med, Pittsburgh Heart Lung & Blood Vasc Med Inst, Pittsburgh, PA USA Guys & St Thomas NHS Fdn Trust, Directorate Transplant Renal & Urol, London, England Univ Sarajevo, Clin Ctr, Clin Heart Blood Vessel & Rheumat Dis, Sarajevo, Bosnia & Herceg Univ Kent, Sch Math Stat & Actuarial Sci, Canterbury, Kent, England Tokyo Inst Technol, Dept Life Sci & Technol, Tokyo, Japan Univ Appl Sci Munich, Laser Ctr Dept Appl Sci & Mechatron, Munich, Germany CIC NanoGUNE, Nanodevices, San Sebastian, Spain Vrije Univ Amsterdam Med Ctr, Gynaecol, Amsterdam, Netherlands Cardiff Univ, Med Sch, Div Populat Med, Cardiff, S Glam, Wales Karolinska Inst, Dept Med, Solna, Sweden Natl Inst Genet, Ctr Informat Biol, Mishima, Shizuoka, Japan Murdoch Univ, Harry Perkins Inst Med Res, Perth, WA, Australia Univ Limerick, Phys Educ & Sport Sci, Limerick, Ireland Ruhr Univ Bochum, Campus Clin Gynecol, Univ Str, Bochum, Germany Southwest Med Univ, Sch Publ Hlth, Epidemiol & Biostat, Luzhou, Sichuan, Peoples R China Beijing Canc Hosp, Minist Educ Beijing, Key Lab Carcinogenesis & Translat Res, Ctr Mol Diagnost, Beijing, Peoples R China Chinese Acad Sci, Chengdu Inst Biol, Herpetol Dept, Chengdu, Sichuan, Peoples R China Key Lab Nano Biol Effects & Safety, Beijing, Peoples R China NIBR, PK Sci, Basel, Switzerland Daejeon St Marys Hosp, Pain Ctr, Daejeon, South Korea Univ Western Ontario, Sch Hlth Studies, London, ON, Canada Univ Aberdeen, Hlth Psychol Grp, Aberdeen, Scotland Univ Colorado, Anesthesiol, Anschutz Med Campus, Boulder, CO 80309 USA Univ Antwerp, UZA Antwerp Univ Hosp, Crit Care Med, Edegem, Belgium Aarhus Univ Hosp, Endocrinol, Aarhus, Denmark Univ Pretoria, Ctr Transport Dev, Ind & Syst Engn, Pretoria, South Africa Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA Pontificia Univ Catolica Goias, Med Pharmaceut & Biomed Sci Sch, Goiania, Go, Brazil Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Div Cardiovasc Med, Stockholm, Sweden UCL, Clin Educ & Hlth Psychol, London, England KRIBB, Dev & Differentiat Res Ctr, Daejeon, South Korea Univ dArtois, Lab Barriere Hematoencephal, Arras, France AstraZeneca, IMED Biotech Unit, Discovery Sci, Quantitat Biol, Cambridge, England Pacific Northwest Natl Lab, Environm Mol Sci Lab, Richland, WA 99352 USA Coventry Univ, Appl Maths Res Ctr, Stat Phys Grp, Coventry, W Midlands, England Wilton Ctr, Invista Performance Technol, Cleveland, England Thunen Inst Forest Genet, Genome Res, Grosshansdorf, Germany Lebanese Amer Univ, Nat Sci, Byblos, Lebanon Takeda, Evidence & Value Generat, Osaka, Japan King Abdullah Int Med 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Univ Calif Los Angeles, Sch Dent, Sect Periodont, Los Angeles, CA 90024 USA Aalborg Univ Hosp, Dept Clin Biochem, Aalborg, Denmark Manipal Acad Higher Educ, Pharm Practice, Manipal, Karnataka, India Univ Tokyo, Inst Med Sci, Dept Radiol, Tokyo, Japan Cukurova Univ, Family Med, Fac Med, Adana, Turkey Catholic Univ Korea, Coll Med, Dept Humanities & Social Med, Seoul, South Korea Univ Ghent, Food Technol Safety & Hlth, Ghent, Belgium UNSW Sydney, Sch Biol Earth & Environm Sci BEES, Sydney, NSW, Australia St Vincent Shoulder & Sports Clin, Res Unit, Vienna, Austria Cornell Univ, Biomed Engn, Ithaca, NY USA Leibniz Inst Plant Genet & Crop Plant Res IPK, Res Grp Bioinformat & Informat Technol, Gatersleben, Germany Univ Europea Madrid, Sch Doctoral Studies, Madrid, Spain CSIRO Mfg, Biomed Mfg, Melbourne, Vic, Australia Depaul Univ, Biol Sci, Chicago, IL 60604 USA Konkuk Univ, Dept Anim Sci & Technol, Seoul, South Korea Chang Gung Univ, Grad Inst Med Mechatron, Taoyuan, Taiwan Korea Univ, 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Germany Cardiff Univ, Sch Psychol, Cardiff, S Glam, Wales Imperial Coll London, Chem Engn, London, England Lund Univ, Skane Univ Hosp, Clin Sci, Malmo, Sweden Sahlgrens Acad, Inst Clin Sci, Dept Mol & Clin Med, Gothenburg, Sweden Univ Cent Lancashire, Sch Pharm & Biomed Sci, Preston, Lancs, England Hosp Univ Doctor Peset, Psychiat & Clin Psychol, Valencia, Spain Ctr Biol Mol Severo Ochoa, Genome Dynam & Funct, Madrid, Spain Unvivers Hosp Lille, Dept Intens Care, Lille, France Kansai Med Univ, Surg, Osaka, Japan Univ Toulouse, Inst Natl Polytech Toulouse, Ecole Natl Super Agron Toulouse, Lab Genom & Biotechnol Fruit, Toulouse, France UiT Arctic Univ Norway, Inst Psychol, Tromsto, Norway Queens Univ, Ctr Publ Hlth, Belfast, Antrim, North Ireland Univ Manchester, Ctr Primary Care & Hlth Serv Res, Manchester, Lancs, England Griffith Univ, Menzies Hlth Inst, Gold Coast, Qld, Australia Anglia Ruskin Univ, FHSCE, Cambridge, England Univ Lleida, Dept Expt Med, Lleida, Spain NIEHS, Biomol Screening Branch, Div Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA Albany Med Coll, Immunol & Microbial Dis, Albany, NY 12208 USA Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia Univ Kent, Sch Biosci, Canterbury, Kent, England Univ Bourgogne Franche Comte, INSERM, LNC, UMR 1231, Besancon, France Ritsumeikan Univ, Coll Life Sci, Dept Biotechnol, Shiga, Japan Kent State Univ, Biol Sci, Kent, OH 44242 USA Natl Inst Infect Dis, Dept Safety Res Blood & Biol Prod, Tokyo, Japan European Inst Marine Studies, Lab Microbiol Extreme Environm, Plouzane, France Univ Iowa, Dept Pharmacol, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA Natl Univ Singapore, Biol Sci, Singapore, Singapore Conservatoire Natl Arts & Metiers, Lab GBA, EA4627, Paris, France Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA Lomonosov Moscow State Univ, Belozersky Inst Physicochem Biol, Moscow, Russia Jikei Univ, Sch Med, Dept Mol Biol, Tokyo, Japan Univ South Wales, Genom & Computat Biol, Treforest, Wales Duke Univ, Med Ctr, Obstet & Gynecol, Durham, NC USA Univ Technol Sydney, Climate Change Cluster, Sydney, NSW, Australia Nagoya Univ, Grad Sch Med, Dept Radiol, Nagoya, Aichi, Japan Western Sydney Univ, Sch Sci & Hlth, Sydney, NSW, Australia TEI Epirus, Dept Speech & Language Therapy, Ioannina, Greece Indiana Univ Purdue Univ, Orthopaed Surg, Indianapolis, IN 46202 USA Oniris, Vet Pathol, Nantes, France Royal Vet Coll, Pathobiol & Populat Sci, Hatfield, Herts, England Univ Ghent, Lab Pharmaceut Biotechnol, Ghent, Belgium Norwegian Inst Nat Res, Terr Ecol, Trondheim, Norway Univ Calif Merced, Mol & Cell Biol, Merced, CA USA Univ Dublin, Trinity Coll Dublin, Sch Engn, Ctr Transport Res, Dublin, Ireland Lund Univ, Inst Clin Sci, Nephrol, Malmo, Sweden Univ Birmingham, Mech Engn, Birmingham, W Midlands, England Lund Univ, Inst Clin Sci, OB GYN, Lund, Sweden Fdn Jimenez Diaz Hosp, Nephrol & Hypertens, Madrid, Spain Queensland Univ Technol, Sch Chem Phys & Mech Engn, Brisbane, Qld, Australia Otto von Guericke Univ, Psychol, Magdeburg, Germany Univ Med Ctr Gottingen, Dept Expt Neurodegenerat, Gottingen, Germany Harvard Med Sch, Spaulding Rehabil Hosp, Phys Med & Rehabil, Boston, MA 02115 USA Quadram Inst Biosci, Sci Operat, Norwich, Norfolk, England Ostbayer Tech Hsch Regensburg OTH Regensburg, Regensburg Med Image Comp ReMIC, Regensburg, Germany Deakin Univ, Fac Arts & Educ, Melbourne, Vic, Australia Univ Warwick, Warwick Med Sch, Coventry, W Midlands, England INSERM, Natl Inst Hlth & Med Res, Biochem & Mol Biol, Paris, France Univ Liege, Tax Inst, Liege, Belgium Univ Leeds, Sch Mol & Cellular Biol, Leeds, W Yorkshire, England IRCCS Ist Giannina Gaslini, UOC Genet Med, Genoa, Italy Res Diets Inc, Sci, New Brunswick, NJ USA Univ Perugia, Dept Phys & Geol, Perugia, Italy Walter Reed Natl Mil Med Ctr, Cellular Immunol, Bethesda, MD USA Univ Fed Santa Catarina, Biol Sci Ctr, Microbiol Immunol & Parasitol Dept, Florianopolis, SC, Brazil Univ Edinburgh, Royal Infirm, Ctr Liver & Digest Disorders, Edinburgh, Midlothian, Scotland Orion Pharma, Crit Care Proprietary Prod Div, Espoo, Finland MIT, Dept Civil & Environm Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA Univ Turin, Dept Vet Sci, Turin, Italy Univ G dAnnunzio, Dept Psychol Hlth & Territorial Sci, Chieti, Italy NYU, Sch Med, OB GYN, New York, NY USA Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland Univ Turku, Dept Biol, Turku, Finland Tech Univ Berlin, Bioanalyt, Berlin, Germany Univ Goettingen, Inst Phys Biophys 3, Gottingen, Germany Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Translat Res Adv Therapeut & Innovat Oncol TRACTI, Houston, TX 77030 USA Univ Liege, Life Sci, Liege, Belgium Tarbiat Modares Univ, Fac Med Sci, Dept Toxicol, Tehran, Iran ARS, USDA, Stoneville, MS USA Univ Regensburg, RCI Regensburg Ctr Intervent Immunol, Regensburg, Germany Univ Nottingham, Sch Psychol, Nottingham, England NIH, Pathol Lab, Bethesda, MD 20892 USA Univ Carlos III Madrid, Elect Engn, Madrid, Spain Inst Med Mol, Chem Biol, Lisbon, Portugal Univ Costa Rica, CIET, San Jose, Costa Rica Univ Stavanger, Fac Hlth Sci, Stavanger, Norway Erasmus MC, Urol, Rotterdam, Netherlands Univ Edinburgh, Sch Biol Sci, Edinburgh, Midlothian, Scotland German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Inst Bioinformat & Syst Biol IBIS, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany Leiden Univ, Huygens Kamerlingh Onnes Lab, Leiden, Netherlands Univ Vienna, Nutr Sci, Vienna, Austria Kolling Inst Med Res, Med, St Leonards, NSW, Australia Johns Hopkins Sch Med, Biol Chem, Baltimore, MD USA Univ Montreal, Med Nutr & Microbiome Lab, Montreal, PQ, Canada GlaxoSmithKline, Cell & Gene Therapy, Stevenage, Herts, England Univ Trieste, Life Sci, Trieste, Italy Rhein Westfal TH Aachen, Dept Radiol, Aachen, Germany Univ Duisburg Essen, Univ Hosp Essen, West German Canc Ctr, Dept Med Oncol, Essen, Germany Med Univ Vienna, Obstet & 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Pittsburgh, PA USA Univ Lausanne, Ctr Integrat Genom, Lausanne, Switzerland Univ Queensland, Sch Pharm, Brisbane, Qld, Australia Leibniz Inst Plant Genet & Crop Plant Res IPK Gat, Genebank, Gatersleben, Germany Piramal Imaging, Res & Dev, Berlin, Germany Univ Leeds, Civil Engn, Leeds, W Yorkshire, England Univ Missouri, Chem & Biochem, St Louis, MO 63121 USA US Geol Survey, Coastal & Marine Geol Program, Pacific Coastal & Marine Sci Ctr, Santa Cruz, CA USA Ajinomoto Genet Res Inst, Moscow, Russia Jagiellonian Univ, Fac Biochem Biophys & Biotechnol, Dept Plant Biotechnol, Krakow, Poland Univ Puerto Rico, Engn Sci & Mat, Mayaguez, PR USA Univ Regina, Dept Chem & Biochem, Regina, SK, Canada Argonne Natl Lab, Ctr Nanoscale Mat, 9700 S Cass Ave, Argonne, IL 60439 USA Univ Sunshine Coast, Sunshine Coast Mind & Neurosci Thompson Inst, Sippy Downs, Qld, Australia Chinese Peoples Liberat Army Gen Hosp, Dept Gastroenterol & Hepatol, Beijing, Peoples R China Griffith Univ, Griffith Ctr Social & Cultural Res, Gold Coast, Qld, Australia Tohoku Univ, Inst Dev Aging Canc, Dept Mol Oncol, Sendai, Miyagi, Japan Indiana Univ, Comp Sci, Bloomington, IN USA Fukushima Med Univ, Sch Med, Dept Pulm Med, Fukushima, Japan MEDIVIR AB, Biol, Huddinge, Sweden Western Sydney Univ, Neuroimmunol, Sydney, NSW, Australia Univ Jordan, Nutr & Food Technol, Amman, Jordan Thunen Inst Forest Genet, Fed Res Ctr Rura Areas Forestry & Fisheries, Inst Biodivers, Grosshansdorf, Germany Univ Edinburgh, Inst Cell Biol, Edinburgh, Midlothian, Scotland Univ Edinburgh, Ctr Integrat Physiol, Edinburgh, Midlothian, Scotland Univ Toronto, Struct Genom Consortium, Toronto, ON, Canada Canadian Mem Chiropract Coll, Grad Educ & Res, Toronto, ON, Canada Agilent Technol, R&D, Leuven, Belgium Univ British Columbia, Sch Nursing, Vancouver, BC, Canada Monash Univ, Monash Hlth, Sch Clin Sci, Stroke & Ageing Res,Dept Med, Melbourne, Vic, Australia French Natl Canc Inst, Innovat, Transfer, Biol, Boulogne, France Ludwig Maximilians Univ Munchen, Phys Chem, NanoBioSci, Munich, Germany Bandung Inst Technol, Sch Pharm, Med Chem, Bandung, Indonesia Univ Luxembourg, Life Sci Res Unit, Luxembourg, Luxembourg Lund Univ, Skane Univ Hosp, Dept Gastroenterol, Malmo, Sweden Millennium Hlth, Translat Genet, San Diego, CA USA Aristotle Univ Thessaloniki, Med Dept 2, Clin Res & Evidence Based Med Unit, Thessaloniki, Greece Jan Kochanowski Univ Humanities & Sci, Piotrkow Trybunalski Branch, Dept Psychol, Kielce, Poland McMaster Univ, Engn Phys, Hamilton, ON, Canada Marche Polytech Univ, Dept Agr Food & Environm Sci, Ancona, Italy Kuwait Univ, Fac Med, Microbiol, Kuwait, Kuwait Fujita Hlth Univ, Dept Breast Surg, Toyoake, Aich, Japan North West Reg Spinal Injuries Ctr, Spinal Injuries Ctr, Southport, Merseyside, England Luxembourg Inst Hlth, Competence Ctr Methodol & Stat, Luxembourg, Luxembourg Nestle Inst Hlth Sci SA, Metab Hlth, Ecublens, Vaud, Switzerland Ctr Inflammat Res VIB, Ghent, Belgium Univ Ghent, Dept Biomed Mol Biol, Ghent, Belgium Univ Lisbon, Inst Educ, Curriculo Formacao Prof & Tecnol, Lisbon, Portugal Univ Edinburgh, Ctr Inflammat Res, Edinburgh, Midlothian, Scotland Univ Melbourne, Sch BioSci, Parkville, Vic, Australia Northumbria Univ, Comp & Informat Sci, Newcastle Upon Tyne, Tyne & Wear, England Univ Valencia, Endocrinol, Valencia, Spain INRS, Inst Armand Frappier, Laval, PQ, Canada Univ Laval, INAF, Sch Nutr, Quebec City, PQ, Canada Univ Konstanz, Dept Biol, Constance, Germany Univ Cote dAzur, LAMHESS, Nice, France Scion, Syst Ecol, Christchurch, New Zealand CUNY, Grad Sch Publ Hlth & Hlth Policy, Epidemiol & Biostat, New York, NY 10021 USA Univ Queensland, Sch Dent, Brisbane, Qld, Australia George Inst Global Hlth, Renal & Metab Div, Sydney, NSW, Australia Wuhan Univ, Coll Chem & Mol Sci, Wuhan, Hubei, Peoples R China Griffith Univ, Sch Environm & Sci, Gold Coast, Qld, Australia Univ Minnesota, Radiat Oncol, Minneapolis, MN USA Goethe Univ, Fac Med, Frankfurt, Germany Natl Yunlin Univ Sci & Technol, Dept & Grad Sch Safety & Environm Engn, Touliu, Yunlin, Taiwan Massey Univ, Sch Sport Exercise & Nutr, Auckland, New Zealand Univ Florida, Wildlife Ecol & Conservat, Gainesville, FL USA Bournemouth Univ, Dept Psychol, Poole, Dorset, England Robert Koch Inst, Project Grp P2, Berlin, Germany Univ Edinburgh, MRC Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland Univ Basel, Biozentrum, Basel, Switzerland Univ Wollongong, Sch Med, Wollongong, NSW, Australia Univ Cologne, Inst Human Genet, Cologne, Germany Rural Econ Branch, Econ Res Serv, Washington, DC USA Uivers Bordeaux, CNRS, Inst Neurosci Cognit & Integrat Aquitaine, Bordeaux, France Univ Calif Riverside, Dept Chem & Environm Engn, Riverside, CA 92521 USA Univ Calif Riverside, Mat Sci & Engn Program, Riverside, CA 92521 USA Mackay Med Coll, Dept Med, New Taipei, Taiwan Univ Bern, Div Anim Welf, Bern, Switzerland Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Med Sci, Shanghai, Peoples R China McMaster Univ, Biol, Hamilton, ON, Canada Univ S Florida, Dept Cell Biol Microbiol & Mol Biol, Tampa, FL USA Hacettepe Univ, Inst Canc, Med Oncol, Ankara, Turkey City Univ Hong Kong, Dept Elect Engn, Hong Kong, Peoples R China Natl Taiwan Univ, Dept Entomol, Taipei, Taiwan Chinese Acad Agr Sci, Inst Environm & Sustainable Dev Agr, Ecol Secur, Beijing, Peoples R China Florida State Univ, Inst Mol Biophys, Chem & Biochem, Tallahassee, FL USA Peking Univ, Shenzhen Grad Sch, State Key Lab Chem Oncogen, Lab Computat Chem & Drug Design, Shenzhen, Peoples R China Univ Helsinki, Fac Pharm, Div Pharmaceut Chem & Technol, Drug Res Program, Helsinki, Finland Tohoku Univ, Microbial Biotechnol, Sendai, Miyagi, Japan Tianjin Med Univ, Sch Basical Med Sci, Dept Pharmacol, Tianjin, Peoples R China Dana Farber Canc Inst, Biostat & Computat Biol, Boston, MA 02115 USA Natl Hlth Res Inst, Inst Mol & Genom Med, Zhunan, Taiwan Univ Oxford, Physiol Anat & Genet, Oxford, England George Washington Univ, Phys, Washington, DC USA Univ Nebraska, Sch Biol Sci, Lincoln, NE USA Toronto Gen Hosp, Res Inst, Dept Lab Med & Pathobiol, Toronto, ON, Canada Univ Texas Dallas, Biol Sci, Richardson, TX 75083 USA NYU, Dept Chem, New York, NY USA Shandong Univ, Sch Math & Stat, Jinan, Shandong, Peoples R China Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei, Anhui, Peoples R China Purdue Univ, Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA NIBSC, Adv Therapies, Ridge, Herts, England Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Pulm & Crit Care Med, Shanghai, Peoples R China Charite Med Univ Berlin, Dermatol & Allergy, Berlin, Germany Univ Hosp St Etienne, Hematol, St Etienne, France Inland Norway Univ Appl Sci, Inst Biotechnol, Elverum, Norway Univ Jordan, Pediat, Amman, Jordan Inst Pasteur, Mol Mycol Unit, Paris, France Cardiff Univ, Sch Med, Inst Psychol Med & Clin Neurosci, Med Res Council Ctr Neuropsychiat Genet & Genom, Cardiff, S Glam, Wales Zurich Univ Appl Sci, Social Work, Zurich, Switzerland Jawaharlal Nehru Univ, Sch Life Sci, New Delhi, India Univ Burgundy Franche Comte, LE2I, Dijon, France Univ Roehampton, Life Sci, London, England Ghent Univ Hosp, Gen & HPB Surg, Ghent, Belgium Univ Wurzburg, Insect Fungus Symbiosis Lab, Wurzburg, Germany Radboud Univ Nijmegen, Behav Sci Inst, Nijmegen, Netherlands Fraunhofer WKI, Applicat Ctr HOFZET, Hannover, Germany UCL, Struct & Mol Biol, London, England Univ Amsterdam, Dev Psychol, Amsterdam, Netherlands Aalborg Univ, Hlth Sci & Technol, CNAP, SMI, Aalborg, Denmark VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA Cedars Sinai Med Ctr, Neurosurg, Los Angeles, CA 90048 USA Sun Yat Sen Univ, Sch Data & Comp Sci, Guangzhou, Guangdong, Peoples R China Dezhou Univ, Shandong Prov Key Lab Biophys, Guangzhou, Guangdong, Peoples R China Maison Teledetection, Inst Rech Dev, UMR Espace DEv, Montpellier, France Xiamen Univ, Sch Life Sci, Xiamen, Fujian, Peoples R China Nanjing Univ, Sch Med, Jinling Hosp, Natl Clin Res Ctr Kidney Dis,Dept Med Imaging, Nanjing, Jiangsu, Peoples R China Univ Kent, Sch Social Policy Sociol & Social Res, Canterbury, Kent, England Univ Fed Minas Gerais, Infect Dis & Trop Med, Belo Horizonte, MG, Brazil Univ Minho, Sch Med, Life & Hlth Sci Res Inst ICVS, Braga, Portugal Univ Montreal, Biochim & Med Mol, Montreal, PQ, Canada Johns Hopkins Bloomberg Sch Publ Hlth, Epidemiol, Baltimore, MD USA Max Planck Inst Biol Ageing, Metab & Genet Regulat Ageing, Cologne, Germany Univ Swaziland, Hlth Sci, Kwaluseni, Eswatini Queensland Univ Technol, Inst Future Environm, Brisbane, Qld, Australia Ctr Sci Monaco, Dept Biol Med, Monaco, Monaco HELIOS Hosp, Urol, Bad Saarow Pieskow, Germany Tech Univ Carolo Wilhelmina Braunschweig, Inst Microbiol, Braunschweig, Germany Univ Barcelona, Barcelona Ctr Maternal Fetal & Neonatal Med, Fetal i D Fetal Med Res Ctr, IDIBAPS BCNatal,Hosp Clin, Barcelona, Spain Univ Barcelona, Hosp St Joan de Deu, Barcelona, Spain Friedrich Loeffler Inst, Inst Bacterial Infect & Zoonoses, Jena, Germany Charite Med Univ Berlin, Neurol, Berlin, Germany Dublin City Univ, Natl Inst Cellular Biotechnol, Mol Therapeut Canc Ireland, Dublin, Ireland Schoen Clin Roseneck, Prien Am Chiemsee, Germany Univ Med Ctr Hamburg Eppendorf, Inst Sex Res & Forens Psychiat, Hamburg, Germany Nankai Univ, Sch Math Sci, Tianjin, Peoples R China Nankai Univ, LPMC, Tianjin, Peoples R China Univ Oxford, Oncol, Oxford, England Royal Holloway Univ London, Class, Egham, Surrey, England Cornell Univ, Clin Sci, Ithaca, NY USA Univ KwaZulu Natal, Pharmaceut Chem, Westville Campus, Durban, South Africa Royal Coll Surgeons Ireland, Med, Dublin, Ireland Univ Oslo, Dept Immunol, Oslo, Norway Bermuda Inst Ocean Sci, Marine Nitrogen Cycling Lab, St Georges, Bermuda Kanazawa Univ, Inst Liberal Arts & Sci, Kanazawa, Ishikawa, Japan World Hlth Org Reg Off Africa, Brazzaville, Rep Congo Univ Hosp BesanCon, Infect Control Dept, Besancon, France Galapagos NV, Clin Dev, Mechelen, Belgium Univ Tasmania, Integrated Marine Observing Syst, Hobart, Tas, Australia Georg August Univ Gottingen, Albrecht von Haller Inst Plant Sci, Dept Systemat Biodivers & Evolut Plants, Gottingen, Germany Univ Occupat & Environm Hlth, Dept Psychiat, Fukuoka, Fukuoka, Japan IMDEA Food, Program Precis Nutr & Aging, Madrid, Spain Radboud Univ Nijmegen, Med Sch, IQHealthcare, Nijmegen, Netherlands Maastricht Univ, Dept Cardiovasc Surg, Maastricht, Netherlands German Diabet Ctr, Inst Clin Biochem & Pathobiochem, Dusseldorf, Germany Juntendo Univ, Grad Sch Med, Dept Radiol, Tokyo, Japan Deakin Univ, Sch Informat Technol, Melbourne, Vic, Australia Max Planck Inst Eusenforschung, Dept Interface Chem & Surface Sci, Dusseldorf, Germany Edge Hill Univ, Dept Psychol, Ormskirk, England Aga Khan Univ, Psychiat, Karachi, Pakistan KRIBB, Korean Bioinformat Ctr, Seoul, South Korea Cardinal Hlth Specialty Solut, Hlth Econ & Outcomes Res, Dallas, TX USA Klinikum Univ Munchen, Div Clin Pharmacol, Munich, Germany Univ Pittsburgh, Neurol Surg, Pittsburgh, PA USA Rhein Westfal TH Aachen, Dept Child & Adolescent Psychiat Psychosomat & Ps, Aachen, Germany Univ Copenhagen, Inst Mol & Cellular Biol, Copenhagen, Denmark St Jude Childrens Res Hosp, Struct Biol, 332 N Lauderdale St, Memphis, TN 38105 USA Royal Shrewsbury Hosp, Colorectal Surg, Shrewsbury, Salop, England Univ Nottingham, Fac Med & Hlth Sci, Nottingham, England Karolinska Inst, Dept Physiol & Pharmacol, Solna, Sweden Chinese Acad Sci, Changchun Inst Appl Chem, State Key Lab Electroanalyt Chem, Jilin, Jilin, Peoples R China Univ British Columbia, Pediat, Vancouver, BC, Canada Chinese Acad Agr Sci, State Key Lab Cotton Biol, Res Base Anyang Inst Technol, Cotton Germplasm Resources,Inst Cotton Res, Beijing, Peoples R China Chinese Univ Hong Kong, Anaesthesia & Intens Care, Hong Kong, Peoples R China Univ Macau, ICMS, Zhuhai, Guangdong, Peoples R China North China Elect Power Univ, Sch Renewable Energy, Beijing, Peoples R China Justus Liegbig Univ, Dept Internal Med, Giessen, Germany Aarhus Univ, Biosci, Aarhus, Denmark Univ Dublin, Trinity Coll Dublin, Irish Longitudinal Study Ageing TILDA, Dublin, Ireland Univ Groningen, Univ Med Ctr Groningen, Hematol, Groningen, Netherlands Vrije Univ Amsterdam Med Ctr, Child Neurol, Amsterdam, Netherlands EBI, EMBL, Cambridge, England Max Planck Inst Marine Microbiol, HGF MPG Joint Res Grp Deep Sea Ecol & Technol, Bremen, Germany Max Planck Inst Human Dev, Ctr Adapt Rat, Berlin, Germany King Faisal Univ, Math, Al Hufuf, Saudi Arabia Griffith Univ, Sch Nursing & Midwifery, Gold Coast, Qld, Australia Iowa State Univ, Roy J Carver Dept Biochemsitry Biophys & Mol Biol, Ames, IA USA Delft Univ Technol, Fac Mech Maritime & Mat Engn, Engn Thermodynam Proc & Energy Dept, Leeghwaterstr 39, NL-2628 CB Delft, Netherlands Univ Nebraska Med Ctr, Coll Allied Hlth Profess, Cytotechnol Educ, Omaha, NE USA Shinko Mem Hosp, Dept Cardiovasc Med, Kobe, Hyogo, Japan Imperial Coll London, Mat, London, England Tech Univ Munich, Dept Surg, Munich, Germany Chinese Acad Agr Sci, Res Inst Pomol, Minist Agr, Lab Qual & Safety Risk Assessment Fruit Xingcheng, Shenyang, Liaoning, Peoples R China James Madison Univ, Commun Sci & Disorders, Harrisonburg, VA 22807 USA Univ Hosp Ulm, Inst Orthopaed Res & Biomech, Ulm, Germany Univ Essex, Sch Hlth & Social Care, Colchester, Essex, England Alpha Altis, Res Serv, Nottingham, England Erasmus MC, Med Oncol, Rotterdam, Netherlands Fed Univ Oye, Dept Ind Chem, Ekiti, Nigeria Duke Univ, Med Ctr, Cell Biol, Durham, NC USA Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England Univ Manchester, Canc Res UK Manchester Inst, Manchester, Lancs, England Helsinki Univ Hosp, Childrens Hosp, Helsinki, Finland Univ Aveiro, CESAM Ctr Environm & Marine Studies, Dept Biol, Aveiro, Portugal Univ Botswana, Psychol, Gaborone, Botswana Univ Fed Bahia, Nursing Sch, Salvador, BA, Brazil Queen Mary Univ London, Biol & Expt Psychol, London, England Natl Univ Pharm, Med Chem Dept, Kharkov, Ukraine Univ Bolton, Dept Educ & Psychol, Bolton, England La Trobe Univ, Dept Chem & Phys, Melbourne, Vic, Australia Gen Hosp Northern Theater Command, Dept Gastroenterol, Shenyang, Liaoning, Peoples R China Doctors Hosp, Dept Nephrol, Athens, Greece Univ Hosp Essen, Pediat 3, Essen, Germany Imperial Coll London, Infect Dis Epidemiol, London, England Sorbonne Univ, Dept Psychiat, Paris, France UNSW Sydney, Educ, Sydney, NSW, Australia Stanford Univ, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA Hannover Med Sch, Clin Laryngol Rhinol & Otol, Hannover, Germany Curtin Univ, Ctr Aboriginal Studies, Perth, WA, Australia Iran Univ Sci & Technol, Biomed Engn Dept, Tehran, Iran Univ Calif San Francisco, Anesthesiol, San Francisco, CA 94143 USA Khalifa Univ Sci & Technol, Mech Engn, Abu Dhabi, U Arab Emirates Univ Florida, Hort Sci, Gainesville, FL USA James Cook Univ, Australian Inst Trop Hlth & Med, Ctr Biodiscovery & Mol Dev Therapeut, Cairns, Qld, Australia Univ Porto, Fac Med, CINTESIS, Porto, Portugal Shaoxing Peoples Hosp, Med Res Ctr, Shaoxing, Zhejiang, Peoples R China NIH, Dept Transfus Med, Bethesda, MD 20892 USA AIIMS, Dept Biotechnol, New Delhi, India Univ Ottawa, Biochem Microbiol & Immunol, Ottawa, ON, Canada Univ Oslo, Inst Clin Med, Div Mental Hlth & Addict, Oslo, Norway Univ Groningen, Univ Med Ctr Groningen, Dept Radiol, Groningen, Netherlands Univ Hong Kong, Sch Nursing, Hong Kong, Peoples R China Tokyo Med Univ, Ibaraki Med Ctr, Urol, Tokyo, Japan Univ Hosp Zurich, Dept Radiat Oncol, Zurich, Switzerland Univ Maryland, Inst Human Virol, Div Immunotherapy, Baltimore, MD 21201 USA Univ Maryland, Dept Surg, Baltimore, MD 21201 USA Stellenbosch Univ, Fac Med & Hlth Sci, Div Mol Biol & Human Genet, Stellenbosch, South Africa China Agr Univ, Coll Biol Sci, Beijing, Peoples R China Osaka Univ, Grad Sch Pharmaceut Sci, Suita, Osaka, Japan Univ Washington, Biochem, Seattle, WA 98195 USA Natl Res Council Italy, Inst Biosci & BioResources, Naples, Italy Univ Lyon, Phys, Lyon, France Univ Basel, Fac Psychol, Ctr Social Psychol, Basel, Switzerland Queen Mary Univ London, Barts Canc Inst, Ctr Mol Oncol, London, England EBI, EMBL, Samples Phenotypes & Ontol Team, Cambridge, England Charles Sturt Univ, Fac Arts & Educ, Bathurst, NSW, Australia Shandong Univ, Helmholtz Inst Biotechnol, Sch Life Sci, State Key Lab Microbial Technol, Jinan, Shandong, Peoples R China Shantou Univ, Dept Biol, Shantou, Guangdong, Peoples R China Shanxi Univ, Inst Biomed Sci, Taiyuan, Shanxi, Peoples R China St Jude Childrens Res Hosp, Computat Biol, 332 N Lauderdale St, Memphis, TN 38105 USA Harbin Med Univ, Coll Bioinformat Sci & Technol, Harbin, Heilongjiang, Peoples R China NIH, Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA Georgia Inst Technol, Dept Biol Sci, Atlanta, GA 30332 USA XtalPi Inc, Cambridge, MA USA Consejo Nacl Invest Cient & Tecn, Partner Inst Max Planck Soc, Inst Invest Biomed Buenos Aires IBioBA, Bioinformat, Buenos Aires, DF, Argentina Univ Sydney, Save Sight Inst, Sydney, NSW, Australia Univ South Australia, Canc Res Inst, Australian Ctr Precis Hlth, Adelaide, SA, Australia Jinan Univ, Inst Life & Hlth Engn, Guangdong Higher Educ Inst, Key Lab Funct Prot Res, Guangzhou, Guangdong, Peoples R China Univ Texas Hlth Sci Ctr Houston, Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA Weill Cornell Med, Dept Microbiol & Immunol, New York, NY USA Guangdong Inst Appl Biol Resources, Biotechnol Lab, Guangzhou, Guangdong, Peoples R China Shandong Normal Univ, Coll Life Sci, Jinan, Shandong, Peoples R China Shandong Univ, Life Sci Dept, Jinan, Shandong, Peoples R China South China Agr Univ, Integrat Microbiol Res Ctr, Guangzhou, Guangdong, Peoples R China Liaoning Acad Agr Sci, Crop Mol Improving Lab, Shenyang, Liaoning, Peoples R China Lawson Hlth Res Inst, Med Biophys, London, ON, Canada Univ Melbourne, Infrastruct Engn, Parkville, Vic, Australia Univ Canberra, Fac Hlth, Canberra, ACT, Australia Univ Cambridge, MRC Cognit & Brain Sci Unit, Cambridge, England Emory Univ, Biostat & Bioinformat, Atlanta, GA 30322 USA Johns Hopkins Sch Med, Anesthesiol & Crit Care Med, Baltimore, MD USA Nottingham Trent Univ, Sch Anim Rural & Environm Sci, Nottingham, England Univ Exeter, Biosci, Exeter, Devon, England Hillingdon Hosp NHS Fdn Trust, London, England Univ Glasgow, MRC CSO Social & Publ Hlth Sci Unit, Glasgow, Lanark, Scotland Natl & Kapodistrian Univ Athens, Evaggelismos Athens Hosp, ICU, Athens, Greece Univ Newcastle, Biol Sci, Callaghan, NSW, Australia Coventry Univ, Fac Hlth & Life Sci, Ctr Innovat Res Life Course, Coventry, W Midlands, England Lausanne Univ Hosp, Serv Endocrinol Diabet & Metab, Lausanne, Switzerland Charles Sturt Univ, Sch Community Hlth, Bathurst, NSW, Australia Queens Univ Belfast, Inst Global Food Secur, Belfast, Antrim, North Ireland Natl Univ Singapore, Inst Policy Studies, Singapore, Singapore Univ Penn, Intitute Med & Engn, Philadelphia, PA 19104 USA Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA Univ Michigan, EECS, Ann Arbor, MI 48109 USA Univ British Columbia, Ctr Blood Res, Vancouver, BC, Canada UiT Arctic Univ Norway, Dept Hlth & Care Sci, Fac Hlth Sci, Tromso, Norway Hosp Clin Porto Alegre, Physiotherapy, Porto Alegre, RS, Brazil Univ Paris 05, Med Sch, Paris, France Chinese Acad Agr Sci, Inst Crop Sci, Natl Key Facil Crop Gene Resources & Genet Improv, Beijing, Peoples R China Univ Ghent, Expt Clin & Hlth Psychol, Ghent, Belgium Indian Inst Adv Res, Bioinformat & Struct Biol, Gandhinagar, Gujart, India Bambino Ges Childrens Res Hosp, Lab Mol Med, Rome, Italy Heidelberg Univ, Ctr Infect Dis Parasitol, Heidelberg, Germany Stanford Univ, Elect Engn, Palo Alto, CA 94304 USA Univ Cadiz, Biol, Andalucia, Spain Mansoura Univ Hosp, Gen Surg, Mansoura, Egypt Inst Pasteur, Virol Pole, Dakar, Senegal Cardiff Univ, Div Canc & Genet, Cardiff, S Glam, Wales Ctr Expertise & Biol Diagnost Cameroon, Food Safety & Environm Microbiol, Yaounde, Cameroon Swiss Fed Labs Mat Sci & Technol, Lab Thin Films & Photovolta, Dubendorf, Switzerland Assiut Univ, Assiut Urol & Nephrol Hosp, Fac Med, Assiut, Egypt UCL, GEE, London, England UCL, IHA, London, England Univ Derby, Univ Derby Online Learning, Derby, England SUNY Stony Brook, Family Populat & Prevent Med, Stony Brook, NY 11794 USA Walter & Eliza Hall Inst Med Res, Mol Med Div, Melbourne, Vic, Australia Newcastle Univ, Northern Inst Canc Res, Newcastle Upon Tyne, Tyne & Wear, England German Ctr Neurodegenerat Dis, Clin Dementia Res, Bonn, Germany Sorbonne Univ, CNRS, UMR 7144, Stn Biol, Paris, France Univ Barcelona, Odontoestomatol, Barcelona, Spain Janelia Res Campus, Comp Sci, Ashburn, VA USA Univ Oxford, Ctr Trop Med & Global Hlth, Oxford, England Univ Bern, ARTORG Ctr Biomed Engn Res, Bern, Switzerland Australian Natl Univ, Eccles Inst Neurosci, John Curtain Sch Med Res, Canberra, ACT, Australia John Innes Ctr, Metab Biol, Norwich, Norfolk, England USDA ARS, Genom & Bioinformat Res Unit, Raleigh, NC 27695 USA Med Univ Graz, Inst Med Informat Stat & Documentat, Holzinger Grp, Graz, Austria Ajou Univ, Pharm, Suwon, South Korea City Univ Hong Kong, Sch Energy & Environm, Hong Kong, Peoples R China Univ British Columbia, Sch Kinseiol, Vancouver, BC, Canada Univ Copenhagen, Marine Biol Sect, Dept Biol, Copenhagen, Denmark Univ Vienna, Dept Commun, Vienna, Austria Univ Dundee, Sch Social Sci, Dundee, Scotland Tech Univ Dresden, Inst Bot, Dresden, Germany Univ Oxford, Div Struct Biol, Oxford, England Natl Univ Hlth Syst, Med, Singapore, Singapore Univ Canterbury, Sch Biol Sci, Christchurch, New Zealand Univ Hosp Southern Denmark, Focused Res Unit Mol Diagnost & Clin Res, Odense, Denmark Univ Oxford, Primary Care Hlth Sci, Oxford, England Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA Adnan Menderes Univ Aydin, Fac Nursing, Dept Publ Hlth Nursing, Aydin, Turkey Oasi Res Inst IRCCS, Dept Neurol IC, Troina, Italy Purdue Univ, Weldon Sch Biomed Engn, W Lafayette, IN 47907 USA Kings Coll London, Kings Ctr Mil Hlth Res, London, England LSHTM, Dept Infect Dis Epidemiol, London, England Leibniz Univ Hannover, BMWZ Organ Chem, Hannover, Germany Xi An Jiao Tong Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Xian, Shaanxi, Peoples R China Univ South Australia, Sch Pharm & Med Sci, Adelaide, SA, Australia Univ Fed Santa Catarina, Dept Phys Educ, Florianopolis, SC, Brazil Southern Med Univ, Nanfang Hosp, Dept Oncol, Guangzhou, Guangdong, Peoples R China Stanford Univ, Hansen Expt Phys Lab, Palo Alto, CA 94304 USA Shenzhen Univ, Affiliated Hosp 1, Shenzhen Peoples Hosp 2, Inst Translat Med, Shenzhen, Guangdong, Peoples R China Univ Hong Kong, Dept Stat & Actuarial Sci, Hong Kong, Peoples R China UCL, Dept Mech Engn, London, England ASTAR, Singapore Immunol Network, Lab Microbial Immun, Singapore, Singapore Cent South Univ, State Key Lab Powder Met, Changsha, Hunan, Peoples R China Univ Aberdeen, Inst Appl Hlth Sci, Aberdeen, Scotland Univ Bridgeport, Biomed Engn, Bridgeport, CT 06601 USA Texas Tech Univ, Hlth Sci Ctr, Pharmaceut Sci, Lubbock, TX 79430 USA Univ Montana, Ecosyst & Conservat Sci, Missoula, MT 59812 USA Univ Goettingen, Dept Syst Neurosci, Gottingen, Germany NHLBI, Lab Syst Genet, Bldg 10, Bethesda, MD 20892 USA Cleveland Clin, Lou Ruvo Ctr Brain Hlth, Imaging, Las Vegas, NV USA Flinders Univ S Australia, Coll Nursing & Hlth Sci, Nutr & Dietet, Adelaide, SA, Australia Univ Padua, Dept Math, Padua, Italy Lund Univ, Fac Law, Lund, Sweden Univ Gothenburg, Dept Microbiol & Immunol, Gothenburg, Sweden NARO, Kachwekano Zardi, Entebbe, Uganda Natl Yunlin Univ Sci & Technol, Bachelor Program Interdisciplinary Studies, Touliu, Yunlin, Taiwan Aarhus Univ, Dept Biomed, Danish Res Inst Translat Neurosci DANDRITE, Aarhus, Denmark Eduardo Mondlane Univ, Math & Comp Sci, Maputo, Mozambique Univ Bern, Dept Old Age Psychiat & Psychotherapy, Bern, Switzerland RAS, Inst Cytol, Lab Cytol Unicellular Organisms, St Petersburg, Russia Beijing Inst Technol, Sch Chem & Chem Engn, Beijing, Peoples R China Univ Queensland, Queensland Alliance Agr & Food Innovat, Brisbane, Qld, Australia Fraunhofer Inst Toxicol & Expt Med ITEM, Inhalat Toxicol, Hannover, Germany Univ Hong Kong, Publ Hlth, Hong Kong, Peoples R China Univ Hlth Network, Anesthesia & Pain Med, Toronto, ON, Canada Univ Toronto, Toronto, ON, Canada Univ Bath, Dept Hlth, Bath, Avon, England Univ Copenhagen, Computat & RNA Biol, Copenhagen, Denmark Fisheries & Oceans Canada, Bedford Inst Oceanog, Dartmouth, NS, Canada Goethe Univ, CEF MC, BMLS, Phys Biol, Frankfurt, Germany Albert Einstein Coll Med, Anat & Struct Biol, New York, NY USA Queensland Govt, Dept Environm & Sci, Brisbane, Qld, Australia Uppsala Univ, Vasc Surg Sect, Dept Surg Sci, Uppsala, Sweden Childrens Canc Hosp, Res, Cairo, Egypt Leibniz Inst Nat Prod Res & Infect Biol, Bio Pilot Plant, Jena, Germany Duy Tan Univ, Inst Res & Dev, Da Nang, Vietnam Univ Helsinki, Helsinki Inst Life Sci HiLIFE, Helsinki, Finland Univ Queensland, Australian Inst Bioengn & Nanotechnol, Brisbane, Qld, Australia George Inst Global Hlth, Sydney, NSW, Australia Griffith Univ, Griffith Inst Drug Discovery, Brisbane, Qld, Australia Dezhou Univ, Coll Phys & Elect Informat, Shandong Prov Key Lab Biophys, Dezhou, Peoples R China Henan Agr Univ, Coll Life Sci, Zhengzhou, Henan, Peoples R China Univ Tokyo, Publ Hlth, Tokyo, Japan Sun Yat Sen Univ, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China Univ Illinois, Dept Med, Chicago, IL USA Beijing Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, Beijing, Peoples R China Minist Hlth, Key Lab Neonatal Dis, Shanghai, Peoples R China Covenant Univ, Dept Phys, Ota, Nigeria Prince Sattam Bin Abdulaziz Univ, Dept Phys Therapy & Hlth Rehabil, Al Kharj, Saudi Arabia Lund Univ, Cognit Sci, Malmo, Sweden Natl Open Univ Nigeria, Dept Publ & Environm Hlth, Abuja, Nigeria Peking Univ, Sch Publ Hlth, Dept Lab Sci & Technol, Beijing, Peoples R China Univ Sydney, Sch Publ Hlth, Menzies Ctr Hlth Policy, Sydney, NSW, Australia Univ Auckland, Dept Elect & Comp Engn, Auckland, New Zealand Beijing Univ Chinese Med, Res Ctr TCM Informat Engn, Beijing, Peoples R China Osped Niguarda Ca Granda, Cardiac Surg, Milan, Italy Univ Vet Med, Clin Horses, Hannover, Germany Harbin Med Univ, Lab Med Genet, Harbin, Heilongjiang, Peoples R China Univ Saskatchewan, Dept Psychol, Saskatoon, SK, Canada Univ Coimbra, Ctr Studies Geog & Spatial Planning CEGOT, Coimbra, Portugal Univ Groningen, Univ Med Ctr Groningen, Epidemiol, Groningen, Netherlands South Cent High Specialty Hosp, Dept Neurol & Neurosurg, Pemex, Mexico Shandong Agr Univ, Coll Informat Sci & Engn, Tai An, Shandong, Peoples R China Curtin Univ, Natl Drug Res Inst, Perth, WA, Australia Wageningen Bioveterinary Res, Bacteriol & Epidemiol, Lelystad, Netherlands Guangdong Second Prov Gen Hosp, Dept Rheumatol & Immunol, Guangzhou, Guangdong, Peoples R China Erasmus MC, Biomed Rngineering, Rotterdam, Netherlands Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Hiroshima, Japan Univ Iceland, Sch Hlth Sci, Reykjavik, Iceland Ohio State Univ, Mat Sci & Engn, Columbus, OH 43210 USA Kathmandu Univ, Sch Med Sci, Dept Physiotherapy, Dhulikhel, Nepal Univ Queensland, Sch Biomed Sci, Brisbane, Qld, Australia Fraunhofer MEVIS, Image Guided Therapies, Bremen, Germany Natl Univ Hlth Syst, Haematol Oncol, Singapore, Singapore Sun Yat Sen Univ, Canc Ctr, Breast Oncol, Guangzhou, Guangdong, Peoples R China Med Coll Wisconsin, Pharmacol & Toxicol, Wauwatosa, WI USA Queensland Univ Technol, Sci & Engn Fac, Sch Chem Phys & Mech Engn, Brisbane, Qld, Australia Univ Turin, Dept Mol Biotechnol & Hlth Sci, Turin, Italy Univ Tehran Med Sci, Sch Rehabil, Physiotherapy Dept, Tehran, Iran Univ Helsinki, Dept Forest Sci, Helsinki, Finland Univ Messina, Human Pathol, Messina, Italy AO Papardo Hosp Messina, Messina, Italy Univ Ibadan, Coll Med, Inst Child Hlth, Ibadan, Nigeria King Faisal Univ, Coll Med, Fac Ophthalmol, Al Hasa, Saudi Arabia Univ Stirling, Inst Social Mkt, Stirling, Scotland Saveh Univ Med Sci, Social Determinants Hlth Res Ctr, Saveh, Iran Gakujutsu Shien Co Ltd, Tokyo, Japan Chinese Acad Sci, Inst Geochem, Guiyang, Guizhou, Peoples R China Univ Plymouth, Med Sch, Plymouth, Devon, England CHU Toulouse, Immunol, Toulouse, France Azorean Biodivers Grp, Ctr Ecol Evolut & Environm Changes, Azores, Portugal Univ Acores, Azores, Portugal RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan Peking Univ, Sch Publ Hlth, Dept Global Hlth, Beijing, Peoples R China Chang Gung Univ, Chang Gung Mem Hosp, Dept Neurol, Linkou Med Ctr, Taoyuan, Taiwan Chang Gung Univ, Coll Med, Taoyuan, Taiwan Univ Malawi, Coll Med, Biomed Sci Dept, Blantyre, Malawi Univ Malawi, Coll Med, Pharm Dept, Blantyre, Malawi Bioself Commun, Biocurat, Marseille, France Peking Univ, Hosp 3, Dept Neurol, Beijing, Peoples R China Ahmadu Bello Univ, Fac Basic Clin Sci, Coll Hlth Sci, Dept Pathol, Zaria, Nigeria Dalhousie Univ, Dept Anesthesia Pain Management & Perioperat Med, Halifax, NS, Canada VisMederi Srl, Siena, Italy UCL, Canc Res UK, London, England UCL, UCL Canc Trials Ctr, London, England Univ Ottawa, Family Med, Ottawa, ON, Canada China Agr Univ, Coll Engn, Beijing, Peoples R China Leiden Univ, Leiden Acad Ctr Drug Res, Div Drug Discovery & Safety, Leiden, Netherlands Sun Yat Sen Univ, Affiliated Hosp 1, Dept Intervent Radiol, Guangzhou, Guangdong, Peoples R China Amer Univ Beirut, Med Ctr, Infect Dis, Beirut, Lebanon Sheffield Hallam Univ, Dept Social Work Social Care & Community Studies, Sheffield, S Yorkshire, England Mechnikov Res Inst Vaccines & Sera, Viral Hepatitis, Moscow, Russia Univ Ottawa, Pediat, Ottawa, ON, Canada Vreden Russian Res Inst Traumatol & Orthopaed, Dept Wound Infect Treatment & Prevent, St Petersburg, Russia Hangzhou Ctr Dis Control & Prevent, Dept TB Control & Prevent, Hangzhou, Zhejiang, Peoples R China Kaohsiung Med Univ, Dept Biotechnol, Kaohsiung, Taiwan Zoetis, Diagnost, Kalamazoo, MI USA Aintree Univ Hosp NHS Fdn Trust, Head & Neck Oncol Res, Liverpool, Merseyside, England Wrightington Hosp, Trauma & Orthopaed, Manchester, Lancs, England Loyola Univ, Med Ctr, Dept Psychiat, 2160 S 1st Ave, Maywood, IL 60153 USA Atkins Vet Serv, Microbiol, Calgary, AB, Canada Univ Porto, FADEUP, CIAFEL, Porto, Portugal Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore Kangwon Natl Univ, Coll Biotechnol & Biosci, Dept Food Sci & Biotechnol, Chunchon, South Korea Kakatiya Med Coll, Internal Med, Warangal, Telangana, India Univ Antioquia, Vet Med Sch, CIBAV Res Grp, Medellin, Colombia IISER, Dept Phys, Soft & Act Matter Grp, Tirupati 517507, Andhra Pradesh, India Univ Rosario, Sch Med & Hlth, Ctr Studies Phys Activ Measurements, Bogota, Colombia Univ Hosp Essen, Cardiol & Vasc Med, Essen, Germany Univ Hosp Basel, Endocrinol, Basel, Switzerland Univ Tubingen, Inst Med Genet & Appl Genom, Tubingen, Germany Univ Hosp Munster, Div Gen Internal Med Nephrol & Rheumatolog, Dept Med D, Munster, Germany Univ Kentucky, Dept Nephrol, Lexington, KY USA Univ Freiburg, Dept Anaesthesiol & Crit Care, Med Ctr, Freiburg, Germany Univ Calif Irvine, Dept Med, Orange, CA 92668 USA Univ Hosp Leuven, Dept Urol, Leuven, Belgium Chinese Acad Sci, Coll Life Sci, Beijing, Peoples R China Univ Florida, Orthopaed & Rehabil, Gainesville, FL USA Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Mol Oncol & Epigenet, Chongqing, Peoples R China Tsinghua Univ, Dept Chem Engn, Beijing, Peoples R China Yonsei Univ, Coll Med, Dept Pharmacol, Seoul, South Korea Childrens Hosp Kings Daughters, Eastern Virginia Med Sch, Dept Pediat, Norfolk, VA USA China Three Gorges Univ, Coll Sci, Dept Math, Yichang, Peoples R China Xiangtan Univ, Coll Informat Engn, Xiangtan, Hunan, Peoples R China Univ Hlth Network, Mood Disorders & Psychopharmacol, Toronto, ON, Canada Sao Paulo State Univ UNESP, Dept Anim Sci, Sao Paulo, Brazil Sao Paulo State Univ, Vet Clin, Sao Paulo, Brazil
Published: 2019

9. A quantitative transcriptome reference map of the normal human brain

Author: Maria Caracausi, Lorenza Vitale, Pierluigi Strippoli, Samantha Bruno, Allison Piovesan, Maria Chiara Pelleri, Caracausi M, Vitale L, Pelleri MC, Piovesan A, Bruno S, and Strippoli P
Subjects: Adult, Male, Databases, Factual, In silico, Biology, Transcriptome, Cellular and Molecular Neuroscience, Fetus, Sex Factors, Gene expression, Genetics, medicine, Humans, Microarray databases, TRANSCRIPTOME, Gene, Genetics (clinical), GENE EXPRESSION PROFILE, Gene Expression Profiling, Brain, Human brain, META-ANALYSIS, HUMAN BRAIN, Human genetics, Gene expression profiling, medicine.anatomical_structure, Female
Abstract: We performed an innovative systematic meta-analysis of 60 gene expression profiles of whole normal human brain, to provide a quantitative transcriptome reference map of it, i.e. a reference typical value of expression for each of the 39,250 known, mapped and 26,026 uncharacterized (unmapped) transcripts. To this aim, we used the software named Transcriptome Mapper (TRAM), which is able to generate transcriptome maps based on gene expression data from multiple sources. We also analyzed differential expression by comparing the brain transcriptome with those derived from human foetal brain gene expression, from a pool of human tissues (except the brain) and from the two normal human brain regions cerebellum and cerebral cortex, which are two of the main regions severely affected when cognitive impairment occurs, as happens in the case of trisomy 21. Data were downloaded from microarray databases, processed and analyzed using TRAM software and validated in vitro by assaying gene expression through several magnitude orders by 'real-time' reverse transcription polymerase chain reaction (RT-PCR). The excellent agreement between in silico and experimental data suggested that our transcriptome maps may be a useful quantitative reference benchmark for gene expression studies related to the human brain. Furthermore, our analysis yielded biological insights about those genes which have an intrinsic over-/under-expression in the brain, in addition offering a basis for the regional analysis of gene expression. This could be useful for the study of chromosomal alterations associated to cognitive impairment, such as trisomy 21, the most common genetic cause of intellectual disability.
Published: 2014

10. Genome-scale analysis of human mRNA 5′ coding sequences based on expressed sequence tag (EST) database

Author: Lorenza Vitale, Eva Bianconi, Silvia Canaider, Federica Facchin, Maria Chiara Pelleri, Allison Piovesan, Pierluigi Strippoli, Raffaella Casadei, Flavia Frabetti, Piovesan A, Casadei R, Vitale L, Facchin F, Pelleri MC, Canaider S, Bianconi E, Frabetti F, Strippoli P., Casadei R., Piovesan A., Vitale L., Facchin F., Pelleri M.C., Canaider S., Bianconi E., and Frabetti F.
Subjects: DNA, Complementary, Five prime untranslated region, Molecular Sequence Data, Codon, Initiator, Biology, Open Reading Frames, Start codon, Databases, Genetic, Genetics, Humans, HUMAN GENOME, Coding region, MRNA 5&#8242, CODING SEQUENCE, Amino Acid Sequence, RNA, Messenger, Cloning, Molecular, Genetic Association Studies, Expressed Sequence Tags, Expressed sequence tag, Genome, Human, 5&#8242, UNTRANSLATED REGION (5&#8242, UTR), mRNA 5′ coding sequence, Computational Biology, Shine-Dalgarno sequence, 5′ Untranslated region (5′ UTR), Sequence Analysis, DNA, EXPRESSED SEQUENCE TAG (EST), Stop codon, TRANSLATION START CODON, Open reading frame, Genetic Loci, Human genome, 5' Untranslated Regions, Sequence Alignment
Abstract: The term "5´ end mRNA artifact" refers to the incorrect assignment of the first AUG codon in an mRNA, due to the incomplete determination of its 5´ end sequence (Casadei et al., 2003). Since the '70s, the amino acid sequence of gene products has been routinely deduced from the nucleotide sequence of the relative cloned cDNA (DNA complementary to mRNA), according to rules for recognition of the start codon (first-AUG rule, optimal sequence context) and the genetic code (Kozak, 2002). All standard methods for the cloning of cDNA are affected by a potential inability to effectively clone the 5´ region of mRNA. This is due to the reverse transcriptase failure to extend first-strand cDNA along the full length of the mRNA template toward its 5´ end (Sambrook, 2001). The identification of a more complete mRNA 5´ end could reveal an additional upstream AUG – in-frame with the previously determined one – thus extending the predicted amino terminus sequence of the product and avoiding subsequent relevant errors in the experimental study of the relative cDNA (Casadei et al., 2003). The continuous incorporation of information derived from individual and large-scale cDNA sequencing projects, including those specifically designed to characterize mRNA 5´ end (Carninci et al., 1996; Suzuki et al., 2000; Porcel et al., 2004), in the last few years led to continuous improvement of completeness of mRNA reference sequences (e.g., RefSeq), and also to the corresponding protein coding sequences. However, genome browsers do not appear to systematically extract useful information from the ever-increasing vast quantity of EST (expressed sequence tag) data. To date, EST data remain invaluable due to significantly longer continuous RNA sequences they may provide in comparison with the very short fragments typically deposited in current high-throughput nucleotide sequencing databases. We previously used individual EST-based gene model refinement by classic in silico sequence analysis to revise the mRNA sequence of 109 human chromosome 21 protein-coding genes (Casadei et al., 2003). The success of this approach encouraged us to develop a piece of software ("5'_ORF_Extender" software) in order to automate the steps that were previously performed manually, applying it to the Danio rerio (zebrafish) genome (Frabetti et al., 2007). In the present work, we present a modified strategy able to analyze the much more numerous human sequences. Firstly, we fully revised the software algorithm by using pre-computed coordinates of the UCSC-downloaded RefSeqs and ESTs genome alignment data and specific UCSC-downloaded EST sequence entries. Furthermore, we adopted an original quality filter which was able to test if each single EST candidate with sequence information of possible use for extending a known mRNA, was attributed to the same locus of that mRNA by an updated, complete and embedded version of UniGene. Lastly, we automated data summarization for an analyzed genome. Following these improvements, parsing more than 7 million BLAT alignment, 5'_ORF_Extender 2.0 recognized a total of 477 loci, out of the 18,665 human loci represented in the mRNA reference set, as bona fide candidates for extension. Proof-of-concept confirmation was obtained by in vitro cloning and sequencing for GNB2L1 (guanine nucleotide binding protein (G protein), beta polypeptide 2-like 1), QARS (glutaminyl-tRNA synthetase) and TDP2 (tyrosyl-DNA phosphodiesterase 2) cDNAs, and the consequences for the functional studies of these loci are discussed. In addition, we generated a list of 20,775 human mRNAs in which the presence of an in-frame stop codon upstream of the known start codon indicates completeness of the coding sequence at 5´ in the current form. Bibliografia: R. Casadei et al., mRNA 5’ region sequence incompleteness: a potential source of systematic errors in translation initiation codon assignment in human mRNAs, Gene 321 (2003) 185–193. M. Kozak, Pushing the limits of the scanning mechanism for initiation of translation, Gene 99 (2002) 1–34. P. Carninci et al., High-efficiency fulllength cDNA cloning by biotinylated CAP trapper, Genomics 37 (1996) 327–336. F. Frabetti et al., Systematic analysis of mRNA 5’ coding sequence incompleteness in Danio rerio: an automated EST-based approach, Biol. Direct 2 (2007) 34.
Published: 2012

11. The functional roles of S-adenosyl-methionine and S-adenosyl-homocysteine and their involvement in trisomy 21.

Author: Caracausi M, Ramacieri G, Catapano F, Cicilloni M, Lajin B, Pelleri MC, Piovesan A, Vitale L, Locatelli C, Pirazzoli GL, Strippoli P, Antonaros F, and Vione B
Subjects: Humans, Epigenesis, Genetic, Cell Proliferation, Down Syndrome metabolism, Down Syndrome genetics, Down Syndrome blood, S-Adenosylmethionine metabolism, S-Adenosylhomocysteine metabolism, S-Adenosylhomocysteine blood
Abstract: The one-carbon metabolism pathway is involved in critical human cellular functions such as cell proliferation, mitochondrial respiration, and epigenetic regulation. In the homocysteine-methionine cycle S-adenosyl-methionine (SAM) and S-adenosyl-homocysteine (SAH) are synthetized, and their levels are finely regulated to ensure proper functioning of key enzymes which control cellular growth and differentiation. Here we review the main biological mechanisms involving SAM and SAH and the known related human diseases. It was recently demonstrated that SAM and SAH levels are altered in plasma of subjects with trisomy 21 (T21) but how this metabolic dysregulation influences the clinical manifestation of T21 phenotype has not been previously described. This review aims at providing an overview of the biological mechanisms which are altered in response to changes in the levels of SAM and SAH observed in DS., (© 2024 The Authors. BioFactors published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.)
Published: 2024
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12. Corrigendum: One-carbon pathway metabolites are altered in the plasma of subjects with Down syndrome: relation to chromosomal dosage.

Author: Vione B, Ramacieri G, Zavaroni G, Piano A, La Rocca G, Caracausi M, Vitale L, Piovesan A, Gori C, Pirazzoli GL, Strippoli P, Cocchi G, Corvaglia L, Locatelli C, Pelleri MC, and Antonaros F
Abstract: [This corrects the article DOI: 10.3389/fmed.2022.1006891.]., (Copyright © 2024 Vione, Ramacieri, Zavaroni, Piano, La Rocca, Caracausi, Vitale, Piovesan, Gori, Pirazzoli, Strippoli, Cocchi, Corvaglia, Locatelli, Pelleri and Antonaros.)
Published: 2024
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13. Zinc metabolism and its role in immunity status in subjects with trisomy 21: chromosomal dosage effect.

Author: Ramacieri G, Locatelli C, Semprini M, Pelleri MC, Caracausi M, Piovesan A, Cicilloni M, Vigna M, Vitale L, Sperti G, Corvaglia LT, Pirazzoli GL, Strippoli P, Catapano F, Vione B, and Antonaros F
Subjects: Humans, Female, Male, Child, Preschool, Child, Superoxide Dismutase-1 genetics, Adult, Adolescent, Transcriptome, Young Adult, Infant, Gene Expression Profiling, Immunity genetics, Middle Aged, Down Syndrome immunology, Down Syndrome genetics, Zinc blood
Abstract: Introduction: Trisomy 21 (T21), which causes Down syndrome (DS), is the most common chromosomal aneuploidy in humankind and includes different clinical comorbidities, among which the alteration of the immune system has a heavy impact on patient's lives. A molecule with an important role in immune response is zinc and it is known that its concentration is significantly lower in children with T21. Different hypotheses were made about this metabolic alteration and one of the reasons might be the overexpression of superoxide dismutase 1 ( SOD1 ) gene, as zinc is part of the SOD1 active enzymatic center., Methods: The aim of our work is to explore if there is a linear correlation between zinc level and immune cell levels measured in a total of 217 blood samples from subjects with T21. Furthermore, transcriptome map analyses were performed using Transcriptome Mapper (TRAM) software to investigate whether a difference in gene expression is detectable between subjects with T21 and euploid control group in tissues and cells involved in the immune response such as lymphoblastoid cells, thymus and white blood cells., Results: Our results have confirmed the literature data stating that the blood zinc level in subjects with T21 is lower compared to the general population; in addition, we report that the T21/control zinc concentration ratio is 2:3, consistent with a chromosomal dosage effect due to the presence of three copies of chromosome 21. The transcriptome map analyses showed an alteration of some gene's expression which might explain low levels of zinc in the blood., Discussion: Our data suggest that zinc level is not associated with the levels of immunity cells or proteins analyzed themselves and rather the main role of this ion might be played in altering immune cell function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ramacieri, Locatelli, Semprini, Pelleri, Caracausi, Piovesan, Cicilloni, Vigna, Vitale, Sperti, Corvaglia, Pirazzoli, Strippoli, Catapano, Vione and Antonaros.)
Published: 2024
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14. Machine learning based analysis for intellectual disability in Down syndrome.

Author: Baldo F, Piovesan A, Rakvin M, Ramacieri G, Locatelli C, Lanfranchi S, Onnivello S, Pulina F, Caracausi M, Antonaros F, Lombardi M, and Pelleri MC
Abstract: Down syndrome (DS) or trisomy 21 is the most common genetic cause of intellectual disability (ID), but a pathogenic mechanism has not been identified yet. Studying a complex and not monogenic condition such as DS, a clear correlation between cause and effect might be difficult to find through classical analysis methods, thus different approaches need to be used. The increased availability of big data has made the use of artificial intelligence (AI) and in particular machine learning (ML) in the medical field possible. The purpose of this work is the application of ML techniques to provide an analysis of clinical records obtained from subjects with DS and study their association with ID. We have applied two tree-based ML models (random forest and gradient boosting machine) to the research question: how to identify key features likely associated with ID in DS. We analyzed 109 features (or variables) in 106 DS subjects. The outcome of the analysis was the age equivalent (AE) score as indicator of intellectual functioning, impaired in ID. We applied several methods to configure the models: feature selection through Boruta framework to minimize random correlation; data augmentation to overcome the issue of a small dataset; age effect mitigation to take into account the chronological age of the subjects. The results show that ML algorithms can be applied with good accuracy to identify variables likely involved in cognitive impairment in DS. In particular, we show how random forest and gradient boosting machine produce results with low error (MSE <0.12) and an acceptable R 2 (0.70 and 0.93). Interestingly, the ranking of the variables point to several features of interest related to hearing, gastrointestinal alterations, thyroid state, immune system and vitamin B12 that can be considered with particular attention for improving care pathways for people with DS. In conclusion, ML-based model may assist researchers in identifying key features likely correlated with ID in DS, and ultimately, may improve research efforts focused on the identification of possible therapeutic targets and new care pathways. We believe this study can be the basis for further testing/validating of our algorithms with multiple and larger datasets., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)
Published: 2023
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15. Partial trisomy 21 with or without highly restricted Down syndrome critical region (HR-DSCR): report of two new cases and reanalysis of the genotype-phenotype association.

Author: Pelleri MC, Locatelli C, Mattina T, Bonaglia MC, Piazza F, Magini P, Antonaros F, Ramacieri G, Vione B, Vitale L, Seri M, Strippoli P, Cocchi G, Piovesan A, and Caracausi M
Subjects: Child, Humans, Trisomy, Genetic Association Studies, Chromosomes, Human, Pair 21 genetics, Phenotype, Down Syndrome genetics, Down Syndrome pathology, Intellectual Disability genetics
Abstract: Background: Down syndrome (DS) is caused by the presence of an extra copy of full or partial human chromosome 21 (Hsa21). Partial (segmental) trisomy 21 (PT21) is the duplication of only a delimited region of Hsa21 and can be associated or not to DS: the study of PT21 cases is an invaluable model for addressing genotype-phenotype correlation in DS. Previous works reported systematic reanalyses of 132 subjects with PT21 and allowed the identification of a 34-kb highly restricted DS critical region (HR-DSCR) as the minimal region whose duplication is shared by all PT21 subjects diagnosed with DS., Methods: We report clinical data and cytogenetic analysis of two children with PT21, one with DS and the other without DS. Moreover, we performed a systematic bibliographic search for any new PT21 report., Results: Clinical and cytogenetic analyses of the two PT21 children have been reported: in Case 1 the duplication involves the whole long arm of Hsa21, except for the last 2.7 Mb, which are deleted as a consequence of an isodicentric 21: the HR-DSCR is within the duplicated regions and the child is diagnosed with DS. In Case 2 the duplication involves 7.1 Mb of distal 21q22, with a deletion of 2.1 Mb of proximal 20p, as a consequence of an unbalanced translocation: the HR-DSCR is not duplicated and the child presents with psychomotor development delay but no clinical signs of DS. Furthermore, two PT21 reports recently published (named Case 3 and 4) have been discussed: Case 3 has DS diagnosis, nearly full trisomy for Hsa21 and a monosomy for the 21q22.3 region. Case 4 is a baby without DS and a 0.56-Mb duplication of 21q22.3. Genotype-phenotype correlation confirmed the presence of three copies of the HR-DSCR in all DS subjects and two copies in all non-DS individuals., Conclusions: The results presented here are fully consistent with the hypothesis that the HR-DSCR is critically associated with DS diagnosis. No exception to this pathogenetic model was found. Further studies are needed to detect genetic determinants likely located in the HR-DSCR and possibly responsible for core DS features, in particular intellectual disability., (© 2022. The Author(s).)
Published: 2022
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16. One-carbon pathway metabolites are altered in the plasma of subjects with Down syndrome: Relation to chromosomal dosage.

Author: Vione B, Ramacieri G, Zavaroni G, Piano A, La Rocca G, Caracausi M, Vitale L, Piovesan A, Gori C, Pirazzoli GL, Strippoli P, Cocchi G, Corvaglia L, Locatelli C, Pelleri MC, and Antonaros F
Abstract: Introduction: Down syndrome (DS) is the most common chromosomal disorder and it is caused by trisomy of chromosome 21 (Hsa21). Subjects with DS show a large heterogeneity of phenotypes and the most constant clinical features present are typical facies and intellectual disability (ID). Several studies demonstrated that trisomy 21 causes an alteration in the metabolic profile, involving among all the one-carbon cycle., Methods: We performed enzyme-linked immunosorbent assays (ELISAs) to identify the concentration of 5 different intermediates of the one-carbon cycle in plasma samples obtained from a total of 164 subjects with DS compared to 54 euploid subjects. We investigated: tetrahydrofolate (THF; DS n = 108, control n = 41), 5-methyltetrahydrofolate (5-methyl-THF; DS n = 140, control n = 34), 5-formyltetrahydrofolate (5-formyl-THF; DS n = 80, control n = 21), S-adenosyl-homocysteine (SAH; DS n = 94, control n = 20) and S-adenosyl-methionine (SAM; DS n = 24, control n = 15)., Results: Results highlight specific alterations of THF with a median concentration ratio DS/control of 2:3, a decrease of a necessary molecule perfectly consistent with a chromosomal dosage effect. Moreover, SAM and SAH show a ratio DS/control of 1.82:1 and 3.6:1, respectively., Discussion: The relevance of these results for the biology of intelligence and its impairment in trisomy 21 is discussed, leading to the final proposal of 5-methyl-THF as the best candidate for a clinical trial aimed at restoring the dysregulation of one-carbon cycle in trisomy 21, possibly improving cognitive skills of subjects with DS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Vione, Ramacieri, Zavaroni, Piano, La Rocca, Caracausi, Vitale, Piovesan, Gori, Pirazzoli, Strippoli, Cocchi, Corvaglia, Locatelli, Pelleri and Antonaros.)
Published: 2022
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17. A reassessment of Jackson's checklist and identification of two Down syndrome sub-phenotypes.

Author: Locatelli C, Onnivello S, Gori C, Ramacieri G, Pulina F, Marcolin C, Vianello R, Vione B, Caracausi M, Pelleri MC, Vitale L, Pirazzoli GL, Cocchi G, Corvaglia L, Strippoli P, Antonaros F, Piovesan A, and Lanfranchi S
Subjects: Checklist, Down Syndrome physiopathology, Genetics, Behavioral methods, Humans, Intellectual Disability diagnosis, Intellectual Disability genetics, Neurology methods, Phenotype, Down Syndrome diagnosis
Abstract: Down syndrome (DS) is characterised by several clinical features including intellectual disability (ID) and craniofacial dysmorphisms. In 1976, Jackson and coll. identified a checklist of signs for clinical diagnosis of DS; the utility of these checklists in improving the accuracy of clinical diagnosis has been recently reaffirmed, but they have rarely been revised. The purpose of this work is to reassess the characteristic phenotypic signs and their frequencies in 233 DS subjects, following Jackson's checklist. 63.77% of the subjects showed more than 12 signs while none showed less than 5, confirming the effectiveness of Jackson's checklist for the clinical diagnosis of DS. An association between three phenotypic signs emerged, allowing us to distinguish two sub-phenotypes: Brachycephaly, short and broad Hands, short Neck (BHN), which is more frequent, and "non-BHN". The strong association of these signs might be interpreted in the context of the growth defects observed in DS children suggesting decreased cell proliferation. Lastly, cognitive assessments were investigated for 114 subjects. The lack of association between the presence of a physical sign or the number of signs present in a subject and cognitive skills disproves the stereotype that physical characteristics are predictive of degree of ID., (© 2022. The Author(s).)
Published: 2022
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18. Structural Characterization of the Highly Restricted Down Syndrome Critical Region on 21q22.13: New KCNJ6 and DSCR4 Transcript Isoforms.

Author: Antonaros F, Pitocco M, Abete D, Vione B, Piovesan A, Vitale L, Strippoli P, Caracausi M, and Pelleri MC
Abstract: Down syndrome (DS) is caused by trisomy of chromosome 21 and it is the most common genetic cause of intellectual disability (ID) in humans. Subjects with DS show a typical phenotype marked by facial dysmorphisms and ID. Partial trisomy 21 (PT21) is a rare genotype characterized by the duplication of a delimited chromosome 21 (Hsa21) portion and it may or may not be associated with DS diagnosis. The highly restricted Down syndrome critical region (HR-DSCR) is a region of Hsa21 present in three copies in all individuals with PT21 and a diagnosis of DS. This region, located on distal 21q22.13, is 34 kbp long and does not include characterized genes. The HR-DSCR is annotated as an intergenic region between KCNJ6-201 transcript encoding for potassium inwardly rectifying channel subfamily J member 6 and DSCR4-201 transcript encoding Down syndrome critical region 4. Two transcripts recently identified by massive RNA-sequencing (RNA-Seq) and automatically annotated on Ensembl database reveal that the HR-DSCR seems to be partially crossed by KCNJ6-202 and DSCR4-202 isoforms. KCNJ6-202 shares the coding sequence with KCNJ6-201 which is involved in many physiological processes, including heart rate in cardiac cells and circuit activity in neuronal cells. DSCR4-202 transcript has the first two exons in common with DSCR4-201 , the only experimentally verified gene uniquely present in Hominidae . In this study, we performed in silico and in vitro analyses of the HR-DSCR. Bioinformatic data, obtained using Sequence Read Archive (SRA) and SRA-BLAST software, were confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Sanger sequencing on a panel of human tissues. Our data demonstrate that the HR-DSCR cannot be defined as an intergenic region. Further studies are needed to investigate the functional role of the new transcripts, likely involved in DS phenotypes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Antonaros, Pitocco, Abete, Vione, Piovesan, Vitale, Strippoli, Caracausi and Pelleri.)
Published: 2021
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19. Is the Age of Developmental Milestones a Predictor for Future Development in Down Syndrome?

Author: Locatelli C, Onnivello S, Antonaros F, Feliciello A, Filoni S, Rossi S, Pulina F, Marcolin C, Vianello R, Toffalini E, Ramacieri G, Martelli A, Procaccini G, Sperti G, Caracausi M, Pelleri MC, Vitale L, Pirazzoli GL, Strippoli P, Cocchi G, Piovesan A, and Lanfranchi S
Abstract: Down Syndrome (DS) is the most common genetic alteration responsible for intellectual disability, which refers to deficits in both intellectual and adaptive functioning. According to this, individuals with Down Syndrome (DS) reach developmental milestones (e.g., sitting, walking, and babbling) in the same order as their typically developing peers, but later in life. Since developmental milestones are the first blocks on which development builds, the aims of the current study are to: (i) expand the knowledge of developmental milestone acquisition; and (ii) explore the relationship between developmental milestone acquisition and later development. For this purpose 105 children/adolescents with DS were involved in this study, divided in two groups, Preschoolers ( n = 39) and School-age participants ( n = 66). Information on the age of acquisition of Sitting, Walking, Babbling, and Sphincter Control was collected, together with cognitive, motor, and adaptive functioning. Sitting predicted later motor development, but, with age, it became less important in predicting motor development in everyday life. Babbling predicted later language development in older children. Finally, Sphincter Control emerged as the strongest predictor of motor, cognitive, language, and adaptive skills, with its role being more evident with increasing age. Our data suggest that the age of reaching the milestones considered in the study has an influence on successive development, a role that can be due to common neural substrates, the environment, and the developmental cascade effect.
Published: 2021
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20. The transcriptome profile of human trisomy 21 blood cells.

Author: Antonaros F, Zenatelli R, Guerri G, Bertelli M, Locatelli C, Vione B, Catapano F, Gori A, Vitale L, Pelleri MC, Ramacieri G, Cocchi G, Strippoli P, Caracausi M, and Piovesan A
Subjects: Blood Cells metabolism, Blood Cells pathology, Chromosomes, Human, Pair 21 genetics, Down Syndrome epidemiology, Down Syndrome pathology, Energy Metabolism genetics, Gene Expression Regulation genetics, Genome, Human genetics, Humans, Intellectual Disability epidemiology, Intellectual Disability genetics, Intellectual Disability pathology, Mitochondria genetics, Mitochondria metabolism, RNA-Seq, Software, Transcriptome genetics, Carbon-Nitrogen Ligases genetics, Down Syndrome genetics, Myxovirus Resistance Proteins genetics, Phosphoribosylglycinamide Formyltransferase genetics, Reduced Folate Carrier Protein genetics
Abstract: Background: Trisomy 21 (T21) is a genetic alteration characterised by the presence of an extra full or partial human chromosome 21 (Hsa21) leading to Down syndrome (DS), the most common form of intellectual disability (ID). It is broadly agreed that the presence of extra genetic material in T21 gives origin to an altered expression of genes located on Hsa21 leading to DS phenotype. The aim of this study was to analyse T21 and normal control blood cell gene expression profiles obtained by total RNA sequencing (RNA-Seq)., Results: The results were elaborated by the TRAM (Transcriptome Mapper) software which generated a differential transcriptome map between human T21 and normal control blood cells providing the gene expression ratios for 17,867 loci. The obtained gene expression profiles were validated through real-time reverse transcription polymerase chain reaction (RT-PCR) assay and compared with previously published data. A post-analysis through transcriptome mapping allowed the identification of the segmental (regional) variation of the expression level across the whole genome (segment-based analysis of expression). Interestingly, the most over-expressed genes encode for interferon-induced proteins, two of them (MX1 and MX2 genes) mapping on Hsa21 (21q22.3). The altered expression of genes involved in mitochondrial translation and energy production also emerged, followed by the altered expression of genes encoding for the folate cycle enzyme, GART, and the folate transporter, SLC19A1., Conclusions: The alteration of these pathways might be linked and involved in the manifestation of ID in DS.
Published: 2021
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21. One-carbon pathway and cognitive skills in children with Down syndrome.

Author: Antonaros F, Lanfranchi S, Locatelli C, Martelli A, Olivucci G, Cicchini E, Carosi Diatricch L, Mannini E, Vione B, Feliciello A, Ramacieri G, Onnivello S, Vianello R, Vitale L, Pelleri MC, Strippoli P, Cocchi G, Pulina F, Piovesan A, and Caracausi M
Subjects: Biomarkers, Child, Down Syndrome genetics, Fasting, Female, Homocysteine blood, Humans, Male, Methylenetetrahydrofolate Reductase (NADPH2) genetics, Methylenetetrahydrofolate Reductase (NADPH2) metabolism, Carbon metabolism, Cognition, Down Syndrome metabolism, Down Syndrome psychology, Energy Metabolism, Metabolic Networks and Pathways
Abstract: This work investigates the role of metabolite levels in the intellectual impairment of subjects with Down syndrome (DS). Homocysteine, folate, vitamin B12, uric acid (UA), creatinine levels and MTHFR C677T genotype were analyzed in 147 subjects with DS. For 77 subjects, metabolite levels were correlated with cognitive tests. Griffiths-III test was administered to 28 subjects (3.08-6.16 years) and WPPSI-III test was administered to 49 subjects (7.08-16.08 years). Significant correlations were found among some metabolite levels and between homocysteine levels and MTHFR C677T genotype. Moreover, homocysteine, UA and creatinine levels resulted increased with age. We did not find any correlation between metabolites and cognitive test score in the younger group. Homocysteine showed statistically significant correlation with WPPSI-III subtest scores when its level is ≥ 7.35 µmol/L, remaining correlated in higher thresholds only for non-verbal area scores. Vitamin B12 showed correlations with all WPPSI-III subtest scores when its level is < 442 pg/mL. The relevance of the present findings is the detection of a specific metabolite threshold related with a better or worse cognitive score, suggesting that vitamin B12 and homocysteine may have a role in cognitive development in children with DS.
Published: 2021
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22. Plasma metabolome and cognitive skills in Down syndrome.

Author: Antonaros F, Ghini V, Pulina F, Ramacieri G, Cicchini E, Mannini E, Martelli A, Feliciello A, Lanfranchi S, Onnivello S, Vianello R, Locatelli C, Cocchi G, Pelleri MC, Vitale L, Strippoli P, Luchinat C, Turano P, Piovesan A, and Caracausi M
Subjects: Adolescent, Adult, Case-Control Studies, Child, Child, Preschool, Down Syndrome genetics, Down Syndrome metabolism, Female, Humans, Intellectual Disability blood, Intellectual Disability genetics, Intellectual Disability metabolism, Intellectual Disability physiopathology, Magnetic Resonance Spectroscopy methods, Male, Metabolomics methods, Mitochondria metabolism, Multivariate Analysis, Trisomy genetics, Young Adult, Cognition physiology, Down Syndrome blood, Down Syndrome physiopathology, Metabolome physiology, Plasma metabolism
Abstract: Trisomy 21 (Down syndrome, DS) is the main human genetic cause of intellectual disability (ID). Lejeune hypothesized that DS could be considered a metabolic disease, and we found that subjects with DS have a specific plasma and urinary metabolomic profile. In this work we confirmed the alteration of mitochondrial metabolism in DS and also investigated if metabolite levels are related to cognitive aspects of DS. We analyzed the metabolomic profiles of plasma samples from 129 subjects with DS and 46 healthy control (CTRL) subjects by 1 H Nuclear Magnetic Resonance (NMR). Multivariate analysis of the NMR metabolomic profiles showed a clear discrimination (up to 94% accuracy) between the two groups. The univariate analysis revealed a significant alteration in 7 metabolites out of 28 assigned unambiguously. Correlations among the metabolite levels in DS and CTRL groups were separately investigated and statistically significant relationships appeared. On the contrary, statistically significant correlations among the NMR-detectable part of DS plasma metabolome and the different intelligence quotient ranges obtained by Griffiths-III or WPPSI-III tests were not found. Even if metabolic imbalance provides a clear discrimination between DS and CTRL groups, it appears that the investigated metabolomic profiles cannot be associated with the degree of ID.
Published: 2020
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23. Dysregulation of NIPBL leads to impaired RUNX1 expression and haematopoietic defects.

Author: Mazzola M, Pezzotta A, Fazio G, Rigamonti A, Bresciani E, Gaudenzi G, Pelleri MC, Saitta C, Ferrari L, Parma M, Fumagalli M, Biondi A, Cazzaniga G, Marozzi A, and Pistocchi A
Subjects: Adult, Aged, Animals, Bone Marrow Cells metabolism, Cell Cycle Proteins metabolism, Child, Cohort Studies, Core Binding Factor Alpha 2 Subunit metabolism, Down-Regulation genetics, Humans, Leukemia, Myeloid, Acute genetics, Megakaryocytes metabolism, Middle Aged, Tissue Donors, Zebrafish genetics, Zebrafish Proteins metabolism, Cell Cycle Proteins genetics, Core Binding Factor Alpha 2 Subunit genetics, Gene Expression Regulation, Leukemic, Hematopoiesis genetics, Zebrafish Proteins genetics
Abstract: The transcription factor RUNX1, a pivotal regulator of HSCs and haematopoiesis, is a frequent target of chromosomal translocations, point mutations or altered gene/protein dosage. These modifications lead or contribute to the development of myelodysplasia, leukaemia or platelet disorders. A better understanding of how regulatory elements contribute to fine-tune the RUNX1 expression in haematopoietic tissues could improve our knowledge of the mechanisms responsible for normal haematopoiesis and malignancy insurgence. The cohesin RAD21 was reported to be a regulator of RUNX1 expression in the human myeloid HL60 cell line and during primitive haematopoiesis in zebrafish. In our study, we demonstrate that another cohesin, NIPBL, exerts positive regulation of RUNX1 in three different contexts in which RUNX1 displays important functions: in megakaryocytes derived from healthy donors, in bone marrow samples obtained from adult patients with acute myeloid leukaemia and during zebrafish haematopoiesis. In this model, we demonstrate that alterations in the zebrafish orthologue nipblb reduce runx1 expression with consequent defects in its erythroid and myeloid targets such as gata1a and spi1b in an opposite way to rad21. Thus, also in the absence of RUNX1 translocation or mutations, additional factors such as defects in the expression of NIPBL might induce haematological diseases., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
Published: 2020
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24. Partial trisomy 21 map: Ten cases further supporting the highly restricted Down syndrome critical region (HR-DSCR) on human chromosome 21.

Author: Pelleri MC, Cicchini E, Petersen MB, Tranebjaerg L, Mattina T, Magini P, Antonaros F, Caracausi M, Vitale L, Locatelli C, Seri M, Strippoli P, Piovesan A, and Cocchi G
Subjects: Adolescent, Adult, Child, Child, Preschool, Comparative Genomic Hybridization, Computational Biology, Female, Genetic Association Studies, Humans, Infant, Male, Retrospective Studies, Chromosomes, Human, Pair 21, Down Syndrome genetics, Trisomy genetics
Abstract: Background: Down syndrome (DS) is characterized by the presence of an extra full or partial human chromosome 21 (Hsa21). An invaluable model to define genotype-phenotype correlations in DS is the study of the extremely rare cases of partial (segmental) trisomy 21 (PT21), the duplication of only a delimited region of Hsa21 associated or not to DS. A systematic retrospective reanalysis of 125 PT21 cases described up to 2015 allowed the creation of the most comprehensive PT21 map and the identification of a 34-kb highly restricted DS critical region (HR-DSCR) as the minimal region whose duplication is shared by all PT21 subjects diagnosed with DS. We reanalyzed at higher resolution three cases previously published and we accurately searched for any new PT21 reports in order to verify whether HR-DSCR limits could prospectively be confirmed and possibly refined., Methods: Hsa21 partial duplications of three PT21 subjects were refined by adding array-based comparative genomic hybridization data. Seven newly described PT21 cases fulfilling stringent cytogenetic and clinical criteria have been incorporated into the PT21 integrated map., Results: The PT21 map now integrates fine structure of Hsa21 sequence intervals of 132 subjects onto a common framework fully consistent with the presence of a duplicated HR-DSCR, on distal 21q22.13 sub-band, only in DS subjects and not in non-DS individuals. No documented exception to the HR-DSCR model was found., Conclusions: The findings presented here further support the association of the HR-DSCR with the diagnosis of DS, representing an unbiased validation of the original model. Further studies are needed to identify and characterize genetic determinants presumably located in the HR-DSCR and functionally associated to the critical manifestations of DS., (© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)
Published: 2019
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25. Reference quantitative transcriptome dataset for adult Caenorhabditis elegans .

Author: Piovesan A, Antonaros F, Strippoli P, Vitale L, Pelleri MC, and Caracausi M
Abstract: Caenorhabditis elegans is a nematode widely used in biology and genomics as a model organism. We provide an integrated, quantitative reference map for the transcriptome of whole, wild type Bristol N2 strain C. elegans worms. The map has been obtained by meta-analysis of 110 gene expression profiles available in Gene Expression Omnibus (GEO) repository and integrated using the computational biology tool Transcriptome Mapper (TRAM). Following probe assignment to the relative locus and intra- and inter-sample normalization (in particular using the scaled quantile method), a mean, consensus reference value is provided for 45,932 transcripts, along with standard deviation. Expression values are all mapped in the context of genomic coordinates. The map provides easy access to relationships among expression values of different genes in this standard condition, highlights genomic segments with relatively high over-/under-expression and may serve as a reference to test for gene expression variation for both individual genes and the whole transcriptome in specific biological conditions (e.g. mutated strains or differently grown worms).
Published: 2019
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26. Human protein-coding genes and gene feature statistics in 2019.

Author: Piovesan A, Antonaros F, Vitale L, Strippoli P, Pelleri MC, and Caracausi M
Subjects: Databases, Genetic, Exons, Gene Expression Regulation, Humans, Introns, Nuclear Proteins metabolism, Open Reading Frames, Computational Biology statistics & numerical data, Genome, Human, Nuclear Proteins genetics, Software, Transcriptome
Abstract: Objective: A well-known limit of genome browsers is that the large amount of genome and gene data is not organized in the form of a searchable database, hampering full management of numerical data and free calculations. Due to the continuous increase of data deposited in genomic repositories, their content revision and analysis is recommended. Using GeneBase, a software with a graphical interface able to import and elaborate National Center for Biotechnology Information (NCBI) Gene database entries, we provide tabulated spreadsheets updated to 2019 about human nuclear protein-coding gene data set ready to be used for any type of analysis about genes, transcripts and gene organization., Results: Comparison with previous reports reveals substantial change in the number of known nuclear protein-coding genes (now 19,116), the protein-coding non-redundant transcriptome space [now 59,281,518 base pair (bp), 10.1% increase], the number of exons (now 562,164, 36.2% increase) due to a relevant increase of the RNA isoforms recorded. Other parameters such as gene, exon or intron mean and extreme length appear to have reached a stability that is unlikely to be substantially modified by human genome data updates, at least regarding protein-coding genes. Finally, we confirm that there are no human introns shorter than 30 bp.
Published: 2019
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27. MTHFR C677T polymorphism analysis: A simple, effective restriction enzyme-based method improving previous protocols.

Author: Antonaros F, Olivucci G, Cicchini E, Ramacieri G, Pelleri MC, Vitale L, Strippoli P, Locatelli C, Cocchi G, Piovesan A, and Caracausi M
Subjects: Amplified Fragment Length Polymorphism Analysis standards, Genome-Wide Association Study standards, Humans, Amplified Fragment Length Polymorphism Analysis methods, Genome-Wide Association Study methods, Methylenetetrahydrofolate Reductase (NADPH2) genetics, Polymorphism, Single Nucleotide
Abstract: Background: 5,10-Methylentetrahydrofolate reductase (MTHFR) C677T polymorphism is one of the most studied genetic variations in the human genome. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) is one of the most used techniques to characterize the point mutations in genomic sequences because of its suitability and low cost. The most widely used method for the MTHFR C677T polymorphism characterization was developed by Frosst et al. (1995) but appears to have some technical limitations. The aim of this study was to propose a novel PCR-RFLP method for the detection of this polymorphism., Methods: In order to retrieve all published articles possibly describing any PCR-RFLP methods useful to analyze MTHFR C677T polymorphism, we performed systematic queries on PubMed, using a combination of Boolean operators (AND/OR) and MeSH terms. Amplify software was used in order to design a new primer pair following the optimal standard criteria. Primer-BLAST software was used to check primer pair's biological specificity., Results: The analysis of previous literature showed that PCR-RFLP method remains the most used technique. None of the 108 primer pairs described was ideal with regard to main accepted primer pair biochemical technical parameters. The new primer pair amplifies a DNA-fragment of 513 base pair (bp) that, in the presence of the polymorphism, is cut by Hinf I enzyme in two pieces of 146 bp and 367 bp and clearly visible on 2% agarose gel. The level of expertise and the materials required are minimal and the protocol takes one day to carry out., Conclusion: Our original PCR-RFLP strategy, specifically designed to make the analysis optimal with respect to PCR primers and gel analysis, fits the ideal criteria compared to the widely used strategy by Frosst et al (1995) as well as any other PCR-RFLP strategies proposed for MTHFR C677T polymorphism genotyping to date., (© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)
Published: 2019
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28. Dataset of differential gene expression between total normal human thyroid and histologically normal thyroid adjacent to papillary thyroid carcinoma.

Author: Vitale L, Piovesan A, Antonaros F, Strippoli P, Pelleri MC, and Caracausi M
Abstract: This article contains further data and information from our published manuscript [1]. We aim to identify significant transcriptome alterations of total normal human thyroid vs. histologically normal thyroid adjacent to papillary thyroid carcinoma. We performed a systematic meta-analysis of all the available gene expression profiles for the whole organ also collecting gene expression data for the normal thyroid adjacent to papillary thyroid carcinoma. A differential quantitative transcriptome reference map was generated by using TRAM (Transcriptome Mapper) software able to combine, normalize and integrate a total of 35 datasets from total normal thyroid and 40 datasets from histologically normal thyroid adjacent to papillary thyroid carcinoma from different sources. This analysis identified genes and genome segments that significantly discriminated the two groups of samples. Differentially expressed genes were grouped and enrichment function analyses were performed identifying the main features of the differentially expressed genes between total normal thyroid and histologically normal thyroid adjacent to papillary thyroid carcinoma. The search for housekeeping genes retrieved 414 loci.
Published: 2019
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29. On the length, weight and GC content of the human genome.

Author: Piovesan A, Pelleri MC, Antonaros F, Strippoli P, Caracausi M, and Vitale L
Subjects: Female, Humans, Male, Base Composition, DNA, Mitochondrial, Genome, Human, Genomics
Abstract: Objective: Basic parameters commonly used to describe genomes including length, weight and relative guanine-cytosine (GC) content are widely cited in absence of a primary source. By using updated data and original software we determined these values to the best of our knowledge as standard reference for the whole human nuclear genome, for each chromosome and for mitochondrial DNA. We also devised a method to calculate the relative GC content in the whole messenger RNA sequence set and in transcriptomes by multiplying the GC content of each gene by its mean expression level., Results: The male nuclear diploid genome extends for 6.27 Gigabase pairs (Gbp), is 205.00 cm (cm) long and weighs 6.41 picograms (pg). Female values are 6.37 Gbp, 208.23 cm, 6.51 pg. The individual variability and the implication for the DNA informational density in terms of bits/volume were discussed. The genomic GC content is 40.9%. Following analysis in different transcriptomes and species, we showed that the greatest deviation was observed in the pathological condition analysed (trisomy 21 leukaemic cells) and in Caenorhabditis elegans. Our results may represent a solid basis for further investigation on human structural and functional genomics while also providing a framework for other genome comparative analysis.
Published: 2019
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30. Integrated Quantitative Transcriptome Maps of Human Trisomy 21 Tissues and Cells.

Author: Pelleri MC, Cattani C, Vitale L, Antonaros F, Strippoli P, Locatelli C, Cocchi G, Piovesan A, and Caracausi M
Abstract: Down syndrome (DS) is due to the presence of an extra full or partial chromosome 21 (Hsa21). The identification of genes contributing to DS pathogenesis could be the key to any rational therapy of the associated intellectual disability. We aim at generating quantitative transcriptome maps in DS integrating all gene expression profile datasets available for any cell type or tissue, to obtain a complete model of the transcriptome in terms of both expression values for each gene and segmental trend of gene expression along each chromosome. We used the TRAM (Transcriptome Mapper) software for this meta-analysis, comparing transcript expression levels and profiles between DS and normal brain, lymphoblastoid cell lines, blood cells, fibroblasts, thymus and induced pluripotent stem cells, respectively. TRAM combined, normalized, and integrated datasets from different sources and across diverse experimental platforms. The main output was a linear expression value that may be used as a reference for each of up to 37,181 mapped transcripts analyzed, related to both known genes and expression sequence tag (EST) clusters. An independent example in vitro validation of fibroblast transcriptome map data was performed through "Real-Time" reverse transcription polymerase chain reaction showing an excellent correlation coefficient ( r = 0.93, p < 0.0001) with data obtained in silico . The availability of linear expression values for each gene allowed the testing of the gene dosage hypothesis of the expected 3:2 DS/normal ratio for Hsa21 as well as other human genes in DS, in addition to listing genes differentially expressed with statistical significance. Although a fraction of Hsa21 genes escapes dosage effects, Hsa21 genes are selectively over-expressed in DS samples compared to genes from other chromosomes, reflecting a decisive role in the pathogenesis of the syndrome. Finally, the analysis of chromosomal segments reveals a high prevalence of Hsa21 over-expressed segments over the other genomic regions, suggesting, in particular, a specific region on Hsa21 that appears to be frequently over-expressed (21q22). Our complete datasets are released as a new framework to investigate transcription in DS for individual genes as well as chromosomal segments in different cell types and tissues.
Published: 2018
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31. Plasma and urinary metabolomic profiles of Down syndrome correlate with alteration of mitochondrial metabolism.

Author: Caracausi M, Ghini V, Locatelli C, Mericio M, Piovesan A, Antonaros F, Pelleri MC, Vitale L, Vacca RA, Bedetti F, Mimmi MC, Luchinat C, Turano P, Strippoli P, and Cocchi G
Subjects: Adolescent, Adult, Child, Child, Preschool, Citric Acid Cycle, Cohort Studies, Down Syndrome genetics, Female, Gene Dosage genetics, Humans, Magnetic Resonance Spectroscopy, Male, Multivariate Analysis, Siblings, Young Adult, Blood Proteins metabolism, Chromosomes, Human, Pair 21 genetics, Down Syndrome metabolism, Metabolome, Mitochondria metabolism, Urine chemistry
Abstract: Down syndrome (DS) is caused by the presence of a supernumerary copy of the human chromosome 21 (Hsa21) and is the most frequent genetic cause of intellectual disability (ID). Key traits of DS are the distinctive facies and cognitive impairment. We conducted for the first time an analysis of the Nuclear Magnetic Resonance (NMR)-detectable part of the metabolome in plasma and urine samples, studying 67 subjects with DS and 29 normal subjects as controls selected among DS siblings. Multivariate analysis of the NMR metabolomic profiles showed a clear discrimination (up to of 80% accuracy) between the DS and the control groups. The univariate analysis of plasma and urine revealed a significant alteration for some interesting metabolites. Remarkably, most of the altered concentrations were consistent with the 3:2 gene dosage model, suggesting effects caused by the presence of three copies of Hsa21 rather than two: DS/normal ratio in plasma was 1.23 (pyruvate), 1.47 (succinate), 1.39 (fumarate), 1.33 (lactate), 1.4 (formate). Several significantly altered metabolites are produced at the beginning or during the Krebs cycle. Accounting for sex, age and fasting state did not significantly affect the main result of both multivariate and univariate analysis.
Published: 2018
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32. Genotype-phenotype correlation for congenital heart disease in Down syndrome through analysis of partial trisomy 21 cases.

Author: Pelleri MC, Gennari E, Locatelli C, Piovesan A, Caracausi M, Antonaros F, Rocca A, Donati CM, Conti L, Strippoli P, Seri M, Vitale L, and Cocchi G
Subjects: Amyloid Precursor Protein Secretases genetics, Aspartic Acid Endopeptidases genetics, Cell Adhesion Molecules genetics, Genetic Association Studies, Humans, Pregnancy Proteins genetics, RNA, Long Noncoding genetics, Chromosome Mapping methods, Chromosomes, Human, Pair 21 genetics, Down Syndrome complications, Genetic Predisposition to Disease, Heart Defects, Congenital genetics
Abstract: Among Down syndrome (DS) children, 40-50% have congenital heart disease (CHD). Although trisomy 21 is not sufficient to cause CHD, three copies of at least part of chromosome 21 (Hsa21) increases the risk for CHD. In order to establish a genotype-phenotype correlation for CHD in DS, we built an integrated Hsa21 map of all described partial trisomy 21 (PT21) cases with sufficient indications regarding presence or absence of CHD (n=107), focusing on DS PT21 cases. We suggest a DS CHD candidate region on 21q22.2 (0.96Mb), being shared by most PT21 cases with CHD and containing three known protein-coding genes (DSCAM, BACE2, PLAC4) and four known non-coding RNAs (DSCAM-AS1, DSCAM-IT1, LINC00323, MIR3197). The characterization of a DS CHD candidate region provides a useful approach to identify specific genes contributing to the pathology and to orient further investigations and possibly more effective therapy in relation to the multifactorial pathogenesis of CHD., (Copyright © 2017 Elsevier Inc. All rights reserved.)
Published: 2017
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33. A molecular view of the normal human thyroid structure and function reconstructed from its reference transcriptome map.

Author: Vitale L, Piovesan A, Antonaros F, Strippoli P, Pelleri MC, and Caracausi M
Subjects: Databases, Genetic, Female, Genes, Essential genetics, Humans, Male, Mutation, Organ Specificity, Phenotype, Reference Standards, Thyroid Gland physiology, Gene Expression Profiling standards, Thyroid Gland metabolism
Abstract: Background: The thyroid is the earliest endocrine structure to appear during human development, and thyroid hormones are necessary for proper organism development, in particular for the nervous system and heart, normal growth and skeletal maturation. To date a quantitative, validated transcriptional atlas of the whole normal human thyroid does not exist and the availability of a detailed expression map might be an excellent occasion to investigate the many features of the thyroid transcriptome., Results: We present a view at the molecular level of the normal human thyroid histology and physiology obtained by a systematic meta-analysis of all the available gene expression profiles for the whole organ. A quantitative transcriptome reference map was generated by using the TRAM (Transcriptome Mapper) software able to combine, normalize and integrate a total of 35 suitable datasets from different sources thus providing a typical reference expression value for each of the 27,275 known, mapped transcripts obtained. The experimental in vitro validation of data was performed by "Real-Time" reverse transcription polymerase chain reaction showing an excellent correlation coefficient (r = 0.93) with data obtained in silico., Conclusions: Our study provides a quantitative global reference portrait of gene expression in the normal human thyroid and highlights differential expression between normal human thyroid and a pool of non-thyroid tissues useful for modeling correlations between thyroidal gene expression and specific thyroid functions and diseases. The experimental in vitro validation supports the possible usefulness of the human thyroid transcriptome map as a reference for molecular studies of the physiology and pathology of this organ.
Published: 2017
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34. Systematic identification of human housekeeping genes possibly useful as references in gene expression studies.

Author: Caracausi M, Piovesan A, Antonaros F, Strippoli P, Vitale L, and Pelleri MC
Subjects: Adult, Databases, Genetic, Gene Expression, Humans, Gene Expression Profiling methods, Genes, Essential, Genomics methods, Transcriptome
Abstract: The ideal reference, or control, gene for the study of gene expression in a given organism should be expressed at a medium‑high level for easy detection, should be expressed at a constant/stable level throughout different cell types and within the same cell type undergoing different treatments, and should maintain these features through as many different tissues of the organism. From a biological point of view, these theoretical requirements of an ideal reference gene appear to be best suited to housekeeping (HK) genes. Recent advancements in the quality and completeness of human expression microarray data and in their statistical analysis may provide new clues toward the quantitative standardization of human gene expression studies in biology and medicine, both cross‑ and within‑tissue. The systematic approach used by the present study is based on the Transcriptome Mapper tool and exploits the automated reassignment of probes to corresponding genes, intra‑ and inter‑sample normalization, elaboration and representation of gene expression values in linear form within an indexed and searchable database with a graphical interface recording quantitative levels of expression, expression variability and cross‑tissue width of expression for more than 31,000 transcripts. The present study conducted a meta‑analysis of a pool of 646 expression profile data sets from 54 different human tissues and identified actin γ 1 as the HK gene that best fits the combination of all the traditional criteria to be used as a reference gene for general use; two ribosomal protein genes, RPS18 and RPS27, and one aquaporin gene, POM121 transmembrane nucleporin C, were also identified. The present study provided a list of tissue‑ and organ‑specific genes that may be most suited for the following individual tissues/organs: Adipose tissue, bone marrow, brain, heart, kidney, liver, lung, ovary, skeletal muscle and testis; and also provides in these cases a representative, quantitative portrait of the relative, typical gene‑expression profile in the form of searchable database tables.
Published: 2017
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35. Difficulty in obtaining the complete mRNA coding sequence at 5' region (5' end mRNA artifact): Causes, consequences in biology and medicine and possible solutions for obtaining the actual amino acid sequence of proteins (Review).

Author: Vitale L, Caracausi M, Casadei R, Pelleri MC, and Piovesan A
Subjects: Amino Acid Sequence, Animals, Artifacts, Base Sequence, DNA, Complementary chemistry, DNA, Complementary genetics, Humans, RNA, Messenger chemistry, Reverse Transcription, Sequence Analysis, DNA methods, Sequence Analysis, DNA standards, Open Reading Frames, RNA, Messenger genetics
Abstract: The known difficulty in obtaining the actual full length, complete sequence of a messenger RNA (mRNA) may lead to the erroneous determination of its coding sequence at the 5' region (5' end mRNA artifact), and consequently to the wrong assignment of the translation start codon, leading to the inaccurate prediction of the encoded polypeptide at its amino terminus. Among the known human genes whose study was affected by this artifact, we can include disco interacting protein 2 homolog A (DIP2A; KIAA0184), Down syndrome critical region 1 (DSCR1), SON DNA binding protein (SON), trefoil factor 3 (TFF3) and URB1 ribosome biogenesis 1 homolog (URB1; KIAA0539) on chromosome 21, as well as receptor for activated C kinase 1 (RACK1, also known as GNB2L1), glutaminyl‑tRNA synthetase (QARS) and tyrosyl-DNA phosphodiesterase 2 (TDP2) along with another 474 loci, including interleukin 16 (IL16). In this review, we discuss the causes of this issue, its quantitative incidence in biomedical research, the consequences in biology and medicine, and the possible solutions for obtaining the actual amino acid sequence of proteins in the post-genomics era.
Published: 2017
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36. Integrated Transcriptome Map Highlights Structural and Functional Aspects of the Normal Human Heart.

Author: Caracausi M, Piovesan A, Vitale L, and Pelleri MC
Subjects: Databases as Topic, Gene Expression Profiling, Gene Expression Regulation, Genes, Essential, Humans, Mutation genetics, Phenotype, Real-Time Polymerase Chain Reaction, Reproducibility of Results, Software, Heart anatomy & histology, Heart physiology, Transcriptome genetics
Abstract: A systematic meta-analysis of the available gene expression profiling datasets for the whole normal human heart generated a quantitative transcriptome reference map of this organ. Transcriptome Mapper (TRAM) software integrated 32 gene expression profile datasets from different sources returning a reference value of expression for each of the 43,360 known, mapped transcripts assayed by any of the experimental platforms used in this regard. Main findings include the visualization at the gene and chromosomal levels of the classical description of the basic histology and physiology of the heart, the identification of suitable housekeeping reference genes, the analysis of stoichiometry of gene products, and the focusing on chromosome 21 genes, which are present in one excess copy in Down syndrome subjects, presenting cardiovascular defects in 30-40% of cases. Independent in vitro validation showed an excellent correlation coefficient (r = 0.98) with the in silico data. Remarkably, heart/non-cardiac tissue expression ratio may also be used to anticipate that effects of mutations will most probably affect or not the heart. The quantitative reference global portrait of gene expression in the whole normal human heart illustrates the structural and functional aspects of the whole organ and is a general model to understand the mechanisms underlying heart pathophysiology. J. Cell. Physiol. 232: 759-770, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)
Published: 2017
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37. GeneBase 1.1: a tool to summarize data from NCBI gene datasets and its application to an update of human gene statistics.

Author: Piovesan A, Caracausi M, Antonaros F, Pelleri MC, and Vitale L
Subjects: Humans, National Library of Medicine (U.S.), United States, Databases, Nucleic Acid, Genome, Human, Sequence Analysis, DNA methods, Software
Abstract: We release GeneBase 1.1, a local tool with a graphical interface useful for parsing, structuring and indexing data from the National Center for Biotechnology Information (NCBI) Gene data bank. Compared to its predecessor GeneBase (1.0), GeneBase 1.1 now allows dynamic calculation and summarization in terms of median, mean, standard deviation and total for many quantitative parameters associated with genes, gene transcripts and gene features (exons, introns, coding sequences, untranslated regions). GeneBase 1.1 thus offers the opportunity to perform analyses of the main gene structure parameters also following the search for any set of genes with the desired characteristics, allowing unique functionalities not provided by the NCBI Gene itself. In order to show the potential of our tool for local parsing, structuring and dynamic summarizing of publicly available databases for data retrieval, analysis and testing of biological hypotheses, we provide as a sample application a revised set of statistics for human nuclear genes, gene transcripts and gene features. In contrast with previous estimations strongly underestimating the length of human genes, a 'mean' human protein-coding gene is 67 kbp long, has eleven 309 bp long exons and ten 6355 bp long introns. Median, mean and extreme values are provided for many other features offering an updated reference source for human genome studies, data useful to set parameters for bioinformatic tools and interesting clues to the biomedical meaning of the gene features themselves.Database URL: http://apollo11.isto.unibo.it/software/., (© The Author(s) 2016. Published by Oxford University Press.)
Published: 2016
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38. Meta-Analysis of Parkinson's Disease Transcriptome Data Using TRAM Software: Whole Substantia Nigra Tissue and Single Dopamine Neuron Differential Gene Expression.

Author: Mariani E, Frabetti F, Tarozzi A, Pelleri MC, Pizzetti F, and Casadei R
Subjects: Humans, Dopaminergic Neurons metabolism, Parkinson Disease genetics, Software, Substantia Nigra metabolism, Transcriptome genetics
Abstract: The understanding of the genetic basis of the Parkinson's disease (PD) and the correlation between genotype and phenotype has revolutionized our knowledge about the pathogenetic mechanisms of neurodegeneration, opening up exciting new therapeutic and neuroprotective perspectives. Genomic knowledge of PD is still in its early stages and can provide a good start for studies of the molecular mechanisms that underlie the gene expression variations and the epigenetic mechanisms that may contribute to the complex and characteristic phenotype of PD. In this study we used the software TRAM (Transcriptome Mapper) to analyse publicly available microarray data of a total of 151 PD patients and 130 healthy controls substantia nigra (SN) samples, to identify chromosomal segments and gene loci differential expression. In particular, we separately analyzed PD patients and controls data from post-mortem snap-frozen SN whole tissue and from laser microdissected midbrain dopamine (DA) neurons, to better characterize the specific DA neuronal expression profile associated with the late-stage Parkinson's condition. The default "Map" mode analysis resulted in 10 significantly over/under-expressed segments, mapping on 8 different chromosomes for SN whole tissue and in 4 segments mapping on 4 different chromosomes for DA neurons. In conclusion, TRAM software allowed us to confirm the deregulation of some genomic regions and loci involved in key molecular pathways related to neurodegeneration, as well as to provide new insights about genes and non-coding RNA transcripts not yet associated with the disease., Competing Interests: The authors have declared that no competing interests exist.
Published: 2016
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39. Systematic reanalysis of partial trisomy 21 cases with or without Down syndrome suggests a small region on 21q22.13 as critical to the phenotype.

Author: Pelleri MC, Cicchini E, Locatelli C, Vitale L, Caracausi M, Piovesan A, Rocca A, Poletti G, Seri M, Strippoli P, and Cocchi G
Subjects: Chromosome Mapping, Chromosomes, Human, Pair 21 genetics, Down Syndrome pathology, Female, Genetic Association Studies, Genotype, Humans, Male, Trisomy pathology, DNA Copy Number Variations genetics, Down Syndrome genetics, Trisomy genetics
Abstract: A 'Down Syndrome critical region' (DSCR) sufficient to induce the most constant phenotypes of Down syndrome (DS) had been identified by studying partial (segmental) trisomy 21 (PT21) as an interval of 0.6-8.3 Mb within human chromosome 21 (Hsa21), although its existence was later questioned. We propose an innovative, systematic reanalysis of all described PT21 cases (from 1973 to 2015). In particular, we built an integrated, comparative map from 125 cases with or without DS fulfilling stringent cytogenetic and clinical criteria. The map allowed to define or exclude as candidates for DS fine Hsa21 sequence intervals, also integrating duplication copy number variants (CNVs) data. A highly restricted DSCR (HR-DSCR) of only 34 kb on distal 21q22.13 has been identified as the minimal region whose duplication is shared by all DS subjects and is absent in all non-DS subjects. Also being spared by any duplication CNV in healthy subjects, HR-DSCR is proposed as a candidate for the typical DS features, the intellectual disability and some facial phenotypes. HR-DSCR contains no known gene and has relevant homology only to the chimpanzee genome. Searching for HR-DSCR functional loci might become a priority for understanding the fundamental genotype-phenotype relationships in DS., (© The Author 2016. Published by Oxford University Press.)
Published: 2016
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40. A quantitative transcriptome reference map of the normal human hippocampus.

Author: Caracausi M, Rigon V, Piovesan A, Strippoli P, Vitale L, and Pelleri MC
Subjects: Databases, Factual, Female, Gene Expression, Humans, Male, Microarray Analysis methods, Polymerase Chain Reaction, Sex Characteristics, Software, Hippocampus metabolism, Transcriptome
Abstract: We performed an innovative systematic meta-analysis of 41 gene expression profiles of normal human hippocampus to provide a quantitative transcriptome reference map of it, i.e. a reference typical value of expression for each of the 30,739 known mapped and the 16,258 uncharacterized (unmapped) transcripts. For this aim, we used the software called TRAM (Transcriptome Mapper), which is able to generate transcriptome maps based on gene expression data from multiple sources. We also analyzed differential expression by comparing the hippocampus with the whole brain transcriptome map to identify a typical expression pattern of this subregion compared with the whole organ. Finally, due to the fact that the hippocampus is one of the main brain region to be severely affected in trisomy 21 (the best known genetic cause of intellectual disability), a particular attention was paid to the expression of chromosome 21 (chr21) genes. Data were downloaded from microarray databases, processed, and analyzed using TRAM software. Among the main findings, the most over-expressed loci in the hippocampus are the expressed sequence tag cluster Hs.732685 and the member of the calmodulin gene family CALM2. The tubulin folding cofactor B (TBCB) gene is the best gene at behaving like a housekeeping gene. The hippocampus vs. the whole brain differential transcriptome map shows the over-expression of LINC00114, a long non-coding RNA mapped on chr21. The hippocampus transcriptome map was validated in vitro by assaying gene expression through several magnitude orders by "Real-Time" reverse transcription polymerase chain reaction (RT-PCR). The highly significant agreement between in silico and experimental data suggested that our transcriptome map may be a useful quantitative reference benchmark for gene expression studies related to human hippocampus. Furthermore, our analysis yielded biological insights about those genes that have an intrinsic over-/under-expression in the hippocampus., (© 2015 Wiley Periodicals, Inc.)
Published: 2016
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41. Identification of minimal eukaryotic introns through GeneBase, a user-friendly tool for parsing the NCBI Gene databank.

Author: Piovesan A, Caracausi M, Ricci M, Strippoli P, Vitale L, and Pelleri MC
Subjects: Algorithms, Genomics, Hepatocyte Growth Factor genetics, Humans, Proto-Oncogene Proteins genetics, User-Computer Interface, Databases, Genetic, Databases, Nucleic Acid, Introns
Abstract: We have developed GeneBase, a full parser of the National Center for Biotechnology Information (NCBI) Gene database, which generates a fully structured local database with an intuitive user-friendly graphic interface for personal computers. Features of all the annotated eukaryotic genes are accessible through three main software tables, including for each entry details such as the gene summary, the gene exon/intron structure and the specific Gene Ontology attributions. The structuring of the data, the creation of additional calculation fields and the integration with nucleotide sequences allow users to make many types of comparisons and calculations that are useful for data retrieval and analysis. We provide an original example analysis of the existing introns across all the available species, through which the classic biological problem of the 'minimal intron' may find a solution using available data. Based on all currently available data, we can define the shortest known eukaryotic GT-AG intron length, setting the physical limit at the 30 base pair intron belonging to the human MST1L gene. This 'model intron' will shed light on the minimal requirement elements of recognition used for conventional splicing functioning. Remarkably, this size is indeed consistent with the sum of the splicing consensus sequence lengths., (© The Author 2015. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.)
Published: 2015
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42. Integrated differential transcriptome maps of Acute Megakaryoblastic Leukemia (AMKL) in children with or without Down Syndrome (DS).

Author: Pelleri MC, Piovesan A, Caracausi M, Berardi AC, Vitale L, and Strippoli P
Subjects: Case-Control Studies, Cells, Cultured, Child, Humans, Leukemia, Megakaryoblastic, Acute etiology, Luciferases metabolism, Megakaryocyte Progenitor Cells cytology, Oligonucleotide Array Sequence Analysis, RNA, Messenger genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Biomarkers, Tumor genetics, Databases, Factual, Down Syndrome complications, Gene Expression Profiling, Leukemia, Megakaryoblastic, Acute diagnosis, Megakaryocyte Progenitor Cells metabolism
Abstract: Background: The incidence of Acute Megakaryoblastic Leukemia (AMKL) is 500-fold higher in children with Down Syndrome (DS) compared with non-DS children, but the relevance of trisomy 21 as a specific background of AMKL in DS is still an open issue. Several Authors have determined gene expression profiles by microarray analysis in DS and/or non-DS AMKL. Due to the rarity of AMKL, these studies were typically limited to a small group of samples., Methods: We generated integrated quantitative transcriptome maps by systematic meta-analysis from any available gene expression profile dataset related to AMKL in pediatric age. This task has been accomplished using a tool recently described by us for the generation and the analysis of quantitative transcriptome maps, TRAM (Transcriptome Mapper), which allows effective integration of data obtained from different experimenters, experimental platforms and data sources. This allowed us to explore gene expression changes involved in transition from normal megakaryocytes (MK, n=19) to DS (n=43) or non-DS (n=45) AMKL blasts, including the analysis of Transient Myeloproliferative Disorder (TMD, n=20), a pre-leukemia condition., Results: We propose a biological model of the transcriptome depicting progressive changes from MK to TMD and then to DS AMKL. The data indicate the repression of genes involved in MK differentiation, in particular the cluster on chromosome 4 including PF4 (platelet factor 4) and PPBP (pro-platelet basic protein); the gene for the mitogen-activated protein kinase MAP3K10 and the thrombopoietin receptor gene MPL. Moreover, comparing both DS and non-DS AMKL with MK, we identified three potential clinical markers of progression to AMKL: TMEM241 (transmembrane protein 241) was the most over-expressed single gene, while APOC2 (apolipoprotein C-II) and ZNF587B (zinc finger protein 587B) appear to be the most discriminant markers of progression, specifically to DS AMKL. Finally, the chromosome 21 (chr21) genes resulted to be the most over-expressed in DS and non-DS AMKL, as well as in TMD, pointing out a key role of chr21 genes in differentiating AMKL from MK., Conclusions: Our study presents an integrated original model of the DS AMLK transcriptome, providing the identification of genes relevant for its pathophysiology which can potentially be new clinical markers.
Published: 2014
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43. A quantitative transcriptome reference map of the normal human brain.

Author: Caracausi M, Vitale L, Pelleri MC, Piovesan A, Bruno S, and Strippoli P
Subjects: Adult, Databases, Factual, Female, Fetus metabolism, Humans, Male, Sex Factors, Brain metabolism, Gene Expression Profiling
Abstract: We performed an innovative systematic meta-analysis of 60 gene expression profiles of whole normal human brain, to provide a quantitative transcriptome reference map of it, i.e. a reference typical value of expression for each of the 39,250 known, mapped and 26,026 uncharacterized (unmapped) transcripts. To this aim, we used the software named Transcriptome Mapper (TRAM), which is able to generate transcriptome maps based on gene expression data from multiple sources. We also analyzed differential expression by comparing the brain transcriptome with those derived from human foetal brain gene expression, from a pool of human tissues (except the brain) and from the two normal human brain regions cerebellum and cerebral cortex, which are two of the main regions severely affected when cognitive impairment occurs, as happens in the case of trisomy 21. Data were downloaded from microarray databases, processed and analyzed using TRAM software and validated in vitro by assaying gene expression through several magnitude orders by 'real-time' reverse transcription polymerase chain reaction (RT-PCR). The excellent agreement between in silico and experimental data suggested that our transcriptome maps may be a useful quantitative reference benchmark for gene expression studies related to the human brain. Furthermore, our analysis yielded biological insights about those genes which have an intrinsic over-/under-expression in the brain, in addition offering a basis for the regional analysis of gene expression. This could be useful for the study of chromosomal alterations associated to cognitive impairment, such as trisomy 21, the most common genetic cause of intellectual disability.
Published: 2014
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44. Characterization of human gene locus CYYR1: a complex multi-transcript system.

Author: Casadei R, Pelleri MC, Vitale L, Facchin F, Canaider S, Strippoli P, Vian M, Piovesan A, Bianconi E, Mariani E, Piva F, and Frabetti F
Subjects: Amino Acid Sequence, Computer Simulation, Exons, Gene Expression, Genes, Genetic Loci, Humans, Molecular Sequence Data, Organ Specificity, Protein Isoforms genetics, Alternative Splicing, Membrane Proteins genetics
Abstract: Cysteine/tyrosine-rich 1 (CYYR1) is a gene we previously identified on human chromosome 21 starting from an in-depth bioinformatics analysis of chromosome 21 segment 40/105 (21q21.3), where no coding region had previously been predicted. CYYR1 was initially characterized as a four-exon gene, whose brain-derived cDNA sequencing predicts a 154-amino acid product. In this study we provide, with in silico and in vitro analyses, the first detailed description of the human CYYR1 locus. The analysis of this locus revealed that it is composed of a multi-transcript system, which includes at least seven CYYR1 alternative spliced isoforms and a new CYYR1 antisense gene (named CYYR1-AS1). In particular, we cloned, for the first time, the following isoforms: CYYR1-1,2,3,4b and CYYR1-1,2,3b, which present a different 3' transcribed region, with a consequent different carboxy-terminus of the predicted proteins; CYYR1-1,2,4 lacks exon 3; CYYR1-1,2,2bis,3,4 presents an additional exon between exon 2 and exon 3; CYYR1-1b,2,3,4 presents a different 5' untranslated region when compared to CYYR1. The complexity of the locus is enriched by the presence of an antisense transcript. We have cloned a long transcript overlapping with CYYR1 as an antisense RNA, probably a non-coding RNA. Expression analysis performed in different normal tissues, tumour cell lines as well as in trisomy 21 and euploid fibroblasts has confirmed a quantitative and qualitative variability in the expression pattern of the multi-transcript locus, suggesting a possible role in complex diseases that should be further investigated.
Published: 2014
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45. Improving mRNA 5' coding sequence determination in the mouse genome.

Author: Piovesan A, Caracausi M, Pelleri MC, Vitale L, Martini S, Bassani C, Gurioli A, Casadei R, Soldà G, and Strippoli P
Subjects: 5' Flanking Region genetics, Animals, Base Sequence, Cloning, Molecular, Molecular Sequence Data, Sequence Analysis, DNA, Computational Biology methods, Databases, Genetic, Genome genetics, Mice genetics, Open Reading Frames genetics, RNA, Messenger genetics
Abstract: The incomplete determination of the mRNA 5' end sequence may lead to the incorrect assignment of the first AUG codon and to errors in the prediction of the encoded protein product. Due to the significance of the mouse as a model organism in biomedical research, we performed a systematic identification of coding regions at the 5' end of all known mouse mRNAs, using an automated expressed sequence tag (EST)-based approach which we have previously described. By parsing almost 4 million BLAT alignments we found 351 mouse loci, out of 20,221 analyzed, in which an extension of the mRNA 5' coding region was identified. Proof-of-concept confirmation was obtained by in vitro cloning and sequencing for Apc2 and Mknk2 cDNAs. We also generated a list of 16,330 mouse mRNAs where the presence of an in-frame stop codon upstream of the known start codon indicates completeness of the coding sequence at 5' end in the current form. Systematic searches in the main mouse genome databases and genome browsers showed that 82% of our results are original and have not been identified by their annotation pipelines. Moreover, the same information is not easily derivable from RNA-Seq data, due to short sequence length and laboriousness in building full-length transcript structures. In conclusion, our results improve the determination of full-length 5' coding sequences and might be useful in order to reduce errors when studying mouse gene structure and function in biomedical research.
Published: 2014
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46. An estimation of the number of cells in the human body.

Author: Bianconi E, Piovesan A, Facchin F, Beraudi A, Casadei R, Frabetti F, Vitale L, Pelleri MC, Tassani S, Piva F, Perez-Amodio S, Strippoli P, and Canaider S
Subjects: Adult, Cell Size, Humans, Models, Biological, Organ Specificity, Cell Count
Abstract: Background: All living organisms are made of individual and identifiable cells, whose number, together with their size and type, ultimately defines the structure and functions of an organism. While the total cell number of lower organisms is often known, it has not yet been defined in higher organisms. In particular, the reported total cell number of a human being ranges between 10(12) and 10(16) and it is widely mentioned without a proper reference., Aim: To study and discuss the theoretical issue of the total number of cells that compose the standard human adult organism., Subjects and Methods: A systematic calculation of the total cell number of the whole human body and of the single organs was carried out using bibliographical and/or mathematical approaches., Results: A current estimation of human total cell number calculated for a variety of organs and cell types is presented. These partial data correspond to a total number of 3.72 × 10(13)., Conclusions: Knowing the total cell number of the human body as well as of individual organs is important from a cultural, biological, medical and comparative modelling point of view. The presented cell count could be a starting point for a common effort to complete the total calculation.
Published: 2013
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47. Parallel evolution of chordate cis-regulatory code for development.

Author: Doglio L, Goode DK, Pelleri MC, Pauls S, Frabetti F, Shimeld SM, Vavouri T, and Elgar G
Subjects: Animals, Conserved Sequence, Gene Expression Regulation, Urochordata, Vertebrates genetics, Ciona intestinalis genetics, Evolution, Molecular, Gene Regulatory Networks, Zebrafish genetics
Abstract: Urochordates are the closest relatives of vertebrates and at the larval stage, possess a characteristic bilateral chordate body plan. In vertebrates, the genes that orchestrate embryonic patterning are in part regulated by highly conserved non-coding elements (CNEs), yet these elements have not been identified in urochordate genomes. Consequently the evolution of the cis-regulatory code for urochordate development remains largely uncharacterised. Here, we use genome-wide comparisons between C. intestinalis and C. savignyi to identify putative urochordate cis-regulatory sequences. Ciona conserved non-coding elements (ciCNEs) are associated with largely the same key regulatory genes as vertebrate CNEs. Furthermore, some of the tested ciCNEs are able to activate reporter gene expression in both zebrafish and Ciona embryos, in a pattern that at least partially overlaps that of the gene they associate with, despite the absence of sequence identity. We also show that the ability of a ciCNE to up-regulate gene expression in vertebrate embryos can in some cases be localised to short sub-sequences, suggesting that functional cross-talk may be defined by small regions of ancestral regulatory logic, although functional sub-sequences may also be dispersed across the whole element. We conclude that the structure and organisation of cis-regulatory modules is very different between vertebrates and urochordates, reflecting their separate evolutionary histories. However, functional cross-talk still exists because the same repertoire of transcription factors has likely guided their parallel evolution, exploiting similar sets of binding sites but in different combinations., Competing Interests: The authors have declared that no competing interests exist.
Published: 2013
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48. Universal tight correlation of codon bias and pool of RNA codons (codonome): The genome is optimized to allow any distribution of gene expression values in the transcriptome from bacteria to humans.

Author: Piovesan A, Vitale L, Pelleri MC, and Strippoli P
Subjects: Amino Acyl-tRNA Synthetases genetics, Animals, Base Sequence, Brain metabolism, Caenorhabditis elegans genetics, Databases, Nucleic Acid, Erythrocytes metabolism, Escherichia coli genetics, Gene Expression Regulation, Genome, Bacterial, Genome, Human, Humans, Models, Genetic, Saccharomyces cerevisiae genetics, Zebrafish genetics, Codon genetics, Software, Transcriptome
Abstract: Codon bias is the phenomenon in which distinct synonymous codons are used with different frequencies. We define here the "codonome value" as the total number of codons present across all the expressed mRNAs in a given biological condition. We have developed the "CODONOME" software, which calculates the codon bias and, following integration with a gene expression profile, estimates the actual frequency of each codon at the transcriptome level (codonome bias) of a given tissue. Systematic analysis across different human tissues and multiple species shows a surprisingly tight correlation between the codon bias and the codonome bias. An aneuploidy and cancer condition such as that of Down Syndrome-related acute megakaryoblastic leukemia (DS-AMKL), does not appear to alter this relationship. The law of correlation between codon bias and codonome emerges as a property of the distribution and range of the number, sequence and expression level of the genes in a genome., (Copyright © 2013 Elsevier Inc. All rights reserved.)
Published: 2013
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49. Genome-scale analysis of human mRNA 5' coding sequences based on expressed sequence tag (EST) database.

Author: Casadei R, Piovesan A, Vitale L, Facchin F, Pelleri MC, Canaider S, Bianconi E, Frabetti F, and Strippoli P
Subjects: Amino Acid Sequence, Cloning, Molecular, Codon, Initiator, Computational Biology, DNA, Complementary, Databases, Genetic, Genetic Loci, Humans, Molecular Sequence Data, Sequence Alignment, Sequence Analysis, DNA, 5' Untranslated Regions genetics, Expressed Sequence Tags, Genetic Association Studies methods, Genome, Human, Open Reading Frames, RNA, Messenger genetics
Abstract: The "5' end mRNA artifact" issue refers to the incorrect assignment of the first AUG codon in an mRNA, due to the incomplete determination of its 5' end sequence. We performed a systematic identification of coding regions at the 5' end of all human known mRNAs, using an automated expressed sequence tag (EST)-based approach. Following parsing of more than 7 million BLAT alignments, we found 477 human loci, out of 18,665 analyzed, in which an extension of the mRNA 5' coding region was identified. Proof-of-concept confirmation was obtained by in vitro cloning and sequencing for GNB2L1, QARS and TDP2 cDNAs, and the consequences for the functional studies of these loci are discussed. We also generated a list of 20,775 human mRNAs where the presence of an in-frame stop codon upstream of the known start codon indicates completeness of the coding sequence at 5' in the current form., (Copyright © 2012 Elsevier Inc. All rights reserved.)
Published: 2012
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50. Identification of housekeeping genes suitable for gene expression analysis in the zebrafish.

Author: Casadei R, Pelleri MC, Vitale L, Facchin F, Lenzi L, Canaider S, Strippoli P, and Frabetti F
Subjects: Animals, Bone and Bones metabolism, Brain metabolism, Eye metabolism, Female, Muscles metabolism, Organ Specificity, Ovary metabolism, RNA, Messenger metabolism, RNA, Messenger standards, Reverse Transcriptase Polymerase Chain Reaction, Skin metabolism, Zebrafish Proteins metabolism, Gene Expression Profiling, RNA, Messenger genetics, Zebrafish genetics, Zebrafish Proteins genetics
Abstract: Housekeeping (HK) genes are constitutively expressed in order to maintain cellular function. They produce the minimal essential transcripts necessary for normal cellular physiology. Wide range expression, stable expression level and high expression level are independent features of a single gene expression and are all desirable for the definition of an "ideal" HK. Recent studies have questioned the possible existence of "ideal" HK mRNAs, mainly because of the wide expression conditions variability. This would imply that for each investigated organism the suitability of a putative HK should be verified. We perform a systematic analysis to identify "optimal" HK genes in Danio rerio (zebrafish), to be used in expression analyses conducted on embryos/larvae at different developmental stages, as well as on differentiated adult tissues from single donors. The expression pattern of candidate genes, selected on the basis of the literature available and of ad hoc bioinformatics analysis, was assessed by quantitative relative RT-PCR in an RNA panel, including six different embryo/larvae developmental stages and six adult tissues. Statistical analysis was performed to identify genes with the lowest expression standard deviation in the studied panel. Our results showed that beta-actin 2 (bactin2) is the mRNA with the lowest variability of expression., (Copyright © 2011 Elsevier B.V. All rights reserved.)
Published: 2011
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