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1. Predictors and associations of the persistent airflow limitation phenotype in asthma: a post-hoc analysis of the ATLANTIS study

Author

Badorrek, P., Broeders, M., Boersma, W.G., Chetta, A., Cukier, A., D'Amato, M., Djukanovic, R., Foschino, M.P., Gessner, C., Hanania, N., Martin, R., Milleri, S., Olivenstein, R., Paggiaro, P., Pizzichini, E., Plaza Moral, V., Postma, D.S., Scichilone, N., Schilz, R., Spanevello, A., Stelmach, R., Vroegop, J.S., Usmani, O.S., Zhang, Q., Ahmed, H., Allen, D., Ballereau, S., Batuwitage, M.K., Bedding, A., Behndig, A.F., Berglind, A., Berton, A., Bigler, J., Boedigheimer, M.J., Bønnelykke, K., Brinkman, P., Bush, A., Campagna, D., Casaulta, C., Chaiboonchoe, A., Davison, T., De Meulder, B., Delin, I., Dennison, P., Dodson, P., El Hadjam, L., Erzen, D., Faulenbach, C., Fichtner, K., Fitch, N., Formaggio, E., Gahlemann, M., Galffy, G., Garissi, D., Garret, T., Guillmant-Farry, E., Henriksson, E., Hoda, U., Hohlfeld, J.M., Hu, X., James, A., Johnson, K., Jullian, N., Kerry, G., Klüglich, M., Knowles, R., Konradsen, J.R., Kretsos, K., Krueger, L., Lantz, A-S., Larminie, C., Latzin, P., Lefaudeux, D., Lemonnier, N., Lowe, L.A., Lutter, R., Manta, A., Mazein, A., McEvoy, L., Menzies-Gow, A., Mores, N., Murray, C.S., Nething, K., Nihlén, U., Niven, R., Nordlund, B., Nsubuga, S., Pellet, J., Pison, C., Praticò, G., Puig Valls, M., Riemann, K., Rocha, J.P., Rossios, C., Santini, G., Sagi, M., Scott, S., Sehgal, N., Selby, A., Söderman, P., Sogbesan, A., Spycher, F., Stephan, S., Stokholm, J., Sunther, M., Szentkereszty, M., Tamasi, L., Tariq, K., Valente, S, Van Aalderen, W.M., Van Drunen, C.M., Van Eyll, J., Vyas, A., Yu, W., Zetterguist, W., Zolkipli, Z., Zwinderman, A.H., Agusti, A., Wedzicha, J.A., Donaldson, G.C., Faner, R., Breyer-Kohansal, R., Maitland-van der Zee, A.H., Melén, E., Allinson, J.P., Vanfleteren, L.E.G.W., Vestbo, J., Adcock, I.M., Lahousse, L., Van den Berge, M., Alter, P., Barbe, F., Brightling, C.E., Breyer, M.K., Burghuber, O.C., Casas, M., Chung, K.F., Cosío, B.G., Crispi, F., De Batlle, J., Fitting, J.W., Garcia, J., Hallberg, J., Hartl, S., Jarvis, D., Mathioudakis, A., Nicod, L., Papi, A., Ritchie, A., Sigsgaard, T., Sterk, P.J., Ullman, A., Vellvé, K., Vogelmeier, C., Wheelock, A.M., Wheelock, C.E., Kole, Tessa M, Vanden Berghe, Elise, Kraft, Monica, Vonk, Judith M, Nawijn, Martijn C, Siddiqui, Salman, Sun, Kai, Fabbri, Leonardo M, Rabe, Klaus F, Chung, Kian Fan, Nicolini, Gabriele, Papi, Alberto, Brightling, Chris, Singh, Dave, van der Molen, Thys, Dahlén, Sven-Erik, Agusti, Alvar, Faner, Rosa, Wedzicha, Jadwiga A, Donaldson, Gavin C, Adcock, Ian M, Lahousse, Lies, Kerstjens, Huib A M, and van den Berge, Maarten

Published
2023
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3. IL-17–high asthma with features of a psoriasis immunophenotype

Author

Adcock, I.M., Ahmed, H., Auffray, C., Bakke, P., Bansal, A.T., Baribaud, F., Bates, S., Bel, E.H., Bigler, J., Bisgaard, H., Boedigheimer, M.J., Bønnelykke, K., Brandsma, J., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Caruso, M., Chaiboonchoe, A., Chanez, P., Chung, K.F., Compton, C.H., Corfield, J., D'Amico, A., Dahlen, S.E., De Meulder, B., Djukanovic, R., Erpenbeck, V.J., Erzen, D., Fichtner, K., Fitch, N., Fleming, L.J., Formaggio, E., Fowler, S.J., Frey, U., Gahlemann, M., Geiser, T., Guo, Y., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P.W., Higenbottam, T., Hohlfeld, J.M., Holweg, C., Horváth, I., Howarth, P., James, A.J., Knowles, R., Knox, A.J., Krug, N., Lefaudeux, D., Loza, M.J., Lutter, R., Manta, A., Masefield, S., Mazein, A., Meiser, A., Middelveld, R.J.M., Miralpeix, M., Montuschi, P., Mores, N., Murray, C.S., Musial, J., Myles, D., Pahus, L., Pandis, I., Pavlidis, S., Powell, P., Praticò, G., Rao, M. Puig N., Riley, J., Roberts, A., Roberts, G., Rowe, A., Sandström, T., Seibold, W., Selby, A., Shaw, D.E., Sigmund, R., Singer, F., Skipp, P.J., Sousa, A.R., Sterk, P.J., Sun, K., Thornton, B., van Aalderen, W.M., van Geest, M., Vestbo, J., Vissing, N.H., Wagener, A.H., Wagers, S.S., Weiszhart, Z., Wheelock, C.E., Wilson, S.J., Aliprantis, Antonios, Allen, David, Alving, Kjell, Badorrek, P., Balgoma, David, Ballereau, S., Barber, Clair, Batuwitage, Manohara Kanangana, Bautmans, A., Bedding, A., Behndig, A.F., Beleta, Jorge, Berglind, A., Berton, A., Bochenek, Grazyna, Braun, Armin, Campagna, D., Carayannopoulos, Leon, Casaulta, C., Chaleckis, Romanas, Dahlén, B., Davison, imothy, De Alba, Jorge, De Lepeleire, Inge, Dekker, Tamara, Delin, Ingrid, Dennison, P., Dijkhuis, Annemiek, Dodson, Paul, Draper, Aleksandra, Dyson, K., Edwards, Jessica, El Hadjam, L., Emma, Rosalia, Ericsson, Magnus, Faulenbach, C., Flood, Breda, Galffy, G., Gallart, Hector, Garissi, D., Gent, J., Gerhardsson de Verdier, M., Gibeon, D., Gomez, Cristina, Gove, Kerry, Gozzard, Neil, Guillmant-Farry, E., Henriksson, E., Hewitt, Lorraine, Hoda, U., Hu, Richard, Hu, Sile, Hu, X., Jeyasingham, E., Johnson, K., Jullian, N., Kamphuis, Juliette, Kennington, Erika J., Kerry, Dyson, Kerry, G., Klüglich, M., Knobel, Hugo, Kolmert, Johan, Konradsen, J.R., Kots, Maxim, Kretsos, Kosmas, Krueger, L., Kuo, Scott, Kupczyk, Maciej, Lambrecht, Bart, Lantz, A.-S., Larminie, Christopher, Larsson, L.X., Latzin, P., Lazarinis, N., Lemonnier, N., Lone-Latif, Saeeda, Lowe, L.A., Manta, Alexander, Marouzet, Lisa, Martin, Jane, Mathon, Caroline, McEvoy, L., Meah, Sally, Menzies-Gow, A., Metcalf, Leanne, Mikus, Maria, Monk, Philip, Naz, Shama, Nething, K., Nicholas, Ben, Nihlén, U., Nilsson, Peter, Niven, R., Nordlund, B., Nsubuga, S., Pacino, Antonio, Palkonen, Susanna, Pellet, J., Pennazza, Giorgio, Petrén, Anne, Pink, Sandy, Pison, C., Postle, Anthony, Rahman-Amin, Malayka, Ravanetti, Lara, Ray, Emma, Reinke, Stacey, Reynolds, Leanne, Riemann, K., Robberechts, Martine, Rocha, J.P., Rossios, C., Russell, Kirsty, Rutgers, Michael, Santini, G., Santoninco, Marco, Saqi, M., Schoelch, Corinna, Schofield, James P.R., Scott, S., Sehgal, N., Sjödin, Marcus, Smids, Barbara, Smith, Caroline, Smith, Jessica, Smith, Katherine M., Söderman, P., Sogbessan, A., Spycher, F., Staykova, Doroteya, Stephan, S., Stokholm, J., Strandberg, K., Sunther, M., Szentkereszty, M., Tamasi, L., Tariq, K., Thörngren, John-Olof, Thorsen, Jonathan, Valente, S., van de Pol, Marianne, van Drunen, C.M., Van Eyll, Jonathan, Versnel, Jenny, Vink, Anton, von Garnier, C., Vyas, A., Wald, Frans, Walker, Samantha, Ward, Jonathan, Wetzel, Kristiane, Wiegman, Coen, Williams, Siân, Yang, Xian, Yeyasingham, Elizabeth, Amgen, W. Yu, Zetterquist, W., Zolkipli, Z., Zwinderman, A.H., Östling, Jörgen, van Geest, Marleen, Jevnikar, Zala, Wilson, Susan, Lutter, Rene, Shaw, Dominick E., Bakke, Per S., Caruso, Massimo, Dahlen, Sven-Erik, Fowler, Stephen J., Horváth, Ildikó, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandström, Thomas, Sun, Kai, Pandis, Ioannis, Auffray, Charles, Sousa, Ana R., Guo, Yike, Adcock, Ian M., Howarth, Peter, Chung, Kian Fan, Bigler, Jeanette, Sterk, Peter J., Skipp, Paul J., Djukanović, Ratko, and Vaarala, Outi

Published
2019
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4. Stratification of asthma phenotypes by airway proteomic signatures

Author

Ahmed, H., Allen, D., Badorrek, P., Ballereau, S., Baribaud, F., Bedding, A., Behndig, A.F., Berglind, A., Berton, A., Bigler, J., Boedigheimer, M.J., Bønnelykke, K., Brinkman, P., Bush, A., Campagna, D., Casaulta, C., Chaiboonchoe, A., Davison, T., De Meulder, B., Delin, I., Dennison, P., Dodson, P., El Hadjam, L., Erzen, D., Faulenbach, C., Fichtner, K., Fitch, N., Formaggio, E., Gahlemann, M., Galffy, G., Garissi, D., Garret, T., Gent, J., Guillmant-Farry, E., Henriksson, E., Hoda, U., Hohlfeld, J.M., Hu, X., James, A., Johnson, K., Jullian, N., Kerry, G., Klüglich, M., Knowles, R., Konradsen, J.R., Kretsos, K., Krueger, L., Lantz, A.-S., Larminie, C., Latzin, P., Lefaudeux, D., Lemonnier, N., Lowe, L.A., Lutter, R., Manta, A., Mazein, A., McEvoy, L., Menzies-Gow, A., Mores, N., Murray, C.S., Nething, K., Nihlén, U., Niven, R., Nordlund, B., Nsubuga, S., Pellet, J., Pison, C., Praticò, G., Valls, M. Puig, Riemann, K., Rocha, J.P., Rossios, C., Santini, G., Saqi, M., Scott, S., Sehgal, N., Selby, A., Söderman, P., Sogbesan, A., Spycher, F., Stephan, S., Stokholm, J., Sunther, M., Szentkereszty, M., Tamasi, L., Tariq, K., Valente, S., van Aalderen, W.M., van Drunen, C.M., Van Eyll, J., Vyas, A., Yu, W., Zetterquist, W., Zolkipli, Z., Zwinderman, A.H., Schofield, James P.R., Burg, Dominic, Nicholas, Ben, Strazzeri, Fabio, Brandsma, Joost, Staykova, Doroteya, Folisi, Caterina, Bansal, Aruna T., Xian, Yang, Guo, Yike, Rowe, Anthony, Corfield, Julie, Wilson, Susan, Ward, Jonathan, Lutter, Rene, Shaw, Dominick E., Bakke, Per S., Caruso, Massimo, Dahlen, Sven-Erik, Fowler, Stephen J., Horváth, Ildikó, Howarth, Peter, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandström, Thomas, Sun, Kai, Pandis, Ioannis, Riley, John, Auffray, Charles, De Meulder, Bertrand, Lefaudeux, Diane, Sousa, Ana R., Adcock, Ian M., Chung, Kian Fan, Sterk, Peter J., Skipp, Paul J., and Djukanović, Ratko

Published
2019
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5. TERC polymorphisms are associated both with susceptibility to colorectal cancer and with longer telomeres

Author

Jones, AM, Beggs, AD, Carvajal-Carmona, L, Farrington, S, Tenesa, A, Walker, M, Howarth, K, Ballereau, S, Hodgson, SV, Zauber, A, Bertagnolli, M, Midgley, R, Campbell, H, Kerr, D, Dunlop, MG, and Tomlinson, IPM

Subjects
Prevention, Cancer, Aging, Genetics, Colo-Rectal Cancer, Digestive Diseases, 2.1 Biological and endogenous factors, Aetiology, Adenoma, Aged, Carcinoma, Case-Control Studies, Colorectal Neoplasms, Female, Genetic Predisposition to Disease, Genotyping Techniques, HCT116 Cells, Humans, Leukocytes, Male, Middle Aged, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, RNA, Retrospective Studies, Telomerase, Telomere, Clinical Sciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology
Abstract

Background and aimsShorter telomeres have been associated with increased risk of malignancy, including colorectal cancer (CRC). Telomere length is heritable and may be an intermediate phenotype linked to genetic susceptibility to CRC.MethodsIn a large sample, the study investigated whether candidate single nucleotide polymorphisms (SNP) in 'telomere biology' genes were associated with telomere length in leucocytes. SNP associated with an increased risk of CRC were searched for separately.ResultsCarriers of the common allele at SNP rs10936599, near the telomerase RNA component (TERC) locus, had significantly longer telomeres. It was independently found that the same rs10936599 allele was associated with increased risk of both CRC and colorectal adenomas. Neither telomere length nor CRC risk was associated with variation near telomerase reverse transcriptase or other telomere biology genes. In silico analysis showed that SNP rs2293607 was strongly correlated with rs10936599, mapped within TERC transcripts, had a predicted effect on messenger RNA folding and lay at a reported transcription factor binding site. TERC mRNA were expressed, differing only at the alleles of rs2293607, in CRC cell line HCT116. The long-telomere/CRC-risk allele was associated with higher levels of TERC mRNA and the formation of longer telomeres.ConclusionsCommon genetic variation at TERC is associated with both longer telomeres and an increased risk of CRC, a potential mechanism being reduced levels of cell senescence or death. This finding is somewhat paradoxical, given retrospective studies reporting that CRC cases have shorter telomeres than controls. One possibility is that that association actually results from poorer survival in patients with longer telomeres.

Published
2012

6. Predictors and associations of the persistent airflow limitation phenotype in asthma: a post-hoc analysis of the ATLANTIS study

Author

Kole, Tessa M, primary, Vanden Berghe, Elise, additional, Kraft, Monica, additional, Vonk, Judith M, additional, Nawijn, Martijn C, additional, Siddiqui, Salman, additional, Sun, Kai, additional, Fabbri, Leonardo M, additional, Rabe, Klaus F, additional, Chung, Kian Fan, additional, Nicolini, Gabriele, additional, Papi, Alberto, additional, Brightling, Chris, additional, Singh, Dave, additional, van der Molen, Thys, additional, Dahlén, Sven-Erik, additional, Agusti, Alvar, additional, Faner, Rosa, additional, Wedzicha, Jadwiga A, additional, Donaldson, Gavin C, additional, Adcock, Ian M, additional, Lahousse, Lies, additional, Kerstjens, Huib A M, additional, van den Berge, Maarten, additional, Badorrek, P., additional, Broeders, M., additional, Boersma, W.G., additional, Chetta, A., additional, Cukier, A., additional, D'Amato, M., additional, Djukanovic, R., additional, Foschino, M.P., additional, Gessner, C., additional, Hanania, N., additional, Martin, R., additional, Milleri, S., additional, Olivenstein, R., additional, Paggiaro, P., additional, Pizzichini, E., additional, Plaza Moral, V., additional, Postma, D.S., additional, Scichilone, N., additional, Schilz, R., additional, Spanevello, A., additional, Stelmach, R., additional, Vroegop, J.S., additional, Usmani, O.S., additional, Zhang, Q., additional, Ahmed, H., additional, Allen, D., additional, Ballereau, S., additional, Batuwitage, M.K., additional, Bedding, A., additional, Behndig, A.F., additional, Berglind, A., additional, Berton, A., additional, Bigler, J., additional, Boedigheimer, M.J., additional, Bønnelykke, K., additional, Brinkman, P., additional, Bush, A., additional, Campagna, D., additional, Casaulta, C., additional, Chaiboonchoe, A., additional, Davison, T., additional, De Meulder, B., additional, Delin, I., additional, Dennison, P., additional, Dodson, P., additional, El Hadjam, L., additional, Erzen, D., additional, Faulenbach, C., additional, Fichtner, K., additional, Fitch, N., additional, Formaggio, E., additional, Gahlemann, M., additional, Galffy, G., additional, Garissi, D., additional, Garret, T., additional, Guillmant-Farry, E., additional, Henriksson, E., additional, Hoda, U., additional, Hohlfeld, J.M., additional, Hu, X., additional, James, A., additional, Johnson, K., additional, Jullian, N., additional, Kerry, G., additional, Klüglich, M., additional, Knowles, R., additional, Konradsen, J.R., additional, Kretsos, K., additional, Krueger, L., additional, Lantz, A-S., additional, Larminie, C., additional, Latzin, P., additional, Lefaudeux, D., additional, Lemonnier, N., additional, Lowe, L.A., additional, Lutter, R., additional, Manta, A., additional, Mazein, A., additional, McEvoy, L., additional, Menzies-Gow, A., additional, Mores, N., additional, Murray, C.S., additional, Nething, K., additional, Nihlén, U., additional, Niven, R., additional, Nordlund, B., additional, Nsubuga, S., additional, Pellet, J., additional, Pison, C., additional, Praticò, G., additional, Puig Valls, M., additional, Riemann, K., additional, Rocha, J.P., additional, Rossios, C., additional, Santini, G., additional, Sagi, M., additional, Scott, S., additional, Sehgal, N., additional, Selby, A., additional, Söderman, P., additional, Sogbesan, A., additional, Spycher, F., additional, Stephan, S., additional, Stokholm, J., additional, Sunther, M., additional, Szentkereszty, M., additional, Tamasi, L., additional, Tariq, K., additional, Valente, S, additional, Van Aalderen, W.M., additional, Van Drunen, C.M., additional, Van Eyll, J., additional, Vyas, A., additional, Yu, W., additional, Zetterguist, W., additional, Zolkipli, Z., additional, Zwinderman, A.H., additional, Agusti, A., additional, Wedzicha, J.A., additional, Donaldson, G.C., additional, Faner, R., additional, Breyer-Kohansal, R., additional, Maitland-van der Zee, A.H., additional, Melén, E., additional, Allinson, J.P., additional, Vanfleteren, L.E.G.W., additional, Vestbo, J., additional, Adcock, I.M., additional, Lahousse, L., additional, Van den Berge, M., additional, Alter, P., additional, Barbe, F., additional, Brightling, C.E., additional, Breyer, M.K., additional, Burghuber, O.C., additional, Casas, M., additional, Chung, K.F., additional, Cosío, B.G., additional, Crispi, F., additional, De Batlle, J., additional, Fitting, J.W., additional, Garcia, J., additional, Hallberg, J., additional, Hartl, S., additional, Jarvis, D., additional, Mathioudakis, A., additional, Nicod, L., additional, Papi, A., additional, Ritchie, A., additional, Sigsgaard, T., additional, Sterk, P.J., additional, Ullman, A., additional, Vellvé, K., additional, Vogelmeier, C., additional, Wheelock, A.M., additional, and Wheelock, C.E., additional

Published
2023
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8. Are allergic multimorbidities and IgE polysensitization associated with the persistence or re-occurrence of foetal type 2 signalling? The MeDALL hypothesis

Author

Bousquet, J., Anto, J. M., Wickman, M., Keil, T., Valenta, R., Haahtela, T., Lodrup Carlsen, K., van Hage, M., Akdis, C., Bachert, C., Akdis, M., Auffray, C., Annesi-Maesano, I., Bindslev-Jensen, C., Cambon-Thomsen, A., Carlsen, K. H., Chatzi, L., Forastiere, F., Garcia-Aymerich, J., Gehrig, U., Guerra, S., Heinrich, J., Koppelman, G. H., Kowalski, M. L., Lambrecht, B., Lupinek, C., Maier, D., Melén, E., Momas, I., Palkonen, S., Pinart, M., Postma, D., Siroux, V., Smit, H. A., Sunyer, J., Wright, J., Zuberbier, T., Arshad, S. H., Nadif, R., Thijs, C., Andersson, N., Asarnoj, A., Ballardini, N., Ballereau, S., Bedbrook, A., Benet, M., Bergstrom, A., Brunekreef, B., Burte, E., Calderon, M., De Carlo, G., Demoly, P., Eller, E., Fantini, M. P., Hammad, H., Hohman, C., Just, J., Kerkhof, M., Kogevinas, M., Kull, I., Lau, S., Lemonnier, N., Mommers, M., Nawijn, M., Neubauer, A., Oddie, S., Pellet, J., Pin, I., Porta, D., Saes, Y., Skrindo, I., Tischer, C. G., Torrent, M., and von Hertzen, L.

Published
2015
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9. COVID-19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms (vol 17, e10387, 2021)

Author

Ostaszewski, M, Niarakis, A, Mazein, A, Kuperstein, I, Phair, R, Orta-Resendiz, A, Singh, V, Aghamiri, S, Acencio, M, Glaab, E, Ruepp, A, Fobo, G, Montrone, C, Brauner, B, Frishman, G, Gomez, L, Somers, J, Hoch, M, Gupta, S, Scheel, J, Borlinghaus, H, Czauderna, T, Schreiber, F, Montagud, A, de Leon, M, Funahashi, A, Hiki, Y, Hiroi, N, Yamada, T, Drager, A, Renz, A, Naveez, M, Bocskei, Z, Messina, F, Bornigen, D, Fergusson, L, Conti, M, Rameil, M, Nakonecnij, V, Vanhoefer, J, Schmiester, L, Wang, M, Ackerman, E, Shoemaker, J, Zucker, J, Oxford, K, Teuton, J, Kocakaya, E, Summak, G, Hanspers, K, Kutmon, M, Coort, S, Eijssen, L, Ehrhart, F, Rex, D, Slenter, D, Martens, M, Pham, N, Haw, R, Jassal, B, Matthews, L, Orlic-Milacic, M, Senff-Ribeiro, A, Rothfels, K, Shamovsky, V, Stephan, R, Sevilla, C, Varusai, T, Ravel, J, Fraser, R, Ortseifen, V, Marchesi, S, Gawron, P, Smula, E, Heirendt, L, Satagopam, V, Gm, W, Riutta, A, Golebiewski, M, Owen, S, Goble, C, Xm, H, Overall, R, Maier, D, Bauch, A, Gyori, B, Bachman, J, Vega, C, Groues, V, Vazquez, M, Porras, P, Licata, L, Iannuccelli, M, Sacco, F, Nesterova, A, Yuryev, A, de Waard, A, Turei, D, Luna, A, Babur, O, Soliman, S, Valdeolivas, A, Esteban-Medina, M, Pena-Chilet, M, Rian, K, Helikar, T, Puniya, B, Modos, D, Treveil, A, Olbei, M, De Meulder, B, Ballereau, S, Dugourd, A, Naldi, A, Noel, V, Calzone, L, Sander, C, Demir, E, Korcsmaros, T, Freeman, T, Auge, F, Beckmann, J, Hasenauer, J, Wolkenhauer, O, Willighagen, E, Pico, A, Evelo, C, Gillespie, M, Stein, L, Hermjakob, H, D'Eustachio, P, Saez-Rodriguez, J, Dopazo, J, Valencia, A, Kitano, H, Barillot, E, Auffray, C, Balling, R, and Schneider, R

Subjects
Settore BIO/18, Settore BIO/11
Published
2021

10. Stratification of asthma phenotypes by airway proteomic signatures

Author

Schofield, James P. R., Burg, Dominic, Nicholas, Ben, Strazzeri, Fabio, Brandsma, Joost, Staykova, Doroteya, Folisi, Caterina, Bansal, Aruna T., Xian, Yang, Guo, Yike, Rowe, Anthony, Corfield, Julie, Wilson, Susan, Ward, Jonathan, Lutter, Rene, Shaw, Dominick E., Bakke, Per S., Caruso, Massimo, Dahlen, Sven-Erik, Fowler, Stephen J., Horvath, Ildiko, Howarth, Peter, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandstrom, Thomas, Sun, Kai, Pandis, Ioannis, Riley, John, Auffray, Charles, De Meulder, Bertrand, Lefaudeux, Diane, Sousa, Ana R., Adcock, Ian M., Chung, Kian Fan, Sterk, Peter J., Skipp, Paul J., Djukanovic, Ratko, Ahmed, H., Allen, D., Badorrek, P., Ballereau, S., Baribaud, F., Batuwitage, M. K., Bedding, A., Behndig, A. F., Berglind, A., Berton, A., Bigler, J., Boedigheimer, M. J., Bonnelykke, K., Brinkman, P., Bush, A., Campagna, D., Casaulta, C., Chaiboonchoe, A., Davison, T., De Meulder, B., Delin, I., Dennison, P., Dodson, P., El Hadjam, L., Erzen, D., Faulenbach, C., Fichtner, K., Fitch, N., Formaggio, E., Gahlemann, M., Galffy, G., Garissi, D., Garret, T., Gent, J., Guillmant-Farry, E., Henriksson, E., Hoda, U., Hohlfeld, J. M., Hu, X., James, A., Johnson, K., Jullian, N., Kerry, G., Klueglich, M., Knowles, R., Konradsen, J. R., Kretsos, K., Krueger, L., Lantz, A. -S, Larminie, C., Latzin, P., Lefaudeux, D., Lemonnier, N., Lowe, L. A., Lutter, R., Manta, A., Mazein, A., McEvoy, L., Menzies-Gow, A., Mores, N., Murray, C. S., Nething, K., Nihlen, U., Niven, R., Nordlund, B., Nsubuga, S., Pellet, J., Pison, C., Pratico, G., Puig Valls, M., Riemann, K., Rocha, J. P., Rossios, C., Santini, G., Saqi, M., Scott, S., Sehgal, N., Selby, A., Soderman, P., Sogbesan, A., Spycher, F., Stephan, S., Stokholm, J., Sunther, M., Szentkereszty, M., Tamasi, L., Tariq, K., Valente, S., van Aalderen, W. M., van Drunen, C. M., Van Eyll, J., Vyas, A., Yu, W., Zetterquist, W., Zolkipli, Z., Zwinderman, A. H., Adriaens, Nora, Aliprantis, Antonios, Alving, Kjell, Bakke, Per, Balgoma, David, Barber, Clair, Baribaud, Frederic, Bates, Stewart, Bautmans, An, Beleta, Jorge, Bochenek, Grazyna, Braun, Armin, Carayannopoulos, Leon, Rocha, Joao Pedro Carvalho da Purificacao, Chaleckis, Romanas, D'Amico, Arnaldo, De Alba, Jorge, De Lepeleire, Inge, Dekker, Tamara, Dijkhuis, Annemiek, Draper, Aleksandra, Edwards, Jessica, Emma, Rosalia, Ericsson, Magnus, Flood, Breda, Gallart, Hector, Gomez, Cristina, Gove, Kerry, Gozzard, Neil, Haughney, John, Hewitt, Lorraine, Hohlfeld, Jens, Holweg, Cecile, Hu, Richard, Hu, Sile, Kamphuis, Juliette, Kennington, Erika J., Kerry, Dyson, Knobel, Hugo, Kolmert, Johan, Kots, Maxim, Kuo, Scott, Kupczyk, Maciej, Lambrecht, Bart, Lone-Latif, Saeeda, Loza, Matthew J., Marouzet, Lisa, Martin, Jane, Masefield, Sarah, Mathon, Caroline, Meah, Sally, Meiser, Andrea, Metcalf, Leanne, Mikus, Maria, Miralpeix, Montse, Monk, Philip, Naz, Shama, Nilsson, Peter, Ostling, Jorgen, Pacino, Antonio, Palkonen, Susanna, Pavlidis, Stelios, Pennazza, Giorgio, Petren, Anne, Pink, Sandy, Postle, Anthony, Powell, Pippa, Rahman-Amin, Malayka, Rao, Navin, Ravanetti, Lara, Ray, Emma, Reinke, Stacey, Reynolds, Leanne, Robberechts, Martine, Roberts, Amanda, Russell, Kirsty, Rutgers, Michael, Santoninco, Marco, Schoelch, Corinna, Sjodin, Marcus, Smids, Barbara, Smith, Caroline, Smith, Jessica, Smith, Katherine M., Thorngren, John-Olof, Thornton, Bob, Thorsen, Jonathan, van de Pol, Marianne, van Geest, Marleen, Versnel, Jenny, Vink, Anton, Wald, Frans, Walker, Samantha, Weiszhart, Zsoka, Wetzel, Kristiane, Wheelock, Craig E., Wiegman, Coen, Williams, Sian, Wilson, Susan J., Woodcock, Ashley, Yang, Xian, Yeyasingham, Elizabeth, Prins, Jan-Bas, Gahlemann, Martina, Visintin, Luigi, Evans, Hazel, Puhl, Martine, Buzermaniene, Lina, Hudson, Val, Bond, Laura, de Boer, Pim, Widdershoven, Guy, Sigmund, Ralf, Supple, David, Hamerlijnck, Dominique, Negus, Jenny, Kamphuis, Julitte, Sergison, Lehanne, Onstein, Susanne, MacNee, William, Bernardini, Renato, Bont, Louis, Wecksell, Per-Ake, Graduate School, AII - Inflammatory diseases, Pulmonology, Ear, Nose and Throat, Epidemiology and Data Science, APH - Methodology, Publica, and Commission of the European Communities

Subjects
0301 basic medicine, Male, Proteomics, Allergy, Proteome, Neutrophils, Respiratory Medicine and Allergy, Transcriptome, 0302 clinical medicine, neutrophils, Forced Expiratory Volume, Immunology and Allergy, CD44, 610 Medicine & health, Lungmedicin och allergi, phenotypes, Middle Aged, medicine.anatomical_structure, Phenotype, 1107 Immunology, Female, eosinophils, medicine.symptom, Life Sciences & Biomedicine, Adult, Settore BIO/14 - FARMACOLOGIA, Immunology, Computational biology, 03 medical and health sciences, Young Adult, proteomics, Eosinophilia, medicine, Humans, U-BIOPRED Study Group, Asthma, Aged, Science & Technology, Microarray analysis techniques, business.industry, Sputum, biomarkers, DEGRADATION, Eosinophil, medicine.disease, Eosinophils, EXACERBATIONS, 030104 developmental biology, 030228 respiratory system, business
Abstract

Background: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy in prediction of treatment responses and a need for better understanding of the underlying mechanisms. Objective: We sought to identify molecular subphenotypes of asthma defined by proteomic signatures for improved stratification. Methods: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyze the proteomes of sputum supernatants from 246 participants (206 asthmatic patients) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms. Results: Analysis of the sputum proteome resulted in 10 clusters (ie, proteotypes) based on similarity in proteomic features, representing discrete molecular subphenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined 3 of these as highly eosinophilic, 3 as highly neutrophilic, and 2 as highly atopic with relatively low granulocytic inflammation. For each of these 3 phenotypes, logistic regression analysis identified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms. Conclusion: This study provides further stratification of asthma currently classified based on quantification of granulocytic inflammation and provided additional insight into their underlying mechanisms, which could become targets for novel therapies. asthma proteomics biomarkers eosinophils neutrophils

Published
2019

11. Epithelial dysregulation in obese severe asthmatics with gastro-oesophageal reflux

Author

Perotin, Jeanne-Marie, Schofield, James PR, Wilson, Susan J, Ward, Jonathan, Brandsma, Joost, Strazzeri, Fabio, Bansal, Aruna, Yang, Xian, Rowe, Anthony, Corfield, Julie, Lutter, Rene, Shaw, Dominick E, Bakke, Per S, Caruso, Massimo, Dahlen, Barbro, Fowler, Stephen J, Horvath, Ildiko, Howarth, Peter, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandstrom, Thomas, Sun, Kai, Pandis, Ioannis, Auffray, Charles, De Meulder, Bertrand, Lefaudeux, Diane, Riley, John H, Sousa, Ana R, Dahlen, Sven-Erik, Adcock, Ian M, Chung, Kian Fan, Sterk, Peter J, Skipp, Paul J, Collins, Jane E, Davies, Donna E, Djukanovic, Ratko, Adcock, IM, Ahmed, H, Auffray, C, Bakke, P, Banssal, AT, Baribaud, F, Bates, S, Bel, EH, Bigler, J, Bisgaard, H, Boedigheimer, MJ, Bonnelykke, K, Brandsma, J, Brinkman, P, Bucchioni, E, Burg, D, Bush, A, Caruso, M, Chaiboonchoe, A, Chanez, P, Chung, KF, Compton, CH, Corfield, J, D'Amico, A, Dahlen, SE, De Meulder, B, Djukanovic, R, Erpenbeck, VJ, Erzen, D, Fichtner, K, Fitch, N, Fleming, LJ, Formaggio, E, Fowler, SJ, Frey, U, Gahlemann, M, Geiser, T, Guo, Y, Hashimoto, S, Haughney, J, Hedlin, G, Hekking, PW, Higenbottam, T, Hohlfeld, JM, Holweg, C, Horvath, I, Howarth, P, James, AJ, Knowles, R, Knox, AJ, Krug, N, Lefaudeux, D, Loza, MJ, Lutter, R, Manta, A, Masefield, S, Matthews, JG, Mazein, A, Meiser, A, Middelveld, RJM, Miralpeix, M, Montuschi, P, Mores, N, Murray, CS, Musial, J, Myles, D, Pahus, L, Pandis, I, Pavlidis, S, Powell, P, Pratico, G, Puig Valls, M, Rao, N, Riley, J, Roberts, A, Roberts, G., Rowe, A, Sandstrom, T, Seibold, W, Selby, A, Shaw, DE, Sigmund, R, Singer, F, Skipp, PJ, Sousa, AR, Sterk, PJ, Sun, K, Thornton, B, van Aalderen, WM, van Geest, M, Vestbo, J, Vissing, NH, Wagener, AH, Wagers, SS, Weiszhart, Z, Wheelock, CE, Wilson, SJ, Aliprantis, Antonios, Allen, David, Alving, Kjell, Badorrek, P, Balgoma, David, Ballereau, S, Barber, Clair, Batuwitage, Manohara Kanangana, Bautmans, An, Bedding, A, Behndig, AF, Beleta, Jorge, Berglind, A, Berton, A, Bochenek, G, Braun, A, Campagna, D, Carayannopoulos, L, Casaulta, C, Chaleckis, Romanas, Dahlen, B, Davison, T, De Alba, J, De Lepeleire, I, Dekker, T, Delin, I, Dennison, P, Dijkhuis, A, Dodson, P, Dyson, K, Edwards, J, El Hadjam, L, Emma, R, Ericsson, M, Faulenbach, C, Flood, Breda, Galffy, G, Gallart, H, Garissi, D, Gent, J., Gerhardsson de Verdier, M, Gibeon, D, Gomez, Cristina, Gove, K, Guillmant-Farry, E, Henriksson, E, Hewitt, L, Hoda, U, Hu, Richard, Hu, S, Hu, X, Jeyasingham, E, Johnson, K, Jullian, N, Kamphuis, J, Kennington, EJ, Kerry, D, Kerry, G, Klueglich, M, Knobel, H, Kolmert, Johan, Konradsen, JR, Kots, M, Kretsos, Kosmas, Krueger, L, Kuo, S, Kupczyk, M, Lambrecht, Bart, Lantz, A-S, Larminie, Christopher, Larsson, LX, Latzin, P, Lazarinis, N, Lemonnier, N, Lone-Latif, S, Lowe, LA, Marouzet, L, Martin, J, Mathon, C, McEvoy, L, Meah, S, Menzies-Gow, A, Metcalf, L, Mikus, M, Monk, P, Naz, S, Nething, K, Nicholas, B, Nihlen, U, Nilsson, Peter, Niven, R, Nordlund, B, Nsubuga, S, Ostling, J, Pacino, A, Palkonen, S, Pellet, J, Pennazza, G, Petren, A, Pink, S, Pison, C, Postle, A, Rahman-Amin, M, Ravanetti, L, Ray, E, Reinke, S, Reynolds, L, Riemann, K, Robberechts, Martine, Rocha, JP, Rossios, C, Russell, K, Rutgers, M, Santini, G, Santoninco, M, Saqi, M, Schoelch, C, Schofield, JPR, Scott, S, Sehgal, N, Sjodin, M, Smids, B, Smith, Caroline, Smith, J, Smith, KM, Soderman, P, Sogbessan, A, Spycher, F, Staykova, D, Stephan, S, Stokholm, J, Strandberg, K, Sunther, M, Szentkereszty, M, Tamasi, L, Tariq, K, Thorngren, J-O, Thorsen, Jonathan, Valente, S, van de Pol, Marianne, van Drunen, CM, Van Eyll, J, Versnel, J, Vink, A, von Garnier, C, Vyas, A, Wald, F, Walker, S, Ward, J, Wetzel, K, Wiegman, C, Williams, S, Yang, X, Yeyasingham, E, Yu, W, Zetterquist, W, Zolkipli, Z, Zwinderman, AH, Prins, J-B, Visintin, L, Evans, H, Puhl, M, Buzermaniene, L, Hudson, V, Bond, L, de Boer, P, Widdershoven, G, Supple, D, Hamerlijnck, D, Negus, J, Sergison, L, Onstein, S, MacNee, W, Bernardini, R, Bont, Louis, Wecksell, P-A, Draper, Aleksandra, Gozzard, Neil, Commission of the European Communities, Publica, Pulmonology, AII - Inflammatory diseases, Ear, Nose and Throat, Epidemiology and Data Science, APH - Methodology, and NIHR Southampton Biomedical Research Centre

Subjects
severe asthma, Pulmonary and Respiratory Medicine, endotyping, Gastrointestinal, phenotyping, Settore BIO/14 - FARMACOLOGIA, [SDV]Life Sciences [q-bio], Respiratory System, ROWE, Gene Expression, Article, Endoscopy, Gastrointestinal, Epithelium, CCN Intercellular Signaling Proteins, Patent application, 03 medical and health sciences, 0302 clinical medicine, Shareholder, gatroesophageal reflux, Nothing, Proto-Oncogene Proteins, Medicine and Health Sciences, Humans, Medicine, Obesity, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, 11 Medical and Health Sciences, U-BIOPRED Study Group, Science & Technology, business.industry, U-BIOPRED, digestive, oral, and skin physiology, Airway inflammation, Conflict of interest, Biology and Life Sciences, Endoscopy, Asthma, digestive system diseases, 3. Good health, 030228 respiratory system, Spin out, Case-Control Studies, Law, Honorarium, Gastroesophageal Reflux, business, Life Sciences & Biomedicine
Abstract

Gastro-oesophageal reflux disease (GORD) and obesity are associated with frequent exacerbations and poor quality of life in asthmatics. Multiple mechanisms have been proposed for the effect of obesity, including modification of inflammation affecting epithelial cell proliferation and wound repair, while the role of GORD is poorly understood and proton pump inhibitor (PPI) are of variable efficacy. GORD might exert a deleterious effect by inducing vagal reflex, neuroinflammation and directly ( via microaspiration) triggering airway inflammation. Studies of reflux in animal models and human bronchial epithelial cell culture show varying impact on inflammation and airway remodelling. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr PEROTIN has nothing to disclose. Conflict of interest: Dr Schofield has nothing to disclose. Conflict of interest: Dr Wilson has nothing to disclose. Conflict of interest: Dr Ward has nothing to disclose. Conflict of interest: Dr Brandsma has nothing to disclose. Conflict of interest: Dr Strazzeri has nothing to disclose. Conflict of interest: Dr Bansal has nothing to disclose. Conflict of interest: Dr Yang has nothing to disclose. Conflict of interest: Dr Rowe reports and a full time employee and shareholder of Janssen Pharmaceutical Companies of Johnson and Johnson. Conflict of interest: Miss Corfield has nothing to disclose. Conflict of interest: Dr Lutter has nothing to disclose. Conflict of interest: Prof. Shaw reports personal fees and non-financial support from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Novartis, personal fees from Teva, personal fees from Circassia, and a grant from GSK, outside the submitted work. Conflict of interest: Dr Bakke reports personal fees from GSK, AZ, Novartis andTeva, outside the submitted work. Conflict of interest: MC have no conflict of interest to disclose. Conflict of interest: Dr Dahlen has nothing to disclose. Conflict of interest: Dr Fowler reports personal fees and non-financial support from AstraZeneca, grants and personal fees from Boehringer Ingelheim, personal fees from Novartis, personal fees from Teva, outside the submitted work. Conflict of interest: Dr Horvath reports personal fees from Astra Zeneca, Boehringer Ingelheim, Novartis, CSL, Chiesi, Roche, GSK, Berlin-Chemie and Sandoz, outside the submitted work. Conflict of interest: Dr Howarth reports personal fees from GSK, outside the submitted work. Conflict of interest: Dr Krug has nothing to disclose. Conflict of interest: Dr Montuschi has nothing to disclose. Conflict of interest: Dr Sanak has nothing to disclose. Conflict of interest: Dr Sandstrom reports other monetary support from Boehringer Ingelheim, outside the submitted work. Conflict of interest: Dr Sun has nothing to disclose. Conflict of interest: Dr Pandis has nothing to disclose. Conflict of interest: Dr Auffray reports grants from Innovative Medicine Initiative, during the conduct of the study. Conflict of interest: Dr De Meulder reports grants from Innovative Medicine Initiative, during the conduct of the study. Conflict of interest: Ms. Lefaudeux reports grants from Innovative Medicine Initiative, grants from Innovative Medicine Initiative, during the conduct of the study. Conflict of interest: Dr Riley reports and I have shares in and I am employed by GSK. Conflict of interest: Dr Sousa has nothing to disclose. Conflict of interest: Dr Dahlen has nothing to disclose. Conflict of interest: Dr Adcock reports grants from EU-IMI, during the conduct of the study. Conflict of interest: KFC has received honoraria for participating in Advisory Board meetings of GSK, AZ, BI, Teva, Novartis and Merck regarding treatments for asthma and chronic obstructive pulmonary disease and has also been renumerated for speaking engagements. Conflict of interest: Dr Sterk reports grants from Innovative Medicines Initiative, during the conduct of the study. Conflict of interest: Dr Skipp has nothing to disclose. Conflict of interest: Dr Collins reports a patent application for use of a genetically modified Drosophila line carrying one or more mammalian genes associated with a chronic respiratory disease and uses to screen the impact of such genes. Conflict of interest: Dr Davies has nothing to disclose. Conflict of interest: Dr Djukanovic reports receiving fees for lectures at symposia organised by Novartis, AstraZeneca and TEVA, consultation for TEVA and Novartis as member of advisory boards, and participation in a scientific discussion about asthma organised by GlaxoSmithKline. He is a co-founder and current consultant, and has shares in Synairgen, a University of Southampton spin out company.

Published
2019

13. A computational framework for complex disease stratification from multiple large-scale datasets

Author

De Meulder, B., Lefaudeux, D., Bansal, A. T., Mazein, A., Chaiboonchoe, A., Ahmed, H., Balaur, I., Saqi, M., Pellet, J., Ballereau, S., Lemonnier, N., Sun, K., Pandis, I., Yang, X., Batuwitage, M., Kretsos, K., van Eyll, J., Bedding, A., Davison, T., Dodson, P., Larminie, C., Postle, A., Corfield, J., Djukanovic, R., Chung, K. F., Adcock, I. M., Guo, Y. -K., Sterk, P. J., Manta, A., Rowe, A., Baribaud, F., Auffray, C., Gibeon, D., Hoda, U., Kuo, S., Meah, S., Meiser, A., Fleming, L. J., Hu, S., Pavlidis, S., Rossios, C., Russel, K., Wiegman, C., Nezhad, A. T., Oehmichen, A., O'Malley, D., Guitton, F., Emam, I., Agapow, P., Rice, P., Miles, S., Elyasigomari, V., Bel, E., Brinkman, P., Dekker, T., Dijkhuis, A., Hashimoto, S., Hekking, P. -P., Lone-Latif, S., Lutter, R., Ravanetti, L., Smids, B., van Aalderen, W., van de Pol, M., van Drunen, K., van Drunen, M., Wagener, A., Zwinderman, K., Adriaens, N., Carusi, A. M., Richard, F., Nogueira, M. M., Taibi, N., Brasier, O., Aliprantis, A., Alving, K., Faulenbach, C., Braun, A., Hohlfeld, J., Krug, N., Badorrek, P., Bakke, P., Berglind, A., Chaleckis, R., Dahlen, B., Delin, I., Gallart, H., Gomez, C., Hedlin, G., Henriksson, E., James, A. J., Kolmert, J., Konradsen, J., Kupczyk, M., Lantz, A. -S., Lazarinis, L., Mathon, C., Middelveld, R., Naz, S., Nordlund, B., Petren, A., Reinke, S., Sjodin, M., Soderman, P., Strandberg, K., Wheelock, C. E., Zetterquist, W., Balgoma, D., Brandsma, J., Burg, D., Dennison, P., Nicholas, B., Schofield, J. P. R., Skipp, P. J., Staykova, D., Tariq, K., Ward, J., Wilson, S. J., Barber, C., Loza, M. J., Bautmans, A., Sandstrom, T., Behndig, A. F., De Alba, J., Beleta, J., Berton, A., de Verdier, M. G., Nihlen, U., Ostling, J., Dalentoft, T., Lindgren, E., Boedigheimer, M. J., Hu, R., Hu, X., Yu, W., Bigler, J., Bonnelykke, K., Thorsen, J., Vising, N., Bisgaard, H., Bochenek, G., Caruso, M., Emma, R., Campagna, D., Thornton, B., Carayannopoulos, L., Gent, J., Manzies-Gow, A., Sogbesan, A., da Purificacao Rocha, P. C., Pedro, J., Chanez, P., Edwards, J., Flood, B., Hudson, V., Kennington, E. J., Metcalf, L., Rahman-Amin, M., Reynolds, L., Roberts, A., Smith, J., Supple, D., Versnel, J., Walker, S., Coleman, C., Hasan, S., Compton, C., Myles, D., Riley, J., Sousa, A. R., Yeyasingham, E., Pennazza, G., Santoninco, M., D'Amico, A., Dahlen, S. -E., de Boer, P., Robberechts, M., De Lepeleire, I., Fitch, N., Garret, T., Wagers, S., Draper, A., Thorngren, J. -O., Ericsson, M., Erpenbeck, V., Kluglich, M., Nething, K., Riemann, K., Schoelch, C., Seibold, W., Sigmund, R., Wald, F., Wetzel, K., Fichtner, K., Erzen, D., Galffy, G., Horvath, I., Szentkereszty, M., Tamasi, L., Fowler, S. J., Krueger, L., Singer, F., Frey, U., Gahlemann, M., Geiser, T., Hewitt, L., Howarth, P., Marouzet, L., Martin, J., Pink, S., Ray, E., Roberts, G., Smith, C., Gove, K., Gozzard, N., Williams, S., Haughney, J., Higgenbottam, T., Matthews, J. G., Holweg, C., Rutgers, M., Kamphuis, J., Kerry, D., Vink, A., Knobel, H., Knowles, R., Shaw, D. E., Smith, K. M., Know, A., Kots, M., Lambrecht, B., Masefield, S., Nilsson, P., Mikus, M., Miralpeix, M., Monk, P., Mores, N., Valente, S., Montuschi, P., Murray, C. S., Musial, J., Pacino, A., Pahus, L., Palkonen, S., Powel, P., Rao, N., Santini, G., Vestbo, J., von Garnier, C., Weiszhart, Z., Woodcock, A., Biryukov, M., Schneider, R., Herzinger, S., Satagopam, V., Gu, W., da Silva, A. B., Tielmann, A., Bergeron, J., Gaudette, A., Silberberg, A., Henderson, D., Hayat, S., Elefsinioti, A., Moltzen, E. K., Harbo, I. S., Birgitte, J., Bratfalean, D., Houston, P., Kisler, B., Capdevila, F. B., Verbeeck, D., Marchetti, G., Rahal, G., Schuermann, H. D., Mazuranok, L., Hendlich, M., Painell'S, L., Marren, D., Martasek, J., Rimell, J., Romacker, M., Braxenthaler, M., Sansone, S. -A., Rocca-Serra, P., Commission of the European Communities, Pulmonology, Graduate School, Experimental Immunology, Paediatric Pulmonology, Ear, Nose and Throat, Epidemiology and Data Science, APH - Methodology, ARD - Amsterdam Reproduction and Development, Consortium, U-Biopred Study Group And The Etriks, Rocca-Serra, P, Sansone, S, De Meulder, Bertrand [0000-0002-2108-7657], and Apollo - University of Cambridge Repository

Subjects
Quality Control, 0301 basic medicine, Computer science, Bioinformatics, Systems biology, Big data, Environmental data, Machine Learning, Set (abstract data type), 03 medical and health sciences, Structural Biology, Modelling and Simulation, Cluster Analysis, U-BIOPRED Study Group and the eTRIKS Consortium, Disease, False Positive Reactions, Cluster analysis, Molecular signatures, Molecular Biology, lcsh:QH301-705.5, ‘Omics data, 'Omics data, business.industry, Systems Biology, Applied Mathematics, 1199 Other Medical And Health Sciences, Data science, 3. Good health, Computer Science Applications, Systems medicine, 030104 developmental biology, lcsh:Biology (General), Feature (computer vision), Modeling and Simulation, Stratification, Scale (map), business, Biomarkers, Research Article
Abstract

Background Multilevel data integration is becoming a major area of research in systems biology. Within this area, multi-‘omics datasets on complex diseases are becoming more readily available and there is a need to set standards and good practices for integrated analysis of biological, clinical and environmental data. We present a framework to plan and generate single and multi-‘omics signatures of disease states. Methods The framework is divided into four major steps: dataset subsetting, feature filtering, ‘omics-based clustering and biomarker identification. Results We illustrate the usefulness of this framework by identifying potential patient clusters based on integrated multi-‘omics signatures in a publicly available ovarian cystadenocarcinoma dataset. The analysis generated a higher number of stable and clinically relevant clusters than previously reported, and enabled the generation of predictive models of patient outcomes. Conclusions This framework will help health researchers plan and perform multi-‘omics big data analyses to generate hypotheses and make sense of their rich, diverse and ever growing datasets, to enable implementation of translational P4 medicine. Electronic supplementary material The online version of this article (10.1186/s12918-018-0556-z) contains supplementary material, which is available to authorized users.

Published
2018

14. IL-17–high asthma with features of a psoriasis immunophenotype

Author

Östling, Jörgen, primary, van Geest, Marleen, additional, Schofield, James P.R., additional, Jevnikar, Zala, additional, Wilson, Susan, additional, Ward, Jonathan, additional, Lutter, Rene, additional, Shaw, Dominick E., additional, Bakke, Per S., additional, Caruso, Massimo, additional, Dahlen, Sven-Erik, additional, Fowler, Stephen J., additional, Horváth, Ildikó, additional, Krug, Norbert, additional, Montuschi, Paolo, additional, Sanak, Marek, additional, Sandström, Thomas, additional, Sun, Kai, additional, Pandis, Ioannis, additional, Auffray, Charles, additional, Sousa, Ana R., additional, Guo, Yike, additional, Adcock, Ian M., additional, Howarth, Peter, additional, Chung, Kian Fan, additional, Bigler, Jeanette, additional, Sterk, Peter J., additional, Skipp, Paul J., additional, Djukanović, Ratko, additional, Vaarala, Outi, additional, Adcock, I.M., additional, Ahmed, H., additional, Auffray, C., additional, Bakke, P., additional, Bansal, A.T., additional, Baribaud, F., additional, Bates, S., additional, Bel, E.H., additional, Bigler, J., additional, Bisgaard, H., additional, Boedigheimer, M.J., additional, Bønnelykke, K., additional, Brandsma, J., additional, Brinkman, P., additional, Bucchioni, E., additional, Burg, D., additional, Bush, A., additional, Caruso, M., additional, Chaiboonchoe, A., additional, Chanez, P., additional, Chung, K.F., additional, Compton, C.H., additional, Corfield, J., additional, D'Amico, A., additional, Dahlen, S.E., additional, De Meulder, B., additional, Djukanovic, R., additional, Erpenbeck, V.J., additional, Erzen, D., additional, Fichtner, K., additional, Fitch, N., additional, Fleming, L.J., additional, Formaggio, E., additional, Fowler, S.J., additional, Frey, U., additional, Gahlemann, M., additional, Geiser, T., additional, Guo, Y., additional, Hashimoto, S., additional, Haughney, J., additional, Hedlin, G., additional, Hekking, P.W., additional, Higenbottam, T., additional, Hohlfeld, J.M., additional, Holweg, C., additional, Horváth, I., additional, Howarth, P., additional, James, A.J., additional, Knowles, R., additional, Knox, A.J., additional, Krug, N., additional, Lefaudeux, D., additional, Loza, M.J., additional, Lutter, R., additional, Manta, A., additional, Masefield, S., additional, Mazein, A., additional, Meiser, A., additional, Middelveld, R.J.M., additional, Miralpeix, M., additional, Montuschi, P., additional, Mores, N., additional, Murray, C.S., additional, Musial, J., additional, Myles, D., additional, Pahus, L., additional, Pandis, I., additional, Pavlidis, S., additional, Powell, P., additional, Praticò, G., additional, Rao, M. Puig N., additional, Riley, J., additional, Roberts, A., additional, Roberts, G., additional, Rowe, A., additional, Sandström, T., additional, Seibold, W., additional, Selby, A., additional, Shaw, D.E., additional, Sigmund, R., additional, Singer, F., additional, Skipp, P.J., additional, Sousa, A.R., additional, Sterk, P.J., additional, Sun, K., additional, Thornton, B., additional, van Aalderen, W.M., additional, van Geest, M., additional, Vestbo, J., additional, Vissing, N.H., additional, Wagener, A.H., additional, Wagers, S.S., additional, Weiszhart, Z., additional, Wheelock, C.E., additional, Wilson, S.J., additional, Aliprantis, Antonios, additional, Allen, David, additional, Alving, Kjell, additional, Badorrek, P., additional, Balgoma, David, additional, Ballereau, S., additional, Barber, Clair, additional, Batuwitage, Manohara Kanangana, additional, Bautmans, A., additional, Bedding, A., additional, Behndig, A.F., additional, Beleta, Jorge, additional, Berglind, A., additional, Berton, A., additional, Bochenek, Grazyna, additional, Braun, Armin, additional, Campagna, D., additional, Carayannopoulos, Leon, additional, Casaulta, C., additional, Chaleckis, Romanas, additional, Dahlén, B., additional, Davison, imothy, additional, De Alba, Jorge, additional, De Lepeleire, Inge, additional, Dekker, Tamara, additional, Delin, Ingrid, additional, Dennison, P., additional, Dijkhuis, Annemiek, additional, Dodson, Paul, additional, Draper, Aleksandra, additional, Dyson, K., additional, Edwards, Jessica, additional, El Hadjam, L., additional, Emma, Rosalia, additional, Ericsson, Magnus, additional, Faulenbach, C., additional, Flood, Breda, additional, Galffy, G., additional, Gallart, Hector, additional, Garissi, D., additional, Gent, J., additional, Gerhardsson de Verdier, M., additional, Gibeon, D., additional, Gomez, Cristina, additional, Gove, Kerry, additional, Gozzard, Neil, additional, Guillmant-Farry, E., additional, Henriksson, E., additional, Hewitt, Lorraine, additional, Hoda, U., additional, Hu, Richard, additional, Hu, Sile, additional, Hu, X., additional, Jeyasingham, E., additional, Johnson, K., additional, Jullian, N., additional, Kamphuis, Juliette, additional, Kennington, Erika J., additional, Kerry, Dyson, additional, Kerry, G., additional, Klüglich, M., additional, Knobel, Hugo, additional, Kolmert, Johan, additional, Konradsen, J.R., additional, Kots, Maxim, additional, Kretsos, Kosmas, additional, Krueger, L., additional, Kuo, Scott, additional, Kupczyk, Maciej, additional, Lambrecht, Bart, additional, Lantz, A.-S., additional, Larminie, Christopher, additional, Larsson, L.X., additional, Latzin, P., additional, Lazarinis, N., additional, Lemonnier, N., additional, Lone-Latif, Saeeda, additional, Lowe, L.A., additional, Manta, Alexander, additional, Marouzet, Lisa, additional, Martin, Jane, additional, Mathon, Caroline, additional, McEvoy, L., additional, Meah, Sally, additional, Menzies-Gow, A., additional, Metcalf, Leanne, additional, Mikus, Maria, additional, Monk, Philip, additional, Naz, Shama, additional, Nething, K., additional, Nicholas, Ben, additional, Nihlén, U., additional, Nilsson, Peter, additional, Niven, R., additional, Nordlund, B., additional, Nsubuga, S., additional, Pacino, Antonio, additional, Palkonen, Susanna, additional, Pellet, J., additional, Pennazza, Giorgio, additional, Petrén, Anne, additional, Pink, Sandy, additional, Pison, C., additional, Postle, Anthony, additional, Rahman-Amin, Malayka, additional, Ravanetti, Lara, additional, Ray, Emma, additional, Reinke, Stacey, additional, Reynolds, Leanne, additional, Riemann, K., additional, Robberechts, Martine, additional, Rocha, J.P., additional, Rossios, C., additional, Russell, Kirsty, additional, Rutgers, Michael, additional, Santini, G., additional, Santoninco, Marco, additional, Saqi, M., additional, Schoelch, Corinna, additional, Scott, S., additional, Sehgal, N., additional, Sjödin, Marcus, additional, Smids, Barbara, additional, Smith, Caroline, additional, Smith, Jessica, additional, Smith, Katherine M., additional, Söderman, P., additional, Sogbessan, A., additional, Spycher, F., additional, Staykova, Doroteya, additional, Stephan, S., additional, Stokholm, J., additional, Strandberg, K., additional, Sunther, M., additional, Szentkereszty, M., additional, Tamasi, L., additional, Tariq, K., additional, Thörngren, John-Olof, additional, Thorsen, Jonathan, additional, Valente, S., additional, van de Pol, Marianne, additional, van Drunen, C.M., additional, Van Eyll, Jonathan, additional, Versnel, Jenny, additional, Vink, Anton, additional, von Garnier, C., additional, Vyas, A., additional, Wald, Frans, additional, Walker, Samantha, additional, Wetzel, Kristiane, additional, Wiegman, Coen, additional, Williams, Siân, additional, Yang, Xian, additional, Yeyasingham, Elizabeth, additional, Amgen, W. Yu, additional, Zetterquist, W., additional, Zolkipli, Z., additional, and Zwinderman, A.H., additional

Published
2019
Full Text
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15. Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story: Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015

Author

Bousquet, J., Anto, J. M., Akdis, M., Auffray, C., Keil, T., Momas, I., Postma, D. S., Valenta, R., Wickman, M., Cambon-Thomsen, A., Haahtela, T., Lambrecht, B. N., Carlsen, K. C. Lodrup, Koppelman, G. H., Sunyer, J., Zuberbier, T., Annesi-Maesano, I., Arno, A., Bindslev-Jensen, C., De Carlo, G., Forastiere, F., Heinrich, J., Kowalski, M. L., Maier, D., Melen, E., Palkonen, S., Smit, H. A., Standl, M., Wright, J., Asarnoj, A., Benet, M., Ballardini, N., Garcia-Aymerich, J., Gehring, U., Guerra, S., Hohman, C., Kull, I., Lupinek, C., Pinart, M., Skrindo, I., Westman, M., Smagghe, D., Akdis, C., Albang, R., Anastasova, V., Anderson, N., Bachert, C., Ballereau, S., Ballester, F., Basagana, X., Bedbrook, A., Bergstrom, A., von Berg, A., Brunekreef, B., Burte, E., Carlsen, K. H., Chatzi, L., Coquet, J. M., Curin, M., Demoly, P., Eller, E., Fantini, M. P., Gerhard, B., Hammad, H., von Hertzen, L., Hovland, V., Jacquemin, B., Just, J., Keller, T., Kerkhof, M., Kiss, R., Kogevinas, M., Koletzko, S., Lau, S., Lehmann, I., Lemonnier, N., McEachan, R., Makela, M., Mestres, J., Minina, E., Mowinckel, P., Nadif, R., Nawijn, M., Oddie, S., Pellet, J., Pin, I., Porta, D., Ranciere, F., Rial-Sebbag, A., Saeys, Y., Schuijs, M. J., Siroux, V., Tischer, C. G., Torrent, M., Varraso, R., De Vocht, J., Wenger, K., Wieser, S., Xu, C., dIRAS RA-2, Risk Assessment, Clinicum, Department of Dermatology, Allergology and Venereology, Bousquet, J., Anto, J.M., Akdis, M., Auffray, C., Keil, T., Momas, I., Postma, D.S., Valenta, R., Wickman, M., Cambon-Thomsen, A., Haahtela, T., Lambrecht, B.N., Lodrup Carlsen, K.C., Koppelman, G.H., Sunyer, J., Zuberbier, T., Annesi-Maesano, I., Arno, A., Bindslev-Jensen, C., De Carlo, G., Forastiere, F., Heinrich, J., Kowalski, M.L., Maier, D., Melén, E., Palkonen, S., Smit, H.A., Standl, M., Wright, J., Asarnoj, A., Benet, M., Ballardini, N., Garcia-Aymerich, J., Gehring, U., Guerra, S., Hohman, C., Kull, I., Lupinek, C., Pinart, M., Skrindo, I., Westman, M., Smagghe, D., Akdis, C., Albang, R., Anastasova, V., Anderson, N., Bachert, C., Ballereau, S., Ballester, F., Basagana, X., Bedbrook, A., Bergstrom, A., von Berg, A., Brunekreef, B., Burte, E., Carlsen, K.H., Chatzi, L., Coquet, J.M., Curin, M., Demoly, P., Eller, E., Fantini, M.P., Gerhard, B., Hammad, H., von Hertzen, L., Hovland, V., Jacquemin, B., Just, J., Keller, T., Kerkhof, M., Kiss, R., Kogevinas, M., Koletzko, S., Lau, S., Lehmann, I., Lemonnier, N., Mceachan, R., Mäkelä, M., Mestres, J., Minina, E., Mowinckel, P., Nadif, R., Nawijn, M., Oddie, S., Pellet, J., Pin, I., Porta, D., Rancière, F., Rial-Sebbag, A., Saeys, Y., Schuijs, M.J., Siroux, V., Tischer, C.G., Torrent, M., Varraso, R., De Vocht, J., Wenger, K., Wieser, S., and Xu, C.

Subjects
multimorbidity, EUROPEAN INNOVATION PARTNERSHIP, humanos, Immunology, IGE SENSITIZATION, política de salud, Review, rhinitis, Inventions, Unión Europea, Hypersensitivity, Medicine and Health Sciences, Journal Article, Humans, Immunology and Allergy, ATOPIC-DERMATITIS, European Union, biología de sistemas, hipersensibilidad, inmunización, inmunoglobulina E, Asthma, Ige, Multimorbidity, Polysensitization, Rhinitis, BIRTH COHORT, IMMUNE-RESPONSES, Health Policy, Systems Biology, asthma, IgE, polysensitization, CHILDHOOD ASTHMA, invenciones, Immunoglobulin E, Prognosis, INTEGRATED CARE, pronóstico, rhiniti, CHRONIC RESPIRATORY-DISEASES, 3121 General medicine, internal medicine and other clinical medicine, Immunization, IMMUNOLOGICAL REACTIVITY, IMMUNOGLOBULIN-E
Abstract

MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.

Published
2016

16. DNA methylation in childhood asthma: an epigenome-wide meta-analysis

Author

Xu, C.J., Soderhall, C., Bustamante, M., Baiz, N., Gruzieva, O., Gehring, U., Mason, D., Chatzi, L., Basterrechea, M., Llop, S., Torrent, M., Forastiere, F., Fantini, M.P., Carlsen, K.C.L., Haahtela, T., Morin, A., Kerkhof, M. van de, Merid, S.K., Rijkom, B. van, Jankipersadsing, S.A., Bonder, M.J., Ballereau, S., Vermeulen, C.J., Aguirre-Gamboa, R., Jongste, J.C. de, Smit, H.A., Kumar, A., Pershagen, G., Guerra, S., Garcia-Aymerich, J., Greco, D., Reinius, L., McEachan, R.R.C., Azad, R., Hovland, V., Mowinckel, P., Alenius, H., Fyhrquist, N., Lemonnier, N., Pellet, J., Auffray, C., Vlies, P., Diemen, C.C. van, Li, Y., Wijmenga, C., Netea, M.G., Moffatt, M.F., Cookson, W., Anto, J.M., Bousquet, J., Laatikainen, T., Laprise, C., Carlsen, K.H., Gori, D., Porta, D., Iniguez, C., Bilbao, J.R., Kogevinas, M., Wright, J., Brunekreef, B., Kere, J., Nawijn, M.C., Annesi-Maesano, I., Sunyer, J., Melen, E., Koppelman, G.H., Xu, C.J., Soderhall, C., Bustamante, M., Baiz, N., Gruzieva, O., Gehring, U., Mason, D., Chatzi, L., Basterrechea, M., Llop, S., Torrent, M., Forastiere, F., Fantini, M.P., Carlsen, K.C.L., Haahtela, T., Morin, A., Kerkhof, M. van de, Merid, S.K., Rijkom, B. van, Jankipersadsing, S.A., Bonder, M.J., Ballereau, S., Vermeulen, C.J., Aguirre-Gamboa, R., Jongste, J.C. de, Smit, H.A., Kumar, A., Pershagen, G., Guerra, S., Garcia-Aymerich, J., Greco, D., Reinius, L., McEachan, R.R.C., Azad, R., Hovland, V., Mowinckel, P., Alenius, H., Fyhrquist, N., Lemonnier, N., Pellet, J., Auffray, C., Vlies, P., Diemen, C.C. van, Li, Y., Wijmenga, C., Netea, M.G., Moffatt, M.F., Cookson, W., Anto, J.M., Bousquet, J., Laatikainen, T., Laprise, C., Carlsen, K.H., Gori, D., Porta, D., Iniguez, C., Bilbao, J.R., Kogevinas, M., Wright, J., Brunekreef, B., Kere, J., Nawijn, M.C., Annesi-Maesano, I., Sunyer, J., Melen, E., and Koppelman, G.H.

Abstract

Contains fulltext : 193339.pdf (publisher's version ) (Closed access), BACKGROUND: DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma. METHODS: We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blood in 207 children with asthma and 610 controls at age 4-5 years, and 185 children with asthma and 546 controls at age 8 years using a cross-sectional case-control design. After identification of differentially methylated CpG sites in the discovery analysis, we did a validation study in children (4-16 years; 247 cases and 2949 controls) from six additional European cohorts and meta-analysed the results. We next investigated whether replicated CpG sites in cord blood predict later asthma in 1316 children. We subsequently investigated cell-type-specific methylation of the identified CpG sites in eosinophils and respiratory epithelial cells and their related gene-expression signatures. We studied cell-type specificity of the asthma association of the replicated CpG sites in 455 respiratory epithelial cell samples, collected by nasal brushing of 16-year-old children as well as in DNA isolated from blood eosinophils (16 with asthma, eight controls [age 2-56 years]) and compared this with whole-blood DNA samples of 74 individuals with asthma and 93 controls (age 1-79 years). Whole-blood transcriptional profiles associated with replicated CpG sites were annotated using RNA-seq data of subsets of peripheral blood mononuclear cells sorted by fluorescence-activated cell sorting. FINDINGS: 27 methylated CpG sites were identified in the discovery analysis. 14 of these CpG sites were replicated and passed genome-wide significance (p<1.14 x 10(-7)) after meta-analysis. Consistently lower methylation le

Published
2018

17. Computational analysis of multimorbidity between asthma, eczema and rhinitis

Author

Aguilar, D. (Daniel), Pinart, M. (Mariona), Koppelman, G.H. (Gerard), Saeys, Y. (Yvan), Nawijn, M.C. (Martijn), Postma, D.S. (Dirkje), Akdis, C.A., Auffray, C. (C.), Ballereau, S. (Stephane), Benet, M. (M.), Garcõa-Aymerich, J. (Judith), Ramon Gonzalez, J. (Juan), Guerra, S. (Stefano), Keil, M. (Mark), Kogevinas, M. (Manolis), Lambrecht, B.N.M. (Bart), Lemonnier, N. (Nathanael), Melén, E. (Erik), Sunyer, J. (Jordi), Valenta, R., Valverde, S. (Sergi), Wickman, M. (Magnus), Bousquet, J. (Jean), Oliva, B. (Baldomero), Anto, J.M. (Josep), Aguilar, D. (Daniel), Pinart, M. (Mariona), Koppelman, G.H. (Gerard), Saeys, Y. (Yvan), Nawijn, M.C. (Martijn), Postma, D.S. (Dirkje), Akdis, C.A., Auffray, C. (C.), Ballereau, S. (Stephane), Benet, M. (M.), Garcõa-Aymerich, J. (Judith), Ramon Gonzalez, J. (Juan), Guerra, S. (Stefano), Keil, M. (Mark), Kogevinas, M. (Manolis), Lambrecht, B.N.M. (Bart), Lemonnier, N. (Nathanael), Melén, E. (Erik), Sunyer, J. (Jordi), Valenta, R., Valverde, S. (Sergi), Wickman, M. (Magnus), Bousquet, J. (Jean), Oliva, B. (Baldomero), and Anto, J.M. (Josep)

Abstract

Background The mechanisms explaining the co-existence of asthma, eczema and rhinitis (allergic multimorbidity) are largely unknown. We investigated the mechanisms underlying multimorbidity between three main allergic diseases at a molecular level by identifying the proteins and cellular processes that are common to them. Methods An in silico study based on computational analysis of the topology of the protein interaction network was performed in order to characterize the molecular mechanisms of multimorbidity of asthma, eczema and rhinitis. As a first step, proteins associated to either disease were identified using data mining approaches, and their overlap was calculated. Secondly, a functional interaction network was built, allowing to identify cellular pathways involved in allergic multimorbidity. Finally, a network-based algorithm generated a ranked list of newly predicted multimorbidity-associated proteins. Results Asthma, eczema and rhinitis shared a larger number of associated proteins than expected by chance, and their associated proteins exhibited a significant degree of interconnectedness in the interaction network. There were 15 pathways involved in the multimorbidity of asthma, eczema and rhinitis, includin

Published
2017
Full Text
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18. Mechanisms of the Development of Allergy (MeDALL): Introducing novel concepts in allergy phenotypes

Author

Anto, J.M., Bousquet, J., Akdis, M., Auffray, C., Keil, T., Momas, I., Postma, D.S., Valenta, R., Wickman, M., Cambon-Thomsen, A., Haahtela, T., Lambrecht, B.N., Lodrup Carlsen, K.C., Koppelman, G.H., Sunyer, J., Zuberbier, T., Annesi-Maesano, I., Arno, A., Bindslev-Jensen, C., De Carlo, G., Forastiere, F., Heinrich, J., Kowalski, M.L., Maier, D., Melén, E., Smit, H.A., Standl, M., Wright, J., Asarnoj, A., Benet, M., Ballardini, N., Garcia-Aymerich, J., Gehring, U., Guerra, S., Hohmann, C., Kull, I., Lupinek, C., Pinart, M., Skrindo, I., Westman, M., Smagghe, D., Akdis, C., Andersson, N., Bachert, C., Ballereau, S., Ballester, F., Basagana, X., Bedbrook, A., Bergstrom, A., von Berg, A., Brunekreef, B., Burte, E., Carlsen, K.-H., Chatzi, L., Coquet, J.M., Curin, M., Demoly, P., Eller, E., Fantini, M.P., von Hertzen, L., Hovland, V., Jacquemin, B., Just, J., Keller, T., Kiss, R., Kogevinas, M., Koletzko, S., Lau, S., Lehmann, Irina, Lemonnier, N., Mäkelä, M., Mestres, J., Mowinckel, P., Nadif, R., Nawijn, M.C., Pellet, J., Pin, I., Porta, D., Rancière, F., Rial-Sebbag, E., Saeys, Y., Schuijs, M.J., Siroux, V., Tischer, C.G., Torrent, M., Varraso, R., Wenzel, K., Xu, C.-J., Anto, J.M., Bousquet, J., Akdis, M., Auffray, C., Keil, T., Momas, I., Postma, D.S., Valenta, R., Wickman, M., Cambon-Thomsen, A., Haahtela, T., Lambrecht, B.N., Lodrup Carlsen, K.C., Koppelman, G.H., Sunyer, J., Zuberbier, T., Annesi-Maesano, I., Arno, A., Bindslev-Jensen, C., De Carlo, G., Forastiere, F., Heinrich, J., Kowalski, M.L., Maier, D., Melén, E., Smit, H.A., Standl, M., Wright, J., Asarnoj, A., Benet, M., Ballardini, N., Garcia-Aymerich, J., Gehring, U., Guerra, S., Hohmann, C., Kull, I., Lupinek, C., Pinart, M., Skrindo, I., Westman, M., Smagghe, D., Akdis, C., Andersson, N., Bachert, C., Ballereau, S., Ballester, F., Basagana, X., Bedbrook, A., Bergstrom, A., von Berg, A., Brunekreef, B., Burte, E., Carlsen, K.-H., Chatzi, L., Coquet, J.M., Curin, M., Demoly, P., Eller, E., Fantini, M.P., von Hertzen, L., Hovland, V., Jacquemin, B., Just, J., Keller, T., Kiss, R., Kogevinas, M., Koletzko, S., Lau, S., Lehmann, Irina, Lemonnier, N., Mäkelä, M., Mestres, J., Mowinckel, P., Nadif, R., Nawijn, M.C., Pellet, J., Pin, I., Porta, D., Rancière, F., Rial-Sebbag, E., Saeys, Y., Schuijs, M.J., Siroux, V., Tischer, C.G., Torrent, M., Varraso, R., Wenzel, K., and Xu, C.-J.

Abstract

Asthma, rhinitis, and eczema are complex diseases with multiple genetic and environmental factors interlinked through IgE-associated and non–IgE-associated mechanisms. Mechanisms of the Development of ALLergy (MeDALL; EU FP7-CP-IP; project no: 261357; 2010-2015) studied the complex links of allergic diseases at the clinical and mechanistic levels by linking epidemiologic, clinical, and mechanistic research, including in vivo and in vitro models. MeDALL integrated 14 European birth cohorts, including 44,010 participants and 160 cohort follow-ups between pregnancy and age 20 years. Thirteen thousand children were prospectively followed after puberty by using a newly standardized MeDALL Core Questionnaire. A microarray developed for allergen molecules with increased IgE sensitivity was obtained for 3,292 children. Estimates of air pollution exposure from previous studies were available for 10,000 children. Omics data included those from historical genome-wide association studies (23,000 children) and DNA methylation (2,173), targeted multiplex biomarker (1,427), and transcriptomic (723) studies. Using classical epidemiology and machine-learning methods in 16,147 children aged 4 years and 11,080 children aged 8 years, MeDALL showed the multimorbidity of eczema, rhinitis, and asthma and estimated that only 38% of multimorbidity was attributable to IgE sensitization. MeDALL has proposed a new vision of multimorbidity independent of IgE sensitization, and has shown that monosensitization and polysensitization represent 2 distinct phenotypes. The translational component of MeDALL is shown by the identification of a novel allergic phenotype characterized by polysensitization and multimorbidity, which is associated with the frequency, persistence, and severity of allergic symptoms. The results of MeDALL will help integrate personalized, predictive, preventative, and participatory approaches in allergic diseases.

Published
2017

19. Computational analysis of multimorbidity between asthma, eczema and rhinitis

Author

Aguilar, D, Pinart, M, Koppelman, GH, Saeys, Y, Nawijn, MC, Postma, DS, Akdis, M, Auffray, C, Ballereau, S, Benet, M, Garcia-Aymerich, J, Gonzalez, JR, Guerra, S, Keil, T, Kogevinas, M, Lambrecht, Bart, Lemonnier, N, Melen, E, Sunyer, J, Valenta, R, Valverde, S, Wickman, M, Bousquet, J, Oliva, B, Anto, JM, Aguilar, D, Pinart, M, Koppelman, GH, Saeys, Y, Nawijn, MC, Postma, DS, Akdis, M, Auffray, C, Ballereau, S, Benet, M, Garcia-Aymerich, J, Gonzalez, JR, Guerra, S, Keil, T, Kogevinas, M, Lambrecht, Bart, Lemonnier, N, Melen, E, Sunyer, J, Valenta, R, Valverde, S, Wickman, M, Bousquet, J, Oliva, B, and Anto, JM

Published
2017

20. Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story Mechanisms of the Development of ALLergy; EUFP7-CP-IP; Project No: 261357; 2010-2015

Author

Bousquet, J., Anto, J. M., Akdis, M., Auffray, C., Keil, T., Momas, I., Postma, D. S., Valenta, R., Wickman, M., Cambon-Thomsen, A., Haahtela, T., Lambrecht, B. N., Lodrup Carlsen, K. C., Koppelman, G. H., Sunyer, J., Zuberbier, T., Annesi-Maesano, I., Arno, A., Bindslev-Jensen, C., De Carlo, G., Forastiere, F., Heinrich, J., Kowalski, M. L., Maier, D., Melen, E., Palkonen, S., Smit, H. A., Standl, M., Wright, J., Asarnoj, A., Benet, M., Ballardini, N., Garcia-Aymerich, J., Gehring, U., Guerra, S., Hohman, C., Kull, I., Lupinek, C., Pinart, M., Skrindo, I., Westman, M., Smagghe, D., Akdis, C., Albang, R., Anastasova, V., Anderson, N., Bachert, C., Ballereau, S., Ballester, F., Basagana, X., Bedbrook, A., Bergstrom, A., von Berg, A., Brunekreef, B., Burte, E., Carlsen, K.H., Chatzi, L., Coquet, J.M., Curin, M., Demoly, P., Eller, E., Fantini, M.P., Gerhard, B., Hammad, H., von Hertzen, L., Hovland, V., Jacquemin, B., Just, J., Keller, T., Kerkhof, M., Kiss, R., Kogevinas, M., Koletzko, S., Lau, S., Lehmann, I., Lemonnier, N., McEachan, R., Makela, M., Mestres, J., Minina, E., Mowinckel, P., Nadif, R., Nawijn, M., Oddie, S., Pellet, J., Pin, I., Porta, D., Rancière, F., Rial-Sebbag, A., Schuijs, M.J., Siroux, V., Tischer, C.G., Torrent, M., Varraso, R., De Vocht, J., Wenger, K., Wieser, S., and Xu, C.

Subjects
ddc:610
Abstract

MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.

Published
2016

21. Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story: Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015

Author

Bousquet, J, Anto, J M, Akdis, M, Auffray, C, Keil, T, Momas, I, Postma, D S, Valenta, R, Wickman, M, Cambon-Thomsen, A, Haahtela, T, Lambrecht, B N, Lodrup Carlsen, K C, Koppelman, G H, Sunyer, J, Zuberbier, T, Annesi-Maesano, I, Arno, A, Bindslev-Jensen, C, De Carlo, G, Forastiere, F, Heinrich, J, Kowalski, M L, Maier, D, Melén, E, Palkonen, S, Smit, H A, Standl, M, Wright, J, Asarnoj, A, Benet, M, Ballardini, N, Garcia-Aymerich, J, Gehring, U, Guerra, S, Hohman, C, Kull, I, Lupinek, C, Pinart, M, Skrindo, I, Westman, M, Smagghe, D, Akdis, C, Albang, R, Anastasova, V, Anderson, N, Bachert, C, Ballereau, S, Ballester, F, Basagana, X, Bedbrook, A, Bergstrom, A, von Berg, A, Brunekreef, B, Burte, E, Carlsen, K H, Chatzi, L, Coquet, J M, Curin, M, Demoly, P, Eller, E, Fantini, M P, Gerhard, B, Hammad, H, von Hertzen, L, Hovland, V, Jacquemin, B, Just, J, Keller, T, Kerkhof, M, Kiss, R, Kogevinas, M, Koletzko, S, Lau, S, Lehmann, I, Lemonnier, N, McEachan, R, Mäkelä, M, Mestres, J, Minina, E, Mowinckel, P, Nadif, R, Nawijn, M, Oddie, S, Pellet, J, Pin, I, Porta, D, Rancière, F, Rial-Sebbag, A, Saeys, Y, Schuijs, M J, Siroux, V, Tischer, C G, Torrent, M, Varraso, R, De Vocht, J, Wenger, K, Wieser, S, Xu, C, Bousquet, J, Anto, J M, Akdis, M, Auffray, C, Keil, T, Momas, I, Postma, D S, Valenta, R, Wickman, M, Cambon-Thomsen, A, Haahtela, T, Lambrecht, B N, Lodrup Carlsen, K C, Koppelman, G H, Sunyer, J, Zuberbier, T, Annesi-Maesano, I, Arno, A, Bindslev-Jensen, C, De Carlo, G, Forastiere, F, Heinrich, J, Kowalski, M L, Maier, D, Melén, E, Palkonen, S, Smit, H A, Standl, M, Wright, J, Asarnoj, A, Benet, M, Ballardini, N, Garcia-Aymerich, J, Gehring, U, Guerra, S, Hohman, C, Kull, I, Lupinek, C, Pinart, M, Skrindo, I, Westman, M, Smagghe, D, Akdis, C, Albang, R, Anastasova, V, Anderson, N, Bachert, C, Ballereau, S, Ballester, F, Basagana, X, Bedbrook, A, Bergstrom, A, von Berg, A, Brunekreef, B, Burte, E, Carlsen, K H, Chatzi, L, Coquet, J M, Curin, M, Demoly, P, Eller, E, Fantini, M P, Gerhard, B, Hammad, H, von Hertzen, L, Hovland, V, Jacquemin, B, Just, J, Keller, T, Kerkhof, M, Kiss, R, Kogevinas, M, Koletzko, S, Lau, S, Lehmann, I, Lemonnier, N, McEachan, R, Mäkelä, M, Mestres, J, Minina, E, Mowinckel, P, Nadif, R, Nawijn, M, Oddie, S, Pellet, J, Pin, I, Porta, D, Rancière, F, Rial-Sebbag, A, Saeys, Y, Schuijs, M J, Siroux, V, Tischer, C G, Torrent, M, Varraso, R, De Vocht, J, Wenger, K, Wieser, S, and Xu, C

Abstract

MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.

Published
2016

22. Paving the way of systems biology and precision medicine in allergic diseases

Author

University of Helsinki, Clinicum, University of Helsinki, Departments of Dermatology, Allergology and Venereology, Bousquet, J., Anto, J. M., Akdis, M., Auffray, C., Keil, T., Momas, I., Postma, D. S., Valenta, R., Wickman, M., Cambon-Thomsen, A., Haahtela, T., Lambrecht, B. N., Carlsen, K. C. Lodrup, Koppelman, G. H., Sunyer, J., Zuberbier, T., Annesi-Maesano, I., Arno, A., Bindslev-Jensen, C., De Carlo, G., Forastiere, F., Heinrich, J., Kowalski, M. L., Maier, D., Melen, E., Palkonen, S., Smit, H. A., Standl, M., Wright, J., Asarnoj, A., Benet, M., Ballardini, N., Garcia-Aymerich, J., Gehring, U., Guerra, S., Hohman, C., Kull, I., Lupinek, C., Pinart, M., Skrindo, I., Westman, M., Smagghe, D., Akdis, C., Albang, R., Anastasova, V., Anderson, N., Bachert, C., Ballereau, S., Ballester, F., Basagana, X., Bedbrook, A., Bergstrom, A., von Berg, A., Brunekreef, B., Burte, E., Carlsen, K. H., Chatzi, L., Coquet, J. M., Curin, M., Demoly, P., Eller, E., Fantini, M. P., Gerhard, B., Hammad, H., von Hertzen, L., Hovland, V., Jacquemin, B., Just, J., Keller, T., Kerkhof, M., Kiss, R., Kogevinas, M., Koletzko, S., Lau, S., Lehmann, I., Lemonnier, N., McEachan, R., Mäkelä, M., Mestres, J., Minina, E., Mowinckel, P., Nadif, R., Nawijn, M., Oddie, S., Pellet, J., Pin, I., Porta, D., Ranciere, F., Rial-Sebbag, A., Saeys, Y., Schuijs, M. J., Siroux, V., Tischer, C. G., Torrent, M., Varraso, R., De Vocht, J., Wenger, K., Wieser, S., Xu, C., University of Helsinki, Clinicum, University of Helsinki, Departments of Dermatology, Allergology and Venereology, Bousquet, J., Anto, J. M., Akdis, M., Auffray, C., Keil, T., Momas, I., Postma, D. S., Valenta, R., Wickman, M., Cambon-Thomsen, A., Haahtela, T., Lambrecht, B. N., Carlsen, K. C. Lodrup, Koppelman, G. H., Sunyer, J., Zuberbier, T., Annesi-Maesano, I., Arno, A., Bindslev-Jensen, C., De Carlo, G., Forastiere, F., Heinrich, J., Kowalski, M. L., Maier, D., Melen, E., Palkonen, S., Smit, H. A., Standl, M., Wright, J., Asarnoj, A., Benet, M., Ballardini, N., Garcia-Aymerich, J., Gehring, U., Guerra, S., Hohman, C., Kull, I., Lupinek, C., Pinart, M., Skrindo, I., Westman, M., Smagghe, D., Akdis, C., Albang, R., Anastasova, V., Anderson, N., Bachert, C., Ballereau, S., Ballester, F., Basagana, X., Bedbrook, A., Bergstrom, A., von Berg, A., Brunekreef, B., Burte, E., Carlsen, K. H., Chatzi, L., Coquet, J. M., Curin, M., Demoly, P., Eller, E., Fantini, M. P., Gerhard, B., Hammad, H., von Hertzen, L., Hovland, V., Jacquemin, B., Just, J., Keller, T., Kerkhof, M., Kiss, R., Kogevinas, M., Koletzko, S., Lau, S., Lehmann, I., Lemonnier, N., McEachan, R., Mäkelä, M., Mestres, J., Minina, E., Mowinckel, P., Nadif, R., Nawijn, M., Oddie, S., Pellet, J., Pin, I., Porta, D., Ranciere, F., Rial-Sebbag, A., Saeys, Y., Schuijs, M. J., Siroux, V., Tischer, C. G., Torrent, M., Varraso, R., De Vocht, J., Wenger, K., Wieser, S., and Xu, C.

Abstract

MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.

Published
2016

23. Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story: Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015

Author

dIRAS RA-2, Risk Assessment, Bousquet, J, Anto, J M, Akdis, M, Auffray, C, Keil, T, Momas, I, Postma, D S, Valenta, R, Wickman, M, Cambon-Thomsen, A, Haahtela, T, Lambrecht, B N, Lodrup Carlsen, K C, Koppelman, G H, Sunyer, J, Zuberbier, T, Annesi-Maesano, I, Arno, A, Bindslev-Jensen, C, De Carlo, G, Forastiere, F, Heinrich, J, Kowalski, M L, Maier, D, Melén, E, Palkonen, S, Smit, H A, Standl, M, Wright, J, Asarnoj, A, Benet, M, Ballardini, N, Garcia-Aymerich, J, Gehring, U, Guerra, S, Hohman, C, Kull, I, Lupinek, C, Pinart, M, Skrindo, I, Westman, M, Smagghe, D, Akdis, C, Albang, R, Anastasova, V, Anderson, N, Bachert, C, Ballereau, S, Ballester, F, Basagana, X, Bedbrook, A, Bergstrom, A, von Berg, A, Brunekreef, B, Burte, E, Carlsen, K H, Chatzi, L, Coquet, J M, Curin, M, Demoly, P, Eller, E, Fantini, M P, Gerhard, B, Hammad, H, von Hertzen, L, Hovland, V, Jacquemin, B, Just, J, Keller, T, Kerkhof, M, Kiss, R, Kogevinas, M, Koletzko, S, Lau, S, Lehmann, I, Lemonnier, N, McEachan, R, Mäkelä, M, Mestres, J, Minina, E, Mowinckel, P, Nadif, R, Nawijn, M, Oddie, S, Pellet, J, Pin, I, Porta, D, Rancière, F, Rial-Sebbag, A, Saeys, Y, Schuijs, M J, Siroux, V, Tischer, C G, Torrent, M, Varraso, R, De Vocht, J, Wenger, K, Wieser, S, Xu, C, dIRAS RA-2, Risk Assessment, Bousquet, J, Anto, J M, Akdis, M, Auffray, C, Keil, T, Momas, I, Postma, D S, Valenta, R, Wickman, M, Cambon-Thomsen, A, Haahtela, T, Lambrecht, B N, Lodrup Carlsen, K C, Koppelman, G H, Sunyer, J, Zuberbier, T, Annesi-Maesano, I, Arno, A, Bindslev-Jensen, C, De Carlo, G, Forastiere, F, Heinrich, J, Kowalski, M L, Maier, D, Melén, E, Palkonen, S, Smit, H A, Standl, M, Wright, J, Asarnoj, A, Benet, M, Ballardini, N, Garcia-Aymerich, J, Gehring, U, Guerra, S, Hohman, C, Kull, I, Lupinek, C, Pinart, M, Skrindo, I, Westman, M, Smagghe, D, Akdis, C, Albang, R, Anastasova, V, Anderson, N, Bachert, C, Ballereau, S, Ballester, F, Basagana, X, Bedbrook, A, Bergstrom, A, von Berg, A, Brunekreef, B, Burte, E, Carlsen, K H, Chatzi, L, Coquet, J M, Curin, M, Demoly, P, Eller, E, Fantini, M P, Gerhard, B, Hammad, H, von Hertzen, L, Hovland, V, Jacquemin, B, Just, J, Keller, T, Kerkhof, M, Kiss, R, Kogevinas, M, Koletzko, S, Lau, S, Lehmann, I, Lemonnier, N, McEachan, R, Mäkelä, M, Mestres, J, Minina, E, Mowinckel, P, Nadif, R, Nawijn, M, Oddie, S, Pellet, J, Pin, I, Porta, D, Rancière, F, Rial-Sebbag, A, Saeys, Y, Schuijs, M J, Siroux, V, Tischer, C G, Torrent, M, Varraso, R, De Vocht, J, Wenger, K, Wieser, S, and Xu, C

Published
2016

24. Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story: Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015

Author

Circulatory Health, Child Health, JC onderzoeksprogramma Infectieziekten, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Public Health Epidemiologie, Epi Infectieziekten Team 3, Infection & Immunity, Bousquet, J, Anto, J M, Akdis, M, Auffray, C, Keil, T, Momas, I, Postma, D S, Valenta, R, Wickman, M, Cambon-Thomsen, A, Haahtela, T, Lambrecht, B N, Lodrup Carlsen, K C, Koppelman, G H, Sunyer, J, Zuberbier, T, Annesi-Maesano, I, Arno, A, Bindslev-Jensen, C, De Carlo, G, Forastiere, F, Heinrich, J, Kowalski, M L, Maier, D, Melén, E, Palkonen, S, Smit, H A, Standl, M, Wright, J, Asarnoj, A, Benet, M, Ballardini, N, Garcia-Aymerich, J, Gehring, U, Guerra, S, Hohman, C, Kull, I, Lupinek, C, Pinart, M, Skrindo, I, Westman, M, Smagghe, D, Akdis, C, Albang, R, Anastasova, V, Anderson, N, Bachert, C, Ballereau, S, Ballester, F, Basagana, X, Bedbrook, A, Bergstrom, A, von Berg, A, Brunekreef, B, Burte, E, Carlsen, K H, Chatzi, L, Coquet, J M, Curin, M, Demoly, P, Eller, E, Fantini, M P, Gerhard, B, Hammad, H, von Hertzen, L, Hovland, V, Jacquemin, B, Just, J, Keller, T, Kerkhof, M, Kiss, R, Kogevinas, M, Koletzko, S, Lau, S, Lehmann, I, Lemonnier, N, McEachan, R, Mäkelä, M, Mestres, J, Minina, E, Mowinckel, P, Nadif, R, Nawijn, M, Oddie, S, Pellet, J, Pin, I, Porta, D, Rancière, F, Rial-Sebbag, A, Saeys, Y, Schuijs, M J, Siroux, V, Tischer, C G, Torrent, M, Varraso, R, De Vocht, J, Wenger, K, Wieser, S, Xu, C, Circulatory Health, Child Health, JC onderzoeksprogramma Infectieziekten, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Public Health Epidemiologie, Epi Infectieziekten Team 3, Infection & Immunity, Bousquet, J, Anto, J M, Akdis, M, Auffray, C, Keil, T, Momas, I, Postma, D S, Valenta, R, Wickman, M, Cambon-Thomsen, A, Haahtela, T, Lambrecht, B N, Lodrup Carlsen, K C, Koppelman, G H, Sunyer, J, Zuberbier, T, Annesi-Maesano, I, Arno, A, Bindslev-Jensen, C, De Carlo, G, Forastiere, F, Heinrich, J, Kowalski, M L, Maier, D, Melén, E, Palkonen, S, Smit, H A, Standl, M, Wright, J, Asarnoj, A, Benet, M, Ballardini, N, Garcia-Aymerich, J, Gehring, U, Guerra, S, Hohman, C, Kull, I, Lupinek, C, Pinart, M, Skrindo, I, Westman, M, Smagghe, D, Akdis, C, Albang, R, Anastasova, V, Anderson, N, Bachert, C, Ballereau, S, Ballester, F, Basagana, X, Bedbrook, A, Bergstrom, A, von Berg, A, Brunekreef, B, Burte, E, Carlsen, K H, Chatzi, L, Coquet, J M, Curin, M, Demoly, P, Eller, E, Fantini, M P, Gerhard, B, Hammad, H, von Hertzen, L, Hovland, V, Jacquemin, B, Just, J, Keller, T, Kerkhof, M, Kiss, R, Kogevinas, M, Koletzko, S, Lau, S, Lehmann, I, Lemonnier, N, McEachan, R, Mäkelä, M, Mestres, J, Minina, E, Mowinckel, P, Nadif, R, Nawijn, M, Oddie, S, Pellet, J, Pin, I, Porta, D, Rancière, F, Rial-Sebbag, A, Saeys, Y, Schuijs, M J, Siroux, V, Tischer, C G, Torrent, M, Varraso, R, De Vocht, J, Wenger, K, Wieser, S, and Xu, C

Published
2016

25. Paving the way of systems biology and precision medicine in allergic diseases: the Me DALL success story

Author

Bousquet, J., primary, Anto, J. M., additional, Akdis, M., additional, Auffray, C., additional, Keil, T., additional, Momas, I., additional, Postma, D.S., additional, Valenta, R., additional, Wickman, M., additional, Cambon‐Thomsen, A., additional, Haahtela, T., additional, Lambrecht, B. N., additional, Lodrup Carlsen, K. C., additional, Koppelman, G. H., additional, Sunyer, J., additional, Zuberbier, T., additional, Annesi‐Maesano, I., additional, Arno, A., additional, Bindslev‐Jensen, C., additional, De Carlo, G., additional, Forastiere, F., additional, Heinrich, J., additional, Kowalski, M. L., additional, Maier, D., additional, Melén, E., additional, Palkonen, S., additional, Smit, H. A., additional, Standl, M., additional, Wright, J., additional, Asarnoj, A., additional, Benet, M., additional, Ballardini, N., additional, Garcia‐Aymerich, J., additional, Gehring, U., additional, Guerra, S., additional, Hohman, C., additional, Kull, I., additional, Lupinek, C., additional, Pinart, M., additional, Skrindo, I., additional, Westman, M., additional, Smagghe, D., additional, Akdis, C., additional, Albang, R., additional, Anastasova, V., additional, Anderson, N., additional, Bachert, C., additional, Ballereau, S., additional, Ballester, F., additional, Basagana, X., additional, Bedbrook, A., additional, Bergstrom, A., additional, Berg, A., additional, Brunekreef, B., additional, Burte, E., additional, Carlsen, K. H., additional, Chatzi, L., additional, Coquet, J. M., additional, Curin, M., additional, Demoly, P., additional, Eller, E., additional, Fantini, M. P., additional, Gerhard, B., additional, Hammad, H., additional, Hertzen, L., additional, Hovland, V., additional, Jacquemin, B., additional, Just, J., additional, Keller, T., additional, Kerkhof, M., additional, Kiss, R., additional, Kogevinas, M., additional, Koletzko, S., additional, Lau, S., additional, Lehmann, I., additional, Lemonnier, N., additional, McEachan, R., additional, Mäkelä, M., additional, Mestres, J., additional, Minina, E., additional, Mowinckel, P., additional, Nadif, R., additional, Nawijn, M., additional, Oddie, S., additional, Pellet, J., additional, Pin, I., additional, Porta, D., additional, Rancière, F., additional, Rial‐Sebbag, A., additional, Saeys, Y., additional, Schuijs, M. J., additional, Siroux, V., additional, Tischer, C. G., additional, Torrent, M., additional, Varraso, R., additional, De Vocht, J., additional, Wenger, K., additional, Wieser, S., additional, and Xu, C., additional

Published
2016
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27. Are allergic multimorbidities and IgE polysensitization associated with the persistence or re-occurrence of foetal type 2 signalling?: The MeDALL hypothesis

Author

Bousquet, J, Anto, J M, Wickman, M, Keil, T, Valenta, R, Haahtela, T, Lodrup Carlsen, K, van Hage, M, Akdis, C, Bachert, C, Akdis, M, Auffray, C, Annesi-Maesano, I, Bindslev-Jensen, C, Cambon-Thomsen, A, Carlsen, K H, Chatzi, L, Forastiere, F, Garcia-Aymerich, J, Gehring, Ulrike, Guerra, S, Heinrich, J, Koppelman, G H, Kowalski, M L, Lambrecht, B, Lupinek, C, Maier, D, Melén, E, Momas, I, Palkonen, S, Pinart, M, Postma, D, Siroux, V, Smit, H A, Sunyer, J, Wright, J, Zuberbier, T, Arshad, S H, Nadif, R, Thijs, C, Andersson, N, Asarnoj, A, Ballardini, N, Ballereau, S, Bedbrook, A, Benet, M, Bergstrom, A, Brunekreef, B, Burte, E, Calderon, M, De Carlo, G, Demoly, P, Eller, E, Fantini, M P, Hammad, H, Hohman, C, Just, J, Kerkhof, M, Kogevinas, M, Kull, I, Lau, S, Lemonnier, N, Mommers, M, Nawijn, M, Neubauer, A, Oddie, S, Pellet, J, Pin, I, Porta, D, Saes, Y, Skrindo, I, Tischer, C G, Torrent, M, von Hertzen, L, Bousquet, J, Anto, J M, Wickman, M, Keil, T, Valenta, R, Haahtela, T, Lodrup Carlsen, K, van Hage, M, Akdis, C, Bachert, C, Akdis, M, Auffray, C, Annesi-Maesano, I, Bindslev-Jensen, C, Cambon-Thomsen, A, Carlsen, K H, Chatzi, L, Forastiere, F, Garcia-Aymerich, J, Gehring, Ulrike, Guerra, S, Heinrich, J, Koppelman, G H, Kowalski, M L, Lambrecht, B, Lupinek, C, Maier, D, Melén, E, Momas, I, Palkonen, S, Pinart, M, Postma, D, Siroux, V, Smit, H A, Sunyer, J, Wright, J, Zuberbier, T, Arshad, S H, Nadif, R, Thijs, C, Andersson, N, Asarnoj, A, Ballardini, N, Ballereau, S, Bedbrook, A, Benet, M, Bergstrom, A, Brunekreef, B, Burte, E, Calderon, M, De Carlo, G, Demoly, P, Eller, E, Fantini, M P, Hammad, H, Hohman, C, Just, J, Kerkhof, M, Kogevinas, M, Kull, I, Lau, S, Lemonnier, N, Mommers, M, Nawijn, M, Neubauer, A, Oddie, S, Pellet, J, Pin, I, Porta, D, Saes, Y, Skrindo, I, Tischer, C G, Torrent, M, and von Hertzen, L

Abstract

Allergic diseases [asthma, rhinitis and atopic dermatitis (AD)] are complex. They are associated with allergen-specific IgE and nonallergic mechanisms that may coexist in the same patient. In addition, these diseases tend to cluster and patients present concomitant or consecutive diseases (multimorbidity). IgE sensitization should be considered as a quantitative trait. Important clinical and immunological differences exist between mono- and polysensitized subjects. Multimorbidities of allergic diseases share common causal mechanisms that are only partly IgE-mediated. Persistence of allergic diseases over time is associated with multimorbidity and/or IgE polysensitization. The importance of the family history of allergy may decrease with age. This review puts forward the hypothesis that allergic multimorbidities and IgE polysensitization are associated and related to the persistence or re-occurrence of foetal type 2 signalling. Asthma, rhinitis and AD are manifestations of a common systemic immune imbalance (mesodermal origin) with specific patterns of remodelling (ectodermal or endodermal origin). This study proposes a new classification of IgE-mediated allergic diseases that allows the definition of novel phenotypes to (i) better understand genetic and epigenetic mechanisms, (ii) better stratify allergic preschool children for prognosis and (iii) propose novel strategies of treatment and prevention.

Published
2015

28. Are allergic multimorbidities and IgE polysensitization associated with the persistence or re-occurrence of foetal type 2 signalling?: The MeDALL hypothesis

Author

LS IRAS EEPI ME (Milieu epidemiologie), Dep IRAS, Risk Assessment of Toxic and Immunomodulatory Agents, IRAS RATIA2, Bousquet, J, Anto, J M, Wickman, M, Keil, T, Valenta, R, Haahtela, T, Lodrup Carlsen, K, van Hage, M, Akdis, C, Bachert, C, Akdis, M, Auffray, C, Annesi-Maesano, I, Bindslev-Jensen, C, Cambon-Thomsen, A, Carlsen, K H, Chatzi, L, Forastiere, F, Garcia-Aymerich, J, Gehring, Ulrike, Guerra, S, Heinrich, J, Koppelman, G H, Kowalski, M L, Lambrecht, B, Lupinek, C, Maier, D, Melén, E, Momas, I, Palkonen, S, Pinart, M, Postma, D, Siroux, V, Smit, H A, Sunyer, J, Wright, J, Zuberbier, T, Arshad, S H, Nadif, R, Thijs, C, Andersson, N, Asarnoj, A, Ballardini, N, Ballereau, S, Bedbrook, A, Benet, M, Bergstrom, A, Brunekreef, B, Burte, E, Calderon, M, De Carlo, G, Demoly, P, Eller, E, Fantini, M P, Hammad, H, Hohman, C, Just, J, Kerkhof, M, Kogevinas, M, Kull, I, Lau, S, Lemonnier, N, Mommers, M, Nawijn, M, Neubauer, A, Oddie, S, Pellet, J, Pin, I, Porta, D, Saes, Y, Skrindo, I, Tischer, C G, Torrent, M, von Hertzen, L, LS IRAS EEPI ME (Milieu epidemiologie), Dep IRAS, Risk Assessment of Toxic and Immunomodulatory Agents, IRAS RATIA2, Bousquet, J, Anto, J M, Wickman, M, Keil, T, Valenta, R, Haahtela, T, Lodrup Carlsen, K, van Hage, M, Akdis, C, Bachert, C, Akdis, M, Auffray, C, Annesi-Maesano, I, Bindslev-Jensen, C, Cambon-Thomsen, A, Carlsen, K H, Chatzi, L, Forastiere, F, Garcia-Aymerich, J, Gehring, Ulrike, Guerra, S, Heinrich, J, Koppelman, G H, Kowalski, M L, Lambrecht, B, Lupinek, C, Maier, D, Melén, E, Momas, I, Palkonen, S, Pinart, M, Postma, D, Siroux, V, Smit, H A, Sunyer, J, Wright, J, Zuberbier, T, Arshad, S H, Nadif, R, Thijs, C, Andersson, N, Asarnoj, A, Ballardini, N, Ballereau, S, Bedbrook, A, Benet, M, Bergstrom, A, Brunekreef, B, Burte, E, Calderon, M, De Carlo, G, Demoly, P, Eller, E, Fantini, M P, Hammad, H, Hohman, C, Just, J, Kerkhof, M, Kogevinas, M, Kull, I, Lau, S, Lemonnier, N, Mommers, M, Nawijn, M, Neubauer, A, Oddie, S, Pellet, J, Pin, I, Porta, D, Saes, Y, Skrindo, I, Tischer, C G, Torrent, M, and von Hertzen, L

Published
2015

29. Are allergic multimorbidities and IgE polysensitization associated with the persistence or re-occurrence of foetal type 2 signalling? The MeDALL hypothesis

Author

Epi Infectieziekten Team 1, Cardiometabolic Health, JC onderzoeksprogramma Infectieziekten, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Epi Infectieziekten Team 3, Infection & Immunity, Bousquet, J., Anto, J. M., Wickman, M., Keil, T., Valenta, R., Haahtela, T., Carlsen, K. Lodrup, van Hage, M., Akdis, C., Bachert, C., Akdis, M., Auffray, C., Annesi-Maesano, I., Bindslev-Jensen, C., Cambon-Thomsen, A., Carlsen, K. H., Chatzi, L., Forastiere, F., Garcia-Aymerich, J., Gehrig, U., Guerra, S., Heinrich, J., Koppelman, G. H., Kowalski, M. L., Lambrecht, B., Lupinek, C., Maier, D., Melen, E., Momas, I., Palkonen, S., Pinart, M., Postma, D., Siroux, V., Smit, H. A., Sunyer, J., Wright, J., Zuberbier, T., Arshad, S. H., Nadif, R., Thijs, C., Andersson, N., Asarnoj, A., Ballardini, N., Ballereau, S., Bedbrook, A., Benet, M., Bergstrom, A., Brunekreef, B., Burte, E., Calderon, M., De Carlo, G., Demoly, P., Eller, E., Fantini, M. P., Hammad, H., Hohman, C., Just, J., Kerkhof, M., Kogevinas, M., Kull, I., Lau, S., Lemonnier, N., Mommers, M., Nawijn, M., Neubauer, A., Oddie, S., Pellet, J., Pin, I., Porta, D., Saes, Y., Skrindo, I., Tischer, C. G., Torrent, M., von Hertzen, L., Epi Infectieziekten Team 1, Cardiometabolic Health, JC onderzoeksprogramma Infectieziekten, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Epi Infectieziekten Team 3, Infection & Immunity, Bousquet, J., Anto, J. M., Wickman, M., Keil, T., Valenta, R., Haahtela, T., Carlsen, K. Lodrup, van Hage, M., Akdis, C., Bachert, C., Akdis, M., Auffray, C., Annesi-Maesano, I., Bindslev-Jensen, C., Cambon-Thomsen, A., Carlsen, K. H., Chatzi, L., Forastiere, F., Garcia-Aymerich, J., Gehrig, U., Guerra, S., Heinrich, J., Koppelman, G. H., Kowalski, M. L., Lambrecht, B., Lupinek, C., Maier, D., Melen, E., Momas, I., Palkonen, S., Pinart, M., Postma, D., Siroux, V., Smit, H. A., Sunyer, J., Wright, J., Zuberbier, T., Arshad, S. H., Nadif, R., Thijs, C., Andersson, N., Asarnoj, A., Ballardini, N., Ballereau, S., Bedbrook, A., Benet, M., Bergstrom, A., Brunekreef, B., Burte, E., Calderon, M., De Carlo, G., Demoly, P., Eller, E., Fantini, M. P., Hammad, H., Hohman, C., Just, J., Kerkhof, M., Kogevinas, M., Kull, I., Lau, S., Lemonnier, N., Mommers, M., Nawijn, M., Neubauer, A., Oddie, S., Pellet, J., Pin, I., Porta, D., Saes, Y., Skrindo, I., Tischer, C. G., Torrent, M., and von Hertzen, L.

Published
2015

30. Cumulative impact of common genetic variants and other risk factors on colorectal cancer risk in 42\u2008103 individuals

Author

Dunlop MG, Tenesa A, Farrington SM, Ballereau S, Brewster DH, Kossler T, Pharoah P, Schafmayer C, Hampe J, Vxf6lzke H, Chang-Claude J, Hoffmeister M, Brenner H, von Holst S, Picelli S, Lindblom A, Jenkins MA, Hopper JL, Casey G, Duggan D, Newcomb PA, Abulıxb4 A, Bessa X, Ruiz-Ponte C, Castellvıxb4-Bel S, Niittymxe4ki I, Tuupanen S, Karhu A, Aaltonen L, Zanke B, Hudson T, Gallinger S, Barclay E, Martin L, Gorman M, Carvajal-Carmona L, Walther A, Kerr D, Lubbe S, Broderick P, Chandler I, Pittman A, Penegar S, and Campbel

Published
2012

32. Functional Genomics, Proteomics, Metabolomics and Bioinformatics for Systems Biology

Author

Luxembourg Centre for Systems Biomedicine (LCSB): Experimental Neurobiology (Balling Group) [research center], Ballereau, S., Glaab, Enrico, Kolodkin, Alexey, Chaiboonchoe, A., Biryukov, Maria, Vlassis, Nikos, Ahmed, H., Pellet, J., Baliga, N., Hood, Leroy, Schneider, Reinhard, Balling, Rudi, Auffray, C., Luxembourg Centre for Systems Biomedicine (LCSB): Experimental Neurobiology (Balling Group) [research center], Ballereau, S., Glaab, Enrico, Kolodkin, Alexey, Chaiboonchoe, A., Biryukov, Maria, Vlassis, Nikos, Ahmed, H., Pellet, J., Baliga, N., Hood, Leroy, Schneider, Reinhard, Balling, Rudi, and Auffray, C.

Abstract

This chapter introduces systems biology, its context, aims, concepts and strategies. It then describes approaches and methods used for collection of high-dimensional structural and functional genomics data, including epigenomics, transcriptomics, proteomics, metabolomics and lipidomics, and how recent technological advances in these fields have moved the bottleneck from data production to data analysis and bioinformatics. Finally, the most advanced mathematical and computational methods used for clustering, feature selection, prediction analysis, text mining and pathway analysis in functional genomics and systems biology are reviewed and discussed in the context of use cases.

Published
2013

33. Computational infrastructures for data and knowledge management in systems biology

Author

Luxembourg Centre for Systems Biomedicine (LCSB): Experimental Neurobiology (Balling Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Georgatos, Fotis, Ballereau, S., Pellet, J., Ghanem, M., Price, N., Hood, Leroy, Guo, Y. K., Boutigny, D., Auffray, C., Balling, Rudi, Schneider, Reinhard, Luxembourg Centre for Systems Biomedicine (LCSB): Experimental Neurobiology (Balling Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Georgatos, Fotis, Ballereau, S., Pellet, J., Ghanem, M., Price, N., Hood, Leroy, Guo, Y. K., Boutigny, D., Auffray, C., Balling, Rudi, and Schneider, Reinhard

Abstract

The volume, complexity and heterogeneity of data originating from high throughput functional genomics technologies have created challenges and opportunities for Information Technology (IT) departments. These increased demands have also led to increasing costs for IT infrastructure such as necessary computing power and storage devices, as well as further costs for manpower effort, required for maintenance. This chapter describes some of the challenges for computational analysis infrastructure, including bottlenecks and most pressing needs that have to be addressed to effectively support the development of systems biology and its application in medicine.

Published
2013

34. Cumulative impact of common genetic variants and other risk factors on colorectal cancer risk in 42 103 individuals

Author

Dunlop, MG, Tenesa, A, Farrington, SM, Ballereau, S, Brewster, DH, Koessler, T, Pharoah, P, Schafmayer, C, Hampe, J, Voelzke, H, Chang-Claude, J, Hoffmeister, M, Brenner, H, von Holst, S, Picelli, S, Lindblom, A, Jenkins, MA, Hopper, JL, Casey, G, Duggan, D, Newcomb, PA, Abuli, A, Bessa, X, Ruiz-Ponte, C, Castellvi-Bel, S, Niittymaeki, I, Tuupanen, S, Karhu, A, Aaltonen, L, Zanke, B, Hudson, T, Gallinger, S, Barclay, E, Martin, L, Gorman, M, Carvajal-Carmona, L, Walther, A, Kerr, D, Lubbe, S, Broderick, P, Chandler, I, Pittman, A, Penegar, S, Campbell, H, Tomlinson, I, Houlston, RS, Dunlop, MG, Tenesa, A, Farrington, SM, Ballereau, S, Brewster, DH, Koessler, T, Pharoah, P, Schafmayer, C, Hampe, J, Voelzke, H, Chang-Claude, J, Hoffmeister, M, Brenner, H, von Holst, S, Picelli, S, Lindblom, A, Jenkins, MA, Hopper, JL, Casey, G, Duggan, D, Newcomb, PA, Abuli, A, Bessa, X, Ruiz-Ponte, C, Castellvi-Bel, S, Niittymaeki, I, Tuupanen, S, Karhu, A, Aaltonen, L, Zanke, B, Hudson, T, Gallinger, S, Barclay, E, Martin, L, Gorman, M, Carvajal-Carmona, L, Walther, A, Kerr, D, Lubbe, S, Broderick, P, Chandler, I, Pittman, A, Penegar, S, Campbell, H, Tomlinson, I, and Houlston, RS

Abstract

OBJECTIVE: Colorectal cancer (CRC) has a substantial heritable component. Common genetic variation has been shown to contribute to CRC risk. A study was conducted in a large multi-population study to assess the feasibility of CRC risk prediction using common genetic variant data combined with other risk factors. A risk prediction model was built and applied to the Scottish population using available data. DESIGN: Nine populations of European descent were studied to develop and validate CRC risk prediction models. Binary logistic regression was used to assess the combined effect of age, gender, family history (FH) and genotypes at 10 susceptibility loci that individually only modestly influence CRC risk. Risk models were generated from case-control data incorporating genotypes alone (n=39,266) and in combination with gender, age and FH (n=11,324). Model discriminatory performance was assessed using 10-fold internal cross-validation and externally using 4187 independent samples. The 10-year absolute risk was estimated by modelling genotype and FH with age- and gender-specific population risks. RESULTS: The median number of risk alleles was greater in cases than controls (10 vs 9, p<2.2 × 10(-16)), confirmed in external validation sets (Sweden p=1.2 × 10(-6), Finland p=2 × 10(-5)). The mean per-allele increase in risk was 9% (OR 1.09; 95% CI 1.05 to 1.13). Discriminative performance was poor across the risk spectrum (area under curve for genotypes alone 0.57; area under curve for genotype/age/gender/FH 0.59). However, modelling genotype data, FH, age and gender with Scottish population data shows the practicalities of identifying a subgroup with >5% predicted 10-year absolute risk. CONCLUSION: Genotype data provide additional information that complements age, gender and FH as risk factors, but individualised genetic risk prediction is not currently feasible. Nonetheless, the modelling exercise suggests public health potential since it is possible to stratify the popula

Published
2013

35. Network analysis for systems biology

Author

Luxembourg Centre for Systems Biomedicine (LCSB): Experimental Neurobiology (Balling Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Computational Biology (Del Sol Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Biomedical Data Science (Glaab Group) [research center], Chaiboonchoe, A., Jurkowski, Wiktor, Pellet, J., Glaab, Enrico, Kolodkin, Alexey, Raussel, Antonio, Le Béchec, Antony, Meyniel, L., Ballereau, S., Crespo, Isaac, Ahmed, H., Volpert, V., Lotteau, V., Baliga, N., Hood, Leroy, del Sol, A., Balling, Rudi, Auffray, C., Luxembourg Centre for Systems Biomedicine (LCSB): Experimental Neurobiology (Balling Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Computational Biology (Del Sol Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Biomedical Data Science (Glaab Group) [research center], Chaiboonchoe, A., Jurkowski, Wiktor, Pellet, J., Glaab, Enrico, Kolodkin, Alexey, Raussel, Antonio, Le Béchec, Antony, Meyniel, L., Ballereau, S., Crespo, Isaac, Ahmed, H., Volpert, V., Lotteau, V., Baliga, N., Hood, Leroy, del Sol, A., Balling, Rudi, and Auffray, C.

Abstract

Network analysis is an essential component of systems biology approaches toward understanding the molecular and cellular interactions underlying biological systems functionalities and their perturbations in disease. Regulatory and signalling pathways, which involve DNA, RNA proteins and metabolites as key elements, coordinate most aspects of cellular functioning. Cellular processes, which are dependent on the structure and dynamics of gene regulatory networks, can be studied by employing a network representation of molecular interactions. In this chapter we describe several types of networks and how combination of different analytic approaches can be used to study diseases. We provide a list of selected tools for visualization and network analysis. We introduce protein-protein interaction networks, gene regulatory networks, signalling networks and metabolic networks. We then define concepts underlying network representation of cellular processes and molecular interactions. We finally discuss how the level of accuracy in inferring functional relationships influences the choice of methods applied for the analysis of a particular network type.

Published
2013

36. Application of 'omics technologies to biomarker discovery in inflammatory lung diseases.

Author

Wheelock, Ce, Goss, Vm, Belgoma, D, Brandsma, J, Skipp, Pj, Snowden, S, Burg, D, D'Amico, A, Horvath, I, Chaiboonchoe, A, Ahmed, H, Ballereau, S, Rossios, C, Chung, Kf, Montuschi, Paolo, Adcock, Im, Postle, Ad, Dahlén, Se, Rowe, A, Sterk, Pj, Auffray, C, Djukanovic, R., Fowler, Sj, Montuschi, Paolo (ORCID:0000-0001-5589-1750), Wheelock, Ce, Goss, Vm, Belgoma, D, Brandsma, J, Skipp, Pj, Snowden, S, Burg, D, D'Amico, A, Horvath, I, Chaiboonchoe, A, Ahmed, H, Ballereau, S, Rossios, C, Chung, Kf, Montuschi, Paolo, Adcock, Im, Postle, Ad, Dahlén, Se, Rowe, A, Sterk, Pj, Auffray, C, Djukanovic, R., Fowler, Sj, and Montuschi, Paolo (ORCID:0000-0001-5589-1750)

Abstract

Inflammatory lung diseases are highly complex in respect of pathogenesis and relationships between inflammation, clinical disease and response to treatment. Sophisticated large-scale analytical methods to quantify gene expression (transcriptomics), proteins (proteomics), lipids (lipidomics) and metabolites (metabolomics) in the lungs, blood and urine are now available to identify biomarkers that define disease in terms of combined clinical, physiological and patho-biological abnormalities. The aspiration is that these approaches will improve diagnosis, i.e. define pathological phenotypes, and facilitate the monitoring of disease and therapy, and also, unravel underlying molecular pathways. Biomarker studies can either select predefined biomarker(s) measured by specific methods or apply an "unbiased" approach involving detection platforms that are indiscriminate in focus. This article reviews the technologies presently available to study biomarkers of lung disease within the 'omics field. The contributions of the individual 'omics analytical platforms to the field of respiratory diseases are summarised, with the goal of providing background on their respective abilities to contribute to systems medicine-based studies of lung disease.

Published
2013

38. Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk

Author

Dunlop, MG, Dobbins, SE, Farrington, SM, Jones, AM, Palles, C, Whiffin, N, Tenesa, A, Spain, S, Broderick, P, Ooi, L-Y, Domingo, E, Smillie, C, Henrion, M, Frampton, M, Martin, L, Grimes, G, Gorman, M, Semple, C, Ma, YP, Barclay, E, Prendergast, J, Cazier, J-B, Olver, B, Penegar, S, Lubbe, S, Chander, I, Carvajal-Carmona, LG, Ballereau, S, Lloyd, A, Vijayakrishnan, J, Zgaga, L, Rudan, I, Theodoratou, E, Starr, JM, Deary, I, Kirac, I, Kovacevic, D, Aaltonen, LA, Renkonen-Sinisalo, L, Mecklin, J-P, Matsuda, K, Nakamura, Y, Okada, Y, Gallinger, S, Duggan, DJ, Conti, D, Newcomb, P, Hopper, J, Jenkins, MA, Schumacher, F, Casey, G, Easton, D, Shah, M, Pharoah, P, Lindblom, A, Liu, T, Smith, CG, West, H, Cheadle, JP, Midgley, R, Kerr, DJ, Campbell, H, Tomlinson, IP, Houlston, RS, Dunlop, MG, Dobbins, SE, Farrington, SM, Jones, AM, Palles, C, Whiffin, N, Tenesa, A, Spain, S, Broderick, P, Ooi, L-Y, Domingo, E, Smillie, C, Henrion, M, Frampton, M, Martin, L, Grimes, G, Gorman, M, Semple, C, Ma, YP, Barclay, E, Prendergast, J, Cazier, J-B, Olver, B, Penegar, S, Lubbe, S, Chander, I, Carvajal-Carmona, LG, Ballereau, S, Lloyd, A, Vijayakrishnan, J, Zgaga, L, Rudan, I, Theodoratou, E, Starr, JM, Deary, I, Kirac, I, Kovacevic, D, Aaltonen, LA, Renkonen-Sinisalo, L, Mecklin, J-P, Matsuda, K, Nakamura, Y, Okada, Y, Gallinger, S, Duggan, DJ, Conti, D, Newcomb, P, Hopper, J, Jenkins, MA, Schumacher, F, Casey, G, Easton, D, Shah, M, Pharoah, P, Lindblom, A, Liu, T, Smith, CG, West, H, Cheadle, JP, Midgley, R, Kerr, DJ, Campbell, H, Tomlinson, IP, and Houlston, RS

Abstract

We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.

Published
2012

39. Multiple Common Susceptibility Variants near BMP Pathway Loci GREM1, BMP4, and BMP2 Explain Part of the Missing Heritability of Colorectal Cancer

Author

Gibson, G, Tomlinson, IPM, Carvajal-Carmona, LG, Dobbins, SE, Tenesa, A, Jones, AM, Howarth, K, Palles, C, Broderick, P, Jaeger, EEM, Farrington, S, Lewis, A, Prendergast, JGD, Pittman, AM, Theodoratou, E, Olver, B, Walker, M, Penegar, S, Barclay, E, Whiffin, N, Martin, L, Ballereau, S, Lloyd, A, Gorman, M, Lubbe, S, Howie, B, Marchini, J, Ruiz-Ponte, C, Fernandez-Rozadilla, C, Castells, A, Carracedo, A, Castellvi-Bel, S, Duggan, D, Conti, D, Cazier, J-B, Campbell, H, Sieber, O, Lipton, L, Gibbs, P, Martin, NG, Montgomery, GW, Young, J, Baird, PN, Gallinger, S, Newcomb, P, Hopper, J, Jenkins, MA, Aaltonen, LA, Kerr, DJ, Cheadle, J, Pharoah, P, Casey, G, Houlston, RS, Dunlop, MG, Gibson, G, Tomlinson, IPM, Carvajal-Carmona, LG, Dobbins, SE, Tenesa, A, Jones, AM, Howarth, K, Palles, C, Broderick, P, Jaeger, EEM, Farrington, S, Lewis, A, Prendergast, JGD, Pittman, AM, Theodoratou, E, Olver, B, Walker, M, Penegar, S, Barclay, E, Whiffin, N, Martin, L, Ballereau, S, Lloyd, A, Gorman, M, Lubbe, S, Howie, B, Marchini, J, Ruiz-Ponte, C, Fernandez-Rozadilla, C, Castells, A, Carracedo, A, Castellvi-Bel, S, Duggan, D, Conti, D, Cazier, J-B, Campbell, H, Sieber, O, Lipton, L, Gibbs, P, Martin, NG, Montgomery, GW, Young, J, Baird, PN, Gallinger, S, Newcomb, P, Hopper, J, Jenkins, MA, Aaltonen, LA, Kerr, DJ, Cheadle, J, Pharoah, P, Casey, G, Houlston, RS, and Dunlop, MG

Abstract

Genome-wide association studies (GWAS) have identified 14 tagging single nucleotide polymorphisms (tagSNPs) that are associated with the risk of colorectal cancer (CRC), and several of these tagSNPs are near bone morphogenetic protein (BMP) pathway loci. The penalty of multiple testing implicit in GWAS increases the attraction of complementary approaches for disease gene discovery, including candidate gene- or pathway-based analyses. The strongest candidate loci for additional predisposition SNPs are arguably those already known both to have functional relevance and to be involved in disease risk. To investigate this proposition, we searched for novel CRC susceptibility variants close to the BMP pathway genes GREM1 (15q13.3), BMP4 (14q22.2), and BMP2 (20p12.3) using sample sets totalling 24,910 CRC cases and 26,275 controls. We identified new, independent CRC predisposition SNPs close to BMP4 (rs1957636, P = 3.93×10(-10)) and BMP2 (rs4813802, P = 4.65×10(-11)). Near GREM1, we found using fine-mapping that the previously-identified association between tagSNP rs4779584 and CRC actually resulted from two independent signals represented by rs16969681 (P = 5.33×10(-8)) and rs11632715 (P = 2.30×10(-10)). As low-penetrance predisposition variants become harder to identify-owing to small effect sizes and/or low risk allele frequencies-approaches based on informed candidate gene selection may become increasingly attractive. Our data emphasise that genetic fine-mapping studies can deconvolute associations that have arisen owing to independent correlation of a tagSNP with more than one functional SNP, thus explaining some of the apparently missing heritability of common diseases.

Published
2011

40. TERCpolymorphisms are associated both with susceptibility to colorectal cancer and with longer telomeres

Author

Jones, A M, primary, Beggs, A D, additional, Carvajal-Carmona, L, additional, Farrington, S, additional, Tenesa, A, additional, Walker, M, additional, Howarth, K, additional, Ballereau, S, additional, Hodgson, S V, additional, Zauber, A, additional, Bertagnolli, M, additional, Midgley, R, additional, Campbell, H, additional, Kerr, D, additional, Dunlop, M G, additional, and Tomlinson, I P M, additional

Published
2011
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42. Thrust Oscillations in Solid Rocket Motors

Author

Guery, J., primary, Godfroy, F., additional, Ballereau, S., additional, Gallier, S., additional, Della Pieta, P., additional, Orlandi, O., additional, Robert, Eric, additional, and Cesco, Nathalie, additional

Published
2008
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48. Synthesis, Acid−Base Behavior, and Binding Properties of 6-Modified myo-Inositol 1,4,5-Tris(phosphate)s

Author

Ballereau, S., Guedat, P., Poirier, S. N., Guillemette, G., Spiess, B., and Schlewer, G.

Abstract

myo-Inositol 1,4,5-tris(phosphate) was modified at position 6. The analogues synthesized are reported in this publication are 6-deoxy-myo-inositol 1,4,5-tris(phosphate), 6-fluoro-6-deoxy-myo-inositol 1,4,5-tris(phosphate), epi-inositol 1,4,5-tris(phosphate), and 6-amino-6-deoxy-myo-inositol 1,4,5-tris(phosphate). These derivatives showed poor affinity for the Ins(1,4,5)P3 receptors. The inframolecular acid−base behavior and the cooperative effects between the phosphate groups could help explain the loss of affinity of these 6-modified analogues.

Published
1999

49. Synthesis, Calcium Mobilizing, and Physicochemical Properties of <SCP>d</SCP>-chiro-Inositol 1,3,4,6-Tetrakisphosphate, a Novel and Potent Ligand at the <SCP>d</SCP>-myo-Inositol 1,4,5-Trisphosphate Receptor

Author

Liu, C., Davis, R. J., Nahorski, S. R., Ballereau, S., Spiess, B., and Potter, B. V. L.

Abstract

The synthesis of a novel and potent ligand at the d-myo-inositol 1,4,5-trisphosphate receptor (InsP3R) is described. d-chiro-Inositol 1,3,4,6-tetrakisphosphate (7) and l-chiro-inositol 1,3,4,6-tetrakisphosphate (ent-7) have been synthesized from d-2,5-di-O-benzyl-chiro-inositol and l-2,5-di-O-benzyl-chiro-inositol, respectively. The potency of binding and Ca2+ release of 7 and ent-7 were examined in L15 and Lvec cells. 7 was a full agonist at the InsP3R in both cells, and ent-7 was inactive. The results are compared to those from d-myo-inositol 1,4,5-trisphosphate (1), dl-scyllo-inositol 1,2,4-trisphosphate (2), dl-myo-inositol 1,2,4,5-tetrakisphosphate (3), scyllo-inositol 1,2,4,5-tetrakisphosphate (4), d-myo-inositol 2,4,5-trisphosphate (5), and d-chiro-inositol 1,3,4-trisphosphate (6). The protonation processes of 7 have also been investigated by 31P NMR titration experiments.

Published
1999

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