Author: "Jose M G Izarzugaza" / Topic: genetics - Searchworks@Jio Institute Digital Library Search Results

24 results on '"Jose M G Izarzugaza"'

1. Correction: Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease.

Author: Enrique Audain, Anna Wilsdon, Jeroen Breckpot, Jose M G Izarzugaza, Tomas W Fitzgerald, Anne-Karin Kahlert, Alejandro Sifrim, Florian Wünnemann, Yasset Perez-Riverol, Hashim Abdul-Khaliq, Mads Bak, Anne S Bassett, D Woodrow Benson, Felix Berger, Ingo Daehnert, Koenraad Devriendt, Sven Dittrich, Piers Ef Daubeney, Vidu Garg, Karl Hackmann, Kirstin Hoff, Philipp Hofmann, Gregor Dombrowsky, Thomas Pickardt, Ulrike Bauer, Bernard D Keavney, Sabine Klaassen, Hans-Heiner Kramer, Christian R Marshall, Dianna M Milewicz, Scott Lemaire, Joseph S Coselli, Michael E Mitchell, Aoy Tomita-Mitchell, Siddharth K Prakash, Karl Stamm, Alexandre F R Stewart, Candice K Silversides, Reiner Siebert, Brigitte Stiller, Jill A Rosenfeld, Inga Vater, Alex V Postma, Almuth Caliebe, J David Brook, Gregor Andelfinger, Matthew E Hurles, Bernard Thienpont, Lars Allan Larsen, and Marc-Phillip Hitz
Subjects: Genetics, QH426-470
Abstract: [This corrects the article DOI: 10.1371/journal.pgen.1009679.].
Published: 2021
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2. Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease.

Author: Enrique Audain, Anna Wilsdon, Jeroen Breckpot, Jose M G Izarzugaza, Tomas W Fitzgerald, Anne-Karin Kahlert, Alejandro Sifrim, Florian Wünnemann, Yasset Perez-Riverol, Hashim Abdul-Khaliq, Mads Bak, Anne S Bassett, D Woodrow Benson, Felix Berger, Ingo Daehnert, Koenraad Devriendt, Sven Dittrich, Piers Ef Daubeney, Vidu Garg, Karl Hackmann, Kirstin Hoff, Philipp Hofmann, Gregor Dombrowsky, Thomas Pickardt, Ulrike Bauer, Bernard D Keavney, Sabine Klaassen, Hans-Heiner Kramer, Christian R Marshall, Dianna M Milewicz, Scott Lemaire, Joseph S Coselli, Michael E Mitchell, Aoy Tomita-Mitchell, Siddharth K Prakash, Karl Stamm, Alexandre F R Stewart, Candice K Silversides, Reiner Siebert, Brigitte Stiller, Jill A Rosenfeld, Inga Vater, Alex V Postma, Almuth Caliebe, J David Brook, Gregor Andelfinger, Matthew E Hurles, Bernard Thienpont, Lars Allan Larsen, and Marc-Phillip Hitz
Subjects: Genetics, QH426-470
Abstract: Numerous genetic studies have established a role for rare genomic variants in Congenital Heart Disease (CHD) at the copy number variation (CNV) and de novo variant (DNV) level. To identify novel haploinsufficient CHD disease genes, we performed an integrative analysis of CNVs and DNVs identified in probands with CHD including cases with sporadic thoracic aortic aneurysm. We assembled CNV data from 7,958 cases and 14,082 controls and performed a gene-wise analysis of the burden of rare genomic deletions in cases versus controls. In addition, we performed variation rate testing for DNVs identified in 2,489 parent-offspring trios. Our analysis revealed 21 genes which were significantly affected by rare CNVs and/or DNVs in probands. Fourteen of these genes have previously been associated with CHD while the remaining genes (FEZ1, MYO16, ARID1B, NALCN, WAC, KDM5B and WHSC1) have only been associated in small cases series or show new associations with CHD. In addition, a systems level analysis revealed affected protein-protein interaction networks involved in Notch signaling pathway, heart morphogenesis, DNA repair and cilia/centrosome function. Taken together, this approach highlights the importance of re-analyzing existing datasets to strengthen disease association and identify novel disease genes and pathways.
Published: 2021
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3. Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease

Author: Gregor Dombrowsky, Marc-Phillip Hitz, Hashim Abdul-Khaliq, Felix Berger, Piers E.F. Daubeney, Ingo Daehnert, Lars Allan Larsen, Michael E. Mitchell, Bernard Keavney, Mads Bak, Dianna M. Milewicz, Sven Dittrich, Philipp Hofmann, Kirstin Hoff, Woody D Benson, Hans-Heiner Kramer, Sabine Klaassen, Karl Hackmann, Siddharth K. Prakash, Brigitte Stiller, Aoy Tomita-Mitchell, Florian Wuennemann, Inga Vater, Christian R. Marshall, Anna Wilsdon, Alejandro Sifrim, Reiner Siebert, Thomas Pickardt, Scott Lemaire, Koenraad Devriendt, Joe Coselli, Almuth Caliebe, Enrique Audain, Karl Stamm, Kahlert Anne-Karin, Tomas W Fitzgerald, Jill A. Rosenfeld, Matthew E. Hurles, Alex V. Postma, Candice K. Silversides, Yasset Perez-Riverol, Jeroen Breckpot, John W. Belmont, U.M.M. Bauer, Gregor Andelfinger, Anne S. Bassett, Vidu Garg, Alexandre F.R. Stewart, David Brook, Bernard Thienpont, and Jose M. G. Izarzugaza
Subjects: Proband, Genetics, Heart morphogenesis, Mutation rate, Heart disease, DNA repair, Cardiovascular and Metabolic Diseases, medicine, Copy-number variation, Biology, Haploinsufficiency, medicine.disease, Gene
Abstract: Congenital Heart Disease (CHD) affects approximately 7-9 children per 1000 live births. Numerous genetic studies have established a role for rare genomic variants at the copy number variation (CNV) and single nucleotide variant level. In particular, the role of de novo mutations (DNM) has been highlighted in syndromic and non-syndromic CHD. To identify novel haploinsufficient CHD disease genes we performed an integrative analysis of CNVs and DNMs identified in probands with CHD including cases with sporadic thoracic aortic aneurysm (TAA). We assembled CNV data from 7,958 cases and 14,082 controls and performed a gene-wise analysis of the burden of rare genomic deletions in cases versus controls. In addition, we performed mutation rate testing for DNMs identified in 2,489 parent-offspring trios. Our combined analysis revealed 21 genes which were significantly affected by rare genomic deletions and/or constrained non-synonymous de novo mutations in probands. Fourteen of these genes have previously been associated with CHD while the remaining genes (FEZ1, MYO16, ARID1B, NALCN, WAC, KDM5B and WHSC1) have only been associated in singletons and small cases series, or show new associations with CHD. In addition, a systems level analysis revealed shared contribution of CNV deletions and DNMs in CHD probands, affecting protein-protein interaction networks involved in Notch signaling pathway, heart morphogenesis, DNA repair and cilia/centrosome function. Taken together, this approach highlights the importance of re-analyzing existing datasets to strengthen disease association and identify novel disease genes.
Published: 2020

4. Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Author: Bailey, Matthew H, Meyerson, William U, Dursi, Lewis Jonathan, Wang, Liang-Bo, Dong, Guanlan, Liang, Wen-Wei, Weerasinghe, Amila, Shantao, Li, Kelso, Sean, Saksena, Gordon, Ellrott, Kyle, Wendl, Michael C, Wheeler, David A, Getz, Gad, Simpson, Jared T, Gerstein, Mark B, Ding, Lirehan, Akbani, Pavana, Anur, Matthew, H Bailey, Alex, Buchanan, Kami, Chiotti, Kyle, Covington, Allison, Creason, Ding, Li, Kyle, Ellrott, Fan, Yu, Steven, Foltz, Gad, Getz, Walker, Hale, David, Haussler, Julian, M Hess, Carolyn, M Hutter, Cyriac, Kandoth, Katayoon, Kasaian, Melpomeni, Kasapi, Dave, Larson, Ignaty, Leshchiner, John, Letaw, Singer, Ma, Michael, D McLellan, Yifei, Men, Gordon, B Mills, Beifang, Niu, Myron, Peto, Amie, Radenbaugh, Sheila, M Reynolds, Gordon, Saksena, Heidi, Sofia, Chip, Stewart, Adam, J Struck, Joshua, M Stuart, Wenyi, Wang, John, N Weinstein, David, A Wheeler, Christopher, K Wong, Liu, Xi, Kai, Ye, Matthias, Bieg, Paul, C Boutros, Ivo, Buchhalter, Adam, P Butler, Ken, Chen, Zechen, Chong, Oliver, Drechsel, Lewis Jonathan Dursi, Roland, Eils, Shadrielle M, G Espiritu, Robert, S Fulton, Shengjie, Gao, Josep L, L Gelpi, Mark, B Gerstein, Santiago, Gonzalez, Ivo, G Gut, Faraz, Hach, Michael, C Heinold, Jonathan, Hinton, Taobo, Hu, Vincent, Huang, Huang, Yi, Barbara, Hutter, David, R Jones, Jongsun, Jung, Natalie, Jäger, Hyung-Lae, Kim, Kortine, Kleinheinz, Sushant, Kumar, Yogesh, Kumar, Christopher, M Lalansingh, Ivica, Letunic, Dimitri, Livitz, Eric, Z Ma, Yosef, E Maruvka, R Jay Mashl, Andrew, Menzies, Ana, Milovanovic, Morten Muhlig Nielsen, Stephan, Ossowski, Nagarajan, Paramasivam, Jakob Skou Pedersen, Marc, D Perry, Montserrat, Puiggròs, Keiran, M Raine, Esther, Rheinbay, Romina, Royo, S Cenk Sahinalp, Iman, Sarrafi, Matthias, Schlesner, Jared, T Simpson, Lucy, Stebbings, Miranda, D Stobbe, Jon, W Teague, Grace, Tiao, David, Torrents, Jeremiah, A Wala, Jiayin, Wang, Sebastian, M Waszak, Joachim, Weischenfeldt, Michael, C Wendl, Johannes, Werner, Zhenggang, Wu, Hong, Xue, Sergei, Yakneen, Takafumi, N Yamaguchi, Venkata, D Yellapantula, Christina, K Yung, Junjun, Zhang, Lauri, A Aaltonen, Federico, Abascal, Adam, Abeshouse, Hiroyuki, Aburatani, David, J Adams, Nishant, Agrawal, Keun Soo Ahn, Sung-Min, Ahn, Hiroshi, Aikata, Rehan, Akbani, Kadir, C Akdemir, Hikmat, Al-Ahmadie, Sultan, T Al-Sedairy, Fatima, Al-Shahrour, Malik, Alawi, Monique, Albert, Kenneth, Aldape, Ludmil, B Alexandrov, Adrian, Ally, Kathryn, Alsop, Eva, G Alvarez, Fernanda, Amary, Samirkumar, B Amin, Brice, Aminou, Ole, Ammerpohl, Matthew, J Anderson, Yeng, Ang, Davide, Antonello, Samuel, Aparicio, Elizabeth, L Appelbaum, Yasuhito, Arai, Axel, Aretz, Koji, Arihiro, Shun-Ichi, Ariizumi, Joshua, Armenia, Laurent, Arnould, Sylvia, Asa, Yassen, Assenov, Gurnit, Atwal, Sietse, Aukema, J Todd Auman, Miriam, R Aure, Philip, Awadalla, Marta, Aymerich, Gary, D Bader, Adrian, Baez-Ortega, Peter, J Bailey, Miruna, Balasundaram, Saianand, Balu, Pratiti, Bandopadhayay, Rosamonde, E Banks, Stefano, Barbi, Andrew, P Barbour, Jonathan, Barenboim, Jill, Barnholtz-Sloan, Hugh, Barr, Elisabet, Barrera, John, Bartlett, Javier, Bartolome, Bassi, Claudio, Oliver, F Bathe, Daniel, Baumhoer, Prashant, Bavi, Stephen, B Baylin, Wojciech, Bazant, Duncan, Beardsmore, Timothy, A Beck, Sam, Behjati, Andreas, Behren, Cindy, Bell, Sergi, Beltran, Christopher, Benz, Andrew, Berchuck, Anke, K Bergmann, Erik, N Bergstrom, Benjamin, P Berman, Daniel, M Berney, Stephan, H Bernhart, Rameen, Beroukhim, Mario, Berrios, Samantha, Bersani, Johanna, Bertl, Miguel, Betancourt, Vinayak, Bhandari, Shriram, G Bhosle, Andrew, V Biankin, Darell, Bigner, Hans, Binder, Ewan, Birney, Michael, Birrer, Nidhan, K Biswas, Bodil, Bjerkehagen, Tom, Bodenheimer, Lori, Boice, Giada, Bonizzato, Johann, S De Bono, Arnoud, Boot, Moiz, S Bootwalla, Ake, Borg, Arndt, Borkhardt, Keith, A Boroevich, Ivan, Borozan, Christoph, Borst, Marcus, Bosenberg, Mattia, Bosio, Jacqueline, Boultwood, Guillaume, Bourque, G Steven Bova, David, T Bowen, Reanne, Bowlby, David D, L Bowtell, Sandrine, Boyault, Rich, Boyce, Jeffrey, Boyd, Alvis, Brazma, Paul, Brennan, Daniel, S Brewer, Arie, B Brinkman, Robert, G Bristow, Russell, R Broaddus, Jane, E Brock, Malcolm, Brock, Annegien, Broeks, Angela, N Brooks, Denise, Brooks, Benedikt, Brors, Søren, Brunak, Timothy J, C Bruxner, Alicia, L Bruzos, Christiane, Buchholz, Susan, Bullman, Hazel, Burke, Birgit, Burkhardt, Kathleen, H Burns, John, Busanovich, Carlos, D Bustamante, Atul, J Butte, Niall, J Byrne, Anne-Lise, Børresen-Dale, Samantha, J Caesar-Johnson, Andy, Cafferkey, Declan, Cahill, Claudia, Calabrese, Carlos, Caldas, Fabien, Calvo, Niedzica, Camacho, Peter, J Campbell, Elias, Campo, Cinzia, Cantù, Shaolong, Cao, Thomas, E Carey, Joana, Carlevaro-Fita, Rebecca, Carlsen, Ivana, Cataldo, Mario, Cazzola, Jonathan, Cebon, Robert, Cerfolio, Dianne, E Chadwick, Dimple, Chakravarty, Don, Chalmers, Calvin Wing Yiu Chan, Kin, Chan, Michelle, Chan-Seng-Yue, Vishal, S Chandan, David, K Chang, Stephen, J Chanock, Lorraine, A Chantrill, Aurélien, Chateigner, Nilanjan, Chatterjee, Kazuaki, Chayama, Hsiao-Wei, Chen, Jieming, Chen, Yiwen, Chen, Zhaohong, Chen, Andrew, D Cherniack, Jeremy, Chien, Yoke-Eng, Chiew, Suet-Feung, Chin, Juok, Cho, Sunghoon, Cho, Jung Kyoon Choi, Wan, Choi, Christine, Chomienne, Su Pin Choo, Angela, Chou, Angelika, N Christ, Elizabeth, L Christie, Eric, Chuah, Carrie, Cibulskis, Kristian, Cibulskis, Sara, Cingarlini, Peter, Clapham, Alexander, Claviez, Sean, Cleary, Nicole, Cloonan, Marek, Cmero, Colin, C Collins, Ashton, A Connor, Susanna, L Cooke, Colin, S Cooper, Leslie, Cope, Corbo, Vincenzo, Matthew, G Cordes, Stephen, M Cordner, Isidro, Cortés-Ciriano, Prue, A Cowin, Brian, Craft, David, Craft, Chad, J Creighton, Yupeng, Cun, Erin, Curley, Ioana, Cutcutache, Karolina, Czajka, Bogdan, Czerniak, Rebecca, A Dagg, Ludmila, Danilova, Maria Vittoria Davi, Natalie, R Davidson, Helen, Davies, Ian, J Davis, Brandi, N Davis-Dusenbery, Kevin, J Dawson, Francisco, M De La Vega, Ricardo De Paoli-Iseppi, Timothy, Defreitas, Angelo, P Dei Tos, Olivier, Delaneau, John, A Demchok, Jonas, Demeulemeester, German, M Demidov, Deniz, Demircioğlu, Nening, M Dennis, Robert, E Denroche, Stefan, C Dentro, Nikita, Desai, Vikram, Deshpande, Amit, G Deshwar, Christine, Desmedt, Jordi, Deu-Pons, Noreen, Dhalla, Neesha, C Dhani, Priyanka, Dhingra, Rajiv, Dhir, Anthony, Dibiase, Klev, Diamanti, Shuai, Ding, Huy, Q Dinh, Luc, Dirix, Harshavardhan, Doddapaneni, Nilgun, Donmez, Michelle, T Dow, Ronny, Drapkin, Ruben, M Drews, Serge, Serge, Tim, Dudderidge, Ana, Dueso-Barroso, Andrew, J Dunford, Michael, Dunn, Fraser, R Duthie, Ken, Dutton-Regester, Jenna, Eagles, Douglas, F Easton, Stuart, Edmonds, Paul, A Edwards, Sandra, E Edwards, Rosalind, A Eeles, Anna, Ehinger, Juergen, Eils, Adel, El-Naggar, Matthew, Eldridge, Serap, Erkek, Georgia, Escaramis, Xavier, Estivill, Dariush, Etemadmoghadam, Jorunn, E Eyfjord, Bishoy, M Faltas, Daiming, Fan, William, C Faquin, Claudiu, Farcas, Matteo, Fassan, Aquila, Fatima, Francesco, Favero, Nodirjon, Fayzullaev, Ina, Felau, Sian, Fereday, Martin, L Ferguson, Vincent, Ferretti, Lars, Feuerbach, Matthew, A Field, J Lynn Fink, Gaetano, Finocchiaro, Cyril, Fisher, Matthew, W Fittall, Anna, Fitzgerald, Rebecca, C Fitzgerald, Adrienne, M Flanagan, Neil, E Fleshner, Paul, Flicek, John, A Foekens, Kwun, M Fong, Nuno, A Fonseca, Christopher, S Foster, Natalie, S Fox, Michael, Fraser, Scott, Frazer, Milana, Frenkel-Morgenstern, William, Friedman, Joan, Frigola, Catrina, C Fronick, Akihiro, Fujimoto, Masashi, Fujita, Masashi, Fukayama, Lucinda, A Fulton, Mayuko, Furuta, P Andrew Futreal, Anja, Füllgrabe, Stacey, B Gabriel, Steven, Gallinger, Carlo, Gambacorti-Passerini, Jianjiong, Gao, Levi, Garraway, Øystein, Garred, Erik, Garrison, Dale, W Garsed, Nils, Gehlenborg, Joshy, George, Daniela, S Gerhard, Clarissa, Gerhauser, Jeffrey, E Gershenwald, Moritz, Gerstung, Mohammed, Ghori, Ronald, Ghossein, Nasra, H Giama, Richard, A Gibbs, Anthony, J Gill, Pelvender, Gill, Dilip, D Giri, Dominik, Glodzik, Vincent, J Gnanapragasam, Maria Elisabeth Goebler, Mary, J Goldman, Carmen, Gomez, Abel, Gonzalez-Perez, Dmitry, A Gordenin, James, Gossage, Kunihito, Gotoh, Ramaswamy, Govindan, Dorthe, Grabau, Janet, S Graham, Robert, C Grant, Anthony, R Green, Eric, Green, Liliana, Greger, Nicola, Grehan, Sonia, Grimaldi, Sean, M Grimmond, Robert, L Grossman, Adam, Grundhoff, Gunes, Gundem, Qianyun, Guo, Manaswi, Gupta, Shailja, Gupta, Marta, Gut, Jonathan, Göke, Gavin, Ha, Andrea, Haake, David, Haan, Siegfried, Haas, Kerstin, Haase, James, E Haber, Nina, Habermann, Syed, Haider, Natsuko, Hama, Freddie, C Hamdy, Anne, Hamilton, Mark, P Hamilton, Leng, Han, George, B Hanna, Martin, Hansmann, Nicholas, J Haradhvala, Olivier, Harismendy, Ivon, Harliwong, Arif, O Harmanci, Eoghan, Harrington, Takanori, Hasegawa, Steve, Hawkins, Shinya, Hayami, Shuto, Hayashi, D Neil Hayes, Stephen, J Hayes, Nicholas, K Hayward, Steven, Hazell, Yao, He, Allison, P Heath, Simon, C Heath, David, Hedley, Apurva, M Hegde, David, I Heiman, Zachary, Heins, Lawrence, E Heisler, Eva, Hellstrom-Lindberg, Mohamed, Helmy, Seong Gu Heo, Austin, J Hepperla, José María Heredia-Genestar, Carl, Herrmann, Peter, Hersey, Holmfridur, Hilmarsdottir, Satoshi, Hirano, Nobuyoshi, Hiraoka, Katherine, A Hoadley, Asger, Hobolth, Ermin, Hodzic, Jessica, I Hoell, Steve, Hoffmann, Oliver, Hofmann, Andrea, Holbrook, Aliaksei, Z Holik, Michael, A Hollingsworth, Oliver, Holmes, Robert, A Holt, Chen, Hong, Eun Pyo Hong, Jongwhi, H Hong, Gerrit, K Hooijer, Henrik, Hornshøj, Fumie, Hosoda, Yong, Hou, Volker, Hovestadt, William, Howat, Alan, P Hoyle, Ralph, H Hruban, Jianhong, Hu, Xing, Hua, Kuan-Lin, Huang, Mei, Huang, Mi Ni Huang, Wolfgang, Huber, Thomas, J Hudson, Michael, Hummel, Jillian, A Hung, David, Huntsman, Ted, R Hupp, Jason, Huse, Matthew, R Huska, Daniel, Hübschmann, Christine, A Iacobuzio-Donahue, Charles David Imbusch, Marcin, Imielinski, Seiya, Imoto, William, B Isaacs, Keren, Isaev, Shumpei, Ishikawa, Murat, Iskar, M Ashiqul Islam, S, Michael, Ittmann, Sinisa, Ivkovic, Jose M, G Izarzugaza, Jocelyne, Jacquemier, Valerie, Jakrot, Nigel, B Jamieson, Gun Ho Jang, Se Jin Jang, Joy, C Jayaseelan, Reyka, Jayasinghe, Stuart, R Jefferys, Karine, Jegalian, Jennifer, L Jennings, Seung-Hyup, Jeon, Lara, Jerman, Yuan, Ji, Wei, Jiao, Peter, A Johansson, Amber, L Johns, Jeremy, Johns, Rory, Johnson, Todd, A Johnson, Clemency, Jolly, Yann, Joly, Jon, G Jonasson, Corbin, D Jones, David T, W Jones, Nic, Jones, Steven J, M Jones, Jos, Jonkers, Young Seok Ju, Hartmut, Juhl, Malene, Juul, Randi Istrup Juul, Sissel, Juul, Rolf, Kabbe, Andre, Kahles, Abdullah, Kahraman, Vera, B Kaiser, Hojabr, Kakavand, Sangeetha, Kalimuthu, Christof von Kalle, Koo Jeong Kang, Katalin, Karaszi, Beth, Karlan, Rosa, Karlić, Dennis, Karsch, Karin, S Kassahn, Hitoshi, Katai, Mamoru, Kato, Hiroto, Katoh, Yoshiiku, Kawakami, Jonathan, D Kay, Stephen, H Kazakoff, Marat, D Kazanov, Maria, Keays, Electron, Kebebew, Richard, F Kefford, Manolis, Kellis, James, G Kench, Catherine, J Kennedy, Jules N, A Kerssemakers, David, Khoo, Vincent, Khoo, Narong, Khuntikeo, Ekta, Khurana, Helena, Kilpinen, Hark Kyun Kim, Hyung-Yong, Kim, Hyunghwan, Kim, Jaegil, Kim, Jihoon, Kim, Jong, K Kim, Youngwook, Kim, Tari, A King, Wolfram, Klapper, Leszek, J Klimczak, Stian, Knappskog, Michael, Kneba, Bartha, M Knoppers, Youngil, Koh, Jan, Komorowski, Daisuke, Komura, Mitsuhiro, Komura, Kong, Gu, Marcel, Kool, Jan, O Korbel, Viktoriya, Korchina, Andrey, Korshunov, Michael, Koscher, Roelof, Koster, Zsofia, Kote-Jarai, Antonios, Koures, Milena, Kovacevic, Barbara, Kremeyer, Helene, Kretzmer, Markus, Kreuz, Savitri, Krishnamurthy, Dieter, Kube, Kiran, Kumar, Pardeep, Kumar, Ritika, Kundra, Kirsten, Kübler, Ralf, Küppers, Jesper, Lagergren, Phillip, H Lai, Peter, W Laird, Sunil, R Lakhani, Emilie, Lalonde, Fabien, C Lamaze, Adam, Lambert, Eric, Lander, Pablo, Landgraf, Landoni, Luca, Anita, Langerød, Andrés, Lanzós, Denis, Larsimont, Erik, Larsson, Mark, Lathrop, Loretta M, S Lau, Chris, Lawerenz, Rita, T Lawlor, Michael, S Lawrence, Alexander, J Lazar, Xuan, Le, Darlene, Lee, Donghoon, Lee, Eunjung Alice Lee, Hee Jin Lee, Jake June-Koo Lee, Jeong-Yeon, Lee, Juhee, Lee, Ming Ta Michael Lee, Henry, Lee-Six, Kjong-Van, Lehmann, Hans, Lehrach, Dido, Lenze, Conrad, R Leonard, Daniel, A Leongamornlert, Louis, Letourneau, Douglas, A Levine, Lora, Lewis, Tim, Ley, Chang, Li, Constance, H Li, Haiyan Irene Li, Jun, Li, Lin, Li, Siliang, Li, Xiaobo, Li, Xiaotong, Li, Xinyue, Li, Yilong, Li, Han, Liang, Sheng-Ben, Liang, Peter, Lichter, Pei, Lin, Ziao, Lin, M Linehan, W, Ole Christian Lingjærde, Dongbing, Liu, Eric Minwei Liu, Fei-Fei, Liu, Fenglin, Liu, Jia, Liu, Xingmin, Liu, Julie, Livingstone, Naomi, Livni, Lucas, Lochovsky, Markus, Loeffler, Georgina, V Long, Armando, Lopez-Guillermo, Shaoke, Lou, David, N Louis, Laurence, B Lovat, Yiling, Lu, Yong-Jie, Lu, Youyong, Lu, Luchini, Claudio, Ilinca, Lungu, Xuemei, Luo, Hayley, J Luxton, Andy, G Lynch, Lisa, Lype, Cristina, López, Carlos, López-Otín, Yussanne, Ma, Gaetan, Macgrogan, Shona, Macrae, Geoff, Macintyre, Tobias, Madsen, Kazuhiro, Maejima, Andrea, Mafficini, Dennis, T Maglinte, Arindam, Maitra, Partha, P Majumder, Luca, Malcovati, Salem, Malikic, Malleo, Giuseppe, Graham, J Mann, Luisa, Mantovani-Löffler, Kathleen, Marchal, Giovanni, Marchegiani, Elaine, R Mardis, Adam, A Margolin, Maximillian, G Marin, Florian, Markowetz, Julia, Markowski, Jeffrey, Marks, Tomas, Marques-Bonet, Marco, A Marra, Luke, Marsden, John W, M Martens, Sancha, Martin, Jose, I Martin-Subero, Iñigo, Martincorena, Alexander, Martinez-Fundichely, Charlie, E Massie, Thomas, J Matthew, Lucy, Matthews, Erik, Mayer, Simon, Mayes, Michael, Mayo, Faridah, Mbabaali, Karen, Mccune, Ultan, Mcdermott, Patrick, D McGillivray, John, D McPherson, John, R McPherson, Treasa, A McPherson, Samuel, R Meier, Alice, Meng, Shaowu, Meng, Neil, D Merrett, Sue, Merson, Matthew, Meyerson, William, U Meyerson, Piotr, A Mieczkowski, George, L Mihaiescu, Sanja, Mijalkovic, Ana Mijalkovic Mijalkovic-Lazic, Tom, Mikkelsen, Milella, Michele, Linda, Mileshkin, Christopher, A Miller, David, K Miller, Jessica, K Miller, Sarah, Minner, Marco, Miotto, Gisela Mir Arnau, Lisa, Mirabello, Chris, Mitchell, Thomas, J Mitchell, Satoru, Miyano, Naoki, Miyoshi, Shinichi, Mizuno, Fruzsina, Molnár-Gábor, Malcolm, J Moore, Richard, A Moore, Sandro, Morganella, Quaid, D Morris, Carl, Morrison, Lisle, E Mose, Catherine, D Moser, Ferran, Muiños, Loris, Mularoni, Andrew, J Mungall, Karen, Mungall, Elizabeth, A Musgrove, Ville, Mustonen, David, Mutch, Francesc, Muyas, Donna, M Muzny, Alfonso, Muñoz, Jerome, Myers, Ola, Myklebost, Peter, Möller, Genta, Nagae, Adnan, M Nagrial, Hardeep, K Nahal-Bose, Hitoshi, Nakagama, Hidewaki, Nakagawa, Hiromi, Nakamura, Toru, Nakamura, Kaoru, Nakano, Tannistha, Nandi, Jyoti, Nangalia, Mia, Nastic, Arcadi, Navarro, Fabio C, P Navarro, David, E Neal, Gerd, Nettekoven, Felicity, Newell, Steven, J Newhouse, Yulia, Newton, Alvin Wei Tian Ng, Anthony, Ng, Jonathan, Nicholson, David, Nicol, Yongzhan, Nie, G Petur Nielsen, Serena, Nik-Zainal, Michael, S Noble, Katia, Nones, Paul, A Northcott, Faiyaz, Notta, Brian, D O'Connor, Peter, O'Donnell, Maria, O'Donovan, Sarah, O'Meara, Brian Patrick O'Neill, J Robert O'Neill, David, Ocana, Angelica, Ochoa, Layla, Oesper, Christopher, Ogden, Hideki, Ohdan, Kazuhiro, Ohi, Lucila, Ohno-Machado, Karin, A Oien, Akinyemi, I Ojesina, Hidenori, Ojima, Takuji, Okusaka, Larsson, Omberg, Choon Kiat Ong, German, Ott, F Francis Ouellette, B, Christine, P'Ng, Marta, Paczkowska, Paiella, Salvatore, Chawalit, Pairojkul, Marina, Pajic, Qiang, Pan-Hammarström, Elli, Papaemmanuil, Irene, Papatheodorou, Ji Wan Park, Joong-Won, Park, Keunchil, Park, Kiejung, Park, Peter, J Park, Joel, S Parker, Simon, L Parsons, Harvey, Pass, Danielle, Pasternack, Alessandro, Pastore, Ann-Marie, Patch, Iris, Pauporté, Antonio, Pea, John, V Pearson, Chandra Sekhar Pedamallu, Paolo, Pederzoli, Martin, Peifer, Nathan, A Pennell, Charles, M Perou, Gloria, M Petersen, Nicholas, Petrelli, Robert, Petryszak, Stefan, M Pfister, Mark, Phillips, Oriol, Pich, Hilda, A Pickett, Todd, D Pihl, Nischalan, Pillay, Sarah, Pinder, Mark, Pinese, Andreia, V Pinho, Esa, Pitkänen, Xavier, Pivot, Elena, Piñeiro-Yáñez, Laura, Planko, Christoph, Plass, Paz, Polak, Tirso, Pons, Irinel, Popescu, Olga, Potapova, Aparna, Prasad, Shaun, R Preston, Manuel, Prinz, Antonia, L Pritchard, Stephenie, D Prokopec, Elena, Provenzano, Xose, S Puente, Sonia, Puig, Sergio, Pulido-Tamayo, Gulietta, M Pupo, Colin, A Purdie, Michael, C Quinn, Raquel, Rabionet, Janet, S Rader, Bernhard, Radlwimmer, Petar, Radovic, Benjamin, Raeder, Manasa, Ramakrishna, Kamna, Ramakrishnan, Suresh, Ramalingam, Benjamin, J Raphael, W Kimryn Rathmell, Tobias, Rausch, Guido, Reifenberger, Jüri, Reimand, Jorge, Reis-Filho, Victor, Reuter, Iker, Reyes-Salazar, Matthew, A Reyna, Yasser, Riazalhosseini, Andrea, L Richardson, Julia, Richter, Matthew, Ringel, Markus, Ringnér, Yasushi, Rino, Karsten, Rippe, Jeffrey, Roach, Lewis, R Roberts, Nicola, D Roberts, Steven, A Roberts, A Gordon Robertson, Alan, J Robertson, Javier Bartolomé Rodriguez, Bernardo, Rodriguez-Martin, F Germán Rodríguez-González, Michael H, A Roehrl, Marius, Rohde, Hirofumi, Rokutan, Gilles, Romieu, Ilse, Rooman, Tom, Roques, Daniel, Rosebrock, Mara, Rosenberg, Philip, C Rosenstiel, Andreas, Rosenwald, Edward, W Rowe, Steven, G Rozen, Yulia, Rubanova, Mark, A Rubin, Carlota, Rubio-Perez, Vasilisa, A Rudneva, Borislav, C Rusev, Ruzzenente, Andrea, Gunnar, Rätsch, Radhakrishnan, Sabarinathan, Veronica, Y Sabelnykova, Sara, Sadeghi, Natalie, Saini, Mihoko, Saito-Adachi, Adriana, Salcedo, Roberto, Salgado, Leonidas, Salichos, Richard, Sallari, Charles, Saller, Salvia, Roberto, Michelle, Sam, Jaswinder, S Samra, Francisco, Sanchez-Vega, Chris, Sander, Grant, Sanders, Rajiv, Sarin, Aya, Sasaki-Oku, Torill, Sauer, Guido, Sauter, Robyn P, M Saw, Maria, Scardoni, Christopher, J Scarlett, Scarpa, Aldo, Ghislaine, Scelo, Dirk, Schadendorf, Jacqueline, E Schein, Markus, B Schilhabel, Thorsten, Schlomm, Heather, K Schmidt, Sarah-Jane, Schramm, Stefan, Schreiber, Nikolaus, Schultz, Steven, E Schumacher, Roland, F Schwarz, Richard, A Scolyer, David, Scott, Ralph, Scully, Raja, Seethala, Ayellet, V Segre, Iris, Selander, Colin, A Semple, Yasin, Senbabaoglu, Subhajit, Sengupta, Elisabetta, Sereni, Stefano, Serra, Dennis, C Sgroi, Mark, Shackleton, Nimish, C Shah, Sagedeh, Shahabi, Catherine, A Shang, Ping, Shang, Ofer, Shapira, Troy, Shelton, Ciyue, Shen, Hui, Shen, Rebecca, Shepherd, Ruian, Shi, Yan, Shi, Yu-Jia, Shiah, Tatsuhiro, Shibata, Juliann, Shih, Eigo, Shimizu, Kiyo, Shimizu, Seung Jun Shin, Yuichi, Shiraishi, Tal, Shmaya, Ilya, Shmulevich, Solomon, I Shorser, Charles, Short, Raunak, Shrestha, Suyash, S Shringarpure, Craig, Shriver, Shimin, Shuai, Nikos, Sidiropoulos, Reiner, Siebert, Anieta, M Sieuwerts, Lina, Sieverling, Sabina, Signoretti, Katarzyna, O Sikora, Michele, Simbolo, Ronald, Simon, Janae, V Simons, Peter, T Simpson, Samuel, Singer, Nasa, Sinnott-Armstrong, Payal, Sipahimalani, Tara, J Skelly, Marcel, Smid, Jaclyn, Smith, Karen, Smith-McCune, Nicholas, D Socci, Heidi, J Sofia, Matthew, G Soloway, Lei, Song, Anil, K Sood, Sharmila, Sothi, Christos, Sotiriou, Cameron, M Soulette, Paul, N Span, Paul, T Spellman, Sperandio, Nicola, Andrew, J Spillane, Oliver, Spiro, Jonathan, Spring, Johan, Staaf, Peter, F Stadler, Peter, Staib, Stefan, G Stark, Ólafur Andri Stefánsson, Oliver, Stegle, Lincoln, D Stein, Alasdair, Stenhouse, Stephan, Stilgenbauer, Michael, R Stratton, Jonathan, R Stretch, Henk, G Stunnenberg, Hong, Su, Xiaoping, Su, Ren, X Sun, Stephanie, Sungalee, Hana, Susak, Akihiro, Suzuki, Fred, Sweep, Monika, Szczepanowski, Holger, Sültmann, Takashi, Yugawa, Angela, Tam, David, Tamborero, Benita Kiat Tee Tan, Donghui, Tan, Patrick, Tan, Hiroko, Tanaka, Hirokazu, Taniguchi, Tomas, J Tanskanen, Maxime, Tarabichi, Roy, Tarnuzzer, Patrick, Tarpey, Morgan, L Taschuk, Kenji, Tatsuno, Simon, Tavaré, Darrin, F Taylor, Amaro, Taylor-Weiner, Bin Tean Teh, Varsha, Tembe, Javier, Temes, Kevin, Thai, Sarah, P Thayer, Nina, Thiessen, Gilles, Thomas, Sarah, Thomas, Alan, Thompson, Alastair, M Thompson, John, F Thompson, R Houston Thompson, Heather, Thorne, Leigh, B Thorne, Adrian, Thorogood, Nebojsa, Tijanic, Lee, E Timms, Roberto, Tirabosco, Marta, Tojo, Stefania, Tommasi, Christopher, W Toon, Umut, H Toprak, Giampaolo, Tortora, Jörg, Tost, Yasushi, Totoki, David, Townend, Nadia, Traficante, Isabelle, Treilleux, Jean-Rémi, Trotta, Lorenz H, P Trümper, Ming, Tsao, Tatsuhiko, Tsunoda, Jose M, C Tubio, Olga, Tucker, Richard, Turkington, Daniel, J Turner, Andrew, Tutt, Masaki, Ueno, Naoto, T Ueno, Christopher, Umbricht, Husen, M Umer, Timothy, J Underwood, Lara, Urban, Tomoko, Urushidate, Tetsuo, Ushiku, Liis, Uusküla-Reimand, Alfonso, Valencia, David, J Van Den Berg, Steven Van Laere, Peter Van Loo, Erwin, G Van Meir, Gert, G Van den Eynden, Theodorus Van der Kwast, Naveen, Vasudev, Miguel, Vazquez, Ravikiran, Vedururu, Umadevi, Veluvolu, Shankar, Vembu, Lieven P, C Verbeke, Peter, Vermeulen, Clare, Verrill, Alain, Viari, David, Vicente, Caterina, Vicentini, K Vijay Raghavan, Juris, Viksna, Ricardo, E Vilain, Izar, Villasante, Anne, Vincent-Salomon, Tapio, Visakorpi, Douglas, Voet, Paresh, Vyas, Ignacio, Vázquez-García, Nick, M Waddell, Nicola, Waddell, Claes, Wadelius, Lina, Wadi, Rabea, Wagener, Jian, Wang, Linghua, Wang, Wang, Qi, Yumeng, Wang, Zhining, Wang, Paul, M Waring, Hans-Jörg, Warnatz, Jonathan, Warrell, Anne, Y Warren, David, C Wedge, Dieter, Weichenhan, Paul, Weinberger, Daniel, J Weisenberger, Ian, Welch, Justin, P Whalley, Hayley, C Whitaker, Dennis, Wigle, Matthew, D Wilkerson, Ashley, Williams, James, S Wilmott, Gavin, W Wilson, Julie, M Wilson, Richard, K Wilson, Boris, Winterhoff, Jeffrey, A Wintersinger, Maciej, Wiznerowicz, Stephan, Wolf, Bernice, H Wong, Tina, Wong, Winghing, Wong, Youngchoon, Woo, Scott, Wood, Bradly, G Wouters, Adam, J Wright, Derek, W Wright, Mark, H Wright, Chin-Lee, Wu, Dai-Ying, Wu, Guanming, Wu, Jianmin, Wu, Kui, Wu, Yang, Wu, Tian, Xia, Qian, Xiang, Xiao, Xiao, Rui, Xing, Heng, Xiong, Qinying, Xu, Yanxun, Xu, Shinichi, Yachida, Rui, Yamaguchi, Masakazu, Yamamoto, Shogo, Yamamoto, Hiroki, Yamaue, Fan, Yang, Huanming, Yang, Jean, Y Yang, Liming, Yang, Lixing, Yang, Shanlin, Yang, Tsun-Po, Yang, Yang, Yang, Xiaotong, Yao, Marie-Laure, Yaspo, Lucy, Yates, Christina, Yau, Chen, Ye, Christopher, J Yoon, Sung-Soo, Yoon, Fouad, Yousif, Jun, Yu, Kaixian, Yu, Willie, Yu, Yingyan, Yu, Yuan, Ke, Yuan, Yuan, Denis, Yuen, Olga, Zaikova, Jorge, Zamora, Marc, Zapatka, Jean, C Zenklusen, Thorsten, Zenz, Nikolajs, Zeps, Cheng-Zhong, Zhang, Fan, Zhang, Hailei, Zhang, Hongwei, Zhang, Hongxin, Zhang, Jiashan, Zhang, Jing, Zhang, Xiuqing, Zhang, Xuanping, Zhang, Yan, Zhang, Zemin, Zhang, Zhongming, Zhao, Liangtao, Zheng, Xiuqing, Zheng, Wanding, Zhou, Yong, Zhou, Bin, Zhu, Hongtu, Zhu, Jingchun, Zhu, Shida, Zhu, Lihua, Zou, Xueqing, Zou, Anna, Defazio, Nicholas van As, Carolien H, M van Deurzen, Marc, J van de Vijver, L Van't Veer, Christian von Mering, Medical Oncology, Pathology, Bailey, Matthew H. [0000-0003-4526-9727], Dursi, Lewis Jonathan [0000-0002-4697-798X], Wang, Liang-Bo [0000-0001-6977-9348], Dong, Guanlan [0000-0002-4747-6036], Weerasinghe, Amila [0000-0003-3568-5823], Li, Shantao [0000-0002-5440-2780], Saksena, Gordon [0000-0001-6630-7935], Ellrott, Kyle [0000-0002-6573-5900], Wheeler, David A. [0000-0002-9056-6299], Getz, Gad [0000-0002-0936-0753], Gerstein, Mark B. [0000-0002-9746-3719], Apollo - University of Cambridge Repository, CCA - Cancer biology and immunology, Graduate School, Laboratory Genetic Metabolic Diseases, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, CCA -Cancer Center Amsterdam, Bailey, M, Meyerson, W, Dursi, L, Wang, L, Dong, G, Liang, W, Weerasinghe, A, Li, S, Kelso, S, Akbani, R, Anur, P, Buchanan, A, Chiotti, K, Covington, K, Creason, A, Ding, L, Ellrott, K, Fan, Y, Foltz, S, Getz, G, Hale, W, Haussler, D, Hess, J, Hutter, C, Kandoth, C, Kasaian, K, Kasapi, M, Larson, D, Leshchiner, I, Letaw, J, Ma, S, Mclellan, M, Men, Y, Mills, G, Niu, B, Peto, M, Radenbaugh, A, Reynolds, S, Saksena, G, Sofia, H, Stewart, C, Struck, A, Stuart, J, Wang, W, Weinstein, J, Wheeler, D, Wong, C, Xi, L, Ye, K, Bieg, M, Boutros, P, Buchhalter, I, Butler, A, Chen, K, Chong, Z, Drechsel, O, Jonathan Dursi, L, Eils, R, Espiritu, S, Fulton, R, Gao, S, Gelpi, J, Gerstein, M, Gonzalez, S, Gut, I, Hach, F, Heinold, M, Hinton, J, Hu, T, Huang, V, Huang, Y, Hutter, B, Jones, D, Jung, J, Jager, N, Kim, H, Kleinheinz, K, Kumar, S, Kumar, Y, Lalansingh, C, Letunic, I, Livitz, D, Ma, E, Maruvka, Y, Mashl, R, Menzies, A, Milovanovic, A, Nielsen, M, Ossowski, S, Paramasivam, N, Pedersen, J, Perry, M, Puiggros, M, Raine, K, Rheinbay, E, Royo, R, Sahinalp, S, Sarrafi, I, Schlesner, M, Simpson, J, Stebbings, L, Stobbe, M, Teague, J, Tiao, G, Torrents, D, Wala, J, Wang, J, Waszak, S, Weischenfeldt, J, Wendl, M, Werner, J, Wu, Z, Xue, H, Yakneen, S, Yamaguchi, T, Yellapantula, V, Yung, C, Zhang, J, Aaltonen, L, Abascal, F, Abeshouse, A, Aburatani, H, Adams, D, Agrawal, N, Ahn, K, Ahn, S, Aikata, H, Akdemir, K, Al-Ahmadie, H, Al-Sedairy, S, Al-Shahrour, F, Alawi, M, Albert, M, Aldape, K, Alexandrov, L, Ally, A, Alsop, K, Alvarez, E, Amary, F, Amin, S, Aminou, B, Ammerpohl, O, Anderson, M, Ang, Y, Antonello, D, Aparicio, S, Appelbaum, E, Arai, Y, Aretz, A, Arihiro, K, Ariizumi, S, Armenia, J, Arnould, L, Asa, S, Assenov, Y, Atwal, G, Aukema, S, Auman, J, Aure, M, Awadalla, P, Aymerich, M, Bader, G, Baez-Ortega, A, Bailey, P, Balasundaram, M, Balu, S, Bandopadhayay, P, Banks, R, Barbi, S, Barbour, A, Barenboim, J, Barnholtz-Sloan, J, Barr, H, Barrera, E, Bartlett, J, Bartolome, J, Bassi, C, Bathe, O, Baumhoer, D, Bavi, P, Baylin, S, Bazant, W, Beardsmore, D, Beck, T, Behjati, S, Behren, A, Bell, C, Beltran, S, Benz, C, Berchuck, A, Bergmann, A, Bergstrom, E, Berman, B, Berney, D, Bernhart, S, Beroukhim, R, Berrios, M, Bersani, S, Bertl, J, Betancourt, M, Bhandari, V, Bhosle, S, Biankin, A, Bigner, D, Binder, H, Birney, E, Birrer, M, Biswas, N, Bjerkehagen, B, Bodenheimer, T, Boice, L, Bonizzato, G, De Bono, J, Boot, A, Bootwalla, M, Borg, A, Borkhardt, A, Boroevich, K, Borozan, I, Borst, C, Bosenberg, M, Bosio, M, Boultwood, J, Bourque, G, Bova, G, Bowen, D, Bowlby, R, Bowtell, D, Boyault, S, Boyce, R, Boyd, J, Brazma, A, Brennan, P, Brewer, D, Brinkman, A, Bristow, R, Broaddus, R, Brock, J, Brock, M, Broeks, A, Brooks, A, Brooks, D, Brors, B, Brunak, S, Bruxner, T, Bruzos, A, Buchholz, C, Bullman, S, Burke, H, Burkhardt, B, Burns, K, Busanovich, J, Bustamante, C, Butte, A, Byrne, N, Borresen-Dale, A, Caesar-Johnson, S, Cafferkey, A, Cahill, D, Calabrese, C, Caldas, C, Calvo, F, Camacho, N, Campbell, P, Campo, E, Cantu, C, Cao, S, Carey, T, Carlevaro-Fita, J, Carlsen, R, Cataldo, I, Cazzola, M, Cebon, J, Cerfolio, R, Chadwick, D, Chakravarty, D, Chalmers, D, Chan, C, Chan, K, Chan-Seng-Yue, M, Chandan, V, Chang, D, Chanock, S, Chantrill, L, Chateigner, A, Chatterjee, N, Chayama, K, Chen, H, Chen, J, Chen, Y, Chen, Z, Cherniack, A, Chien, J, Chiew, Y, Chin, S, Cho, J, Cho, S, Choi, J, Choi, W, Chomienne, C, Choo, S, Chou, A, Christ, A, Christie, E, Chuah, E, Cibulskis, C, Cibulskis, K, Cingarlini, S, Clapham, P, Claviez, A, Cleary, S, Cloonan, N, Cmero, M, Collins, C, Connor, A, Cooke, S, Cooper, C, Cope, L, Corbo, V, Cordes, M, Cordner, S, Cortes-Ciriano, I, Cowin, P, Craft, B, Craft, D, Creighton, C, Cun, Y, Curley, E, Cutcutache, I, Czajka, K, Czerniak, B, Dagg, R, Danilova, L, Davi, M, Davidson, N, Davies, H, Davis, I, Davis-Dusenbery, B, Dawson, K, De La Vega, F, De Paoli-Iseppi, R, Defreitas, T, Dei Tos, A, Delaneau, O, Demchok, J, Demeulemeester, J, Demidov, G, Demircioglu, D, Dennis, N, Denroche, R, Dentro, S, Desai, N, Deshpande, V, Deshwar, A, Desmedt, C, Deu-Pons, J, Dhalla, N, Dhani, N, Dhingra, P, Dhir, R, Dibiase, A, Diamanti, K, Ding, S, Dinh, H, Dirix, L, Doddapaneni, H, Donmez, N, Dow, M, Drapkin, R, Drews, R, Serge, S, Dudderidge, T, Dueso-Barroso, A, Dunford, A, Dunn, M, Duthie, F, Dutton-Regester, K, Eagles, J, Easton, D, Edmonds, S, Edwards, P, Edwards, S, Eeles, R, Ehinger, A, Eils, J, El-Naggar, A, Eldridge, M, Erkek, S, Escaramis, G, Estivill, X, Etemadmoghadam, D, Eyfjord, J, Faltas, B, Fan, D, Faquin, W, Farcas, C, Fassan, M, Fatima, A, Favero, F, Fayzullaev, N, Felau, I, Fereday, S, Ferguson, M, Ferretti, V, Feuerbach, L, Field, M, Fink, J, Finocchiaro, G, Fisher, C, Fittall, M, Fitzgerald, A, Fitzgerald, R, Flanagan, A, Fleshner, N, Flicek, P, Foekens, J, Fong, K, Fonseca, N, Foster, C, Fox, N, Fraser, M, Frazer, S, Frenkel-Morgenstern, M, Friedman, W, Frigola, J, Fronick, C, Fujimoto, A, Fujita, M, Fukayama, M, Fulton, L, Furuta, M, Futreal, P, Fullgrabe, A, Gabriel, S, Gallinger, S, Gambacorti Passerini, C, Gao, J, Garraway, L, Garred, O, Garrison, E, Garsed, D, Gehlenborg, N, George, J, Gerhard, D, Gerhauser, C, Gershenwald, J, Gerstung, M, Ghori, M, Ghossein, R, Giama, N, Gibbs, R, Gill, A, Gill, P, Giri, D, Glodzik, D, Gnanapragasam, V, Goebler, M, Goldman, M, Gomez, C, Gonzalez-Perez, A, Gordenin, D, Gossage, J, Gotoh, K, Govindan, R, Grabau, D, Graham, J, Grant, R, Green, A, Green, E, Greger, L, Grehan, N, Grimaldi, S, Grimmond, S, Grossman, R, Grundhoff, A, Gundem, G, Guo, Q, Gupta, M, Gupta, S, Gut, M, Goke, J, Ha, G, Haake, A, Haan, D, Haas, S, Haase, K, Haber, J, Habermann, N, Haider, S, Hama, N, Hamdy, F, Hamilton, A, Hamilton, M, Han, L, Hanna, G, Hansmann, M, Haradhvala, N, Harismendy, O, Harliwong, I, Harmanci, A, Harrington, E, Hasegawa, T, Hawkins, S, Hayami, S, Hayashi, S, Hayes, D, Hayes, S, Hayward, N, Hazell, S, He, Y, Heath, A, Heath, S, Hedley, D, Hegde, A, Heiman, D, Heins, Z, Heisler, L, Hellstrom-Lindberg, E, Helmy, M, Heo, S, Hepperla, A, Heredia-Genestar, J, Herrmann, C, Hersey, P, Hilmarsdottir, H, Hirano, S, Hiraoka, N, Hoadley, K, Hobolth, A, Hodzic, E, Hoell, J, Hoffmann, S, Hofmann, O, Holbrook, A, Holik, A, Hollingsworth, M, Holmes, O, Holt, R, Hong, C, Hong, E, Hong, J, Hooijer, G, Hornshoj, H, Hosoda, F, Hou, Y, Hovestadt, V, Howat, W, Hoyle, A, Hruban, R, Hu, J, Hua, X, Huang, K, Huang, M, Huber, W, Hudson, T, Hummel, M, Hung, J, Huntsman, D, Hupp, T, Huse, J, Huska, M, Hubschmann, D, Iacobuzio-Donahue, C, Imbusch, C, Imielinski, M, Imoto, S, Isaacs, W, Isaev, K, Ishikawa, S, Iskar, M, Islam, S, Ittmann, M, Ivkovic, S, Izarzugaza, J, Jacquemier, J, Jakrot, V, Jamieson, N, Jang, G, Jang, S, Jayaseelan, J, Jayasinghe, R, Jefferys, S, Jegalian, K, Jennings, J, Jeon, S, Jerman, L, Ji, Y, Jiao, W, Johansson, P, Johns, A, Johns, J, Johnson, R, Johnson, T, Jolly, C, Joly, Y, Jonasson, J, Jones, C, Jones, N, Jones, S, Jonkers, J, Ju, Y, Juhl, H, Juul, M, Juul, R, Juul, S, Kabbe, R, Kahles, A, Kahraman, A, Kaiser, V, Kakavand, H, Kalimuthu, S, von Kalle, C, Kang, K, Karaszi, K, Karlan, B, Karlic, R, Karsch, D, Kassahn, K, Katai, H, Kato, M, Katoh, H, Kawakami, Y, Kay, J, Kazakoff, S, Kazanov, M, Keays, M, Kebebew, E, Kefford, R, Kellis, M, Kench, J, Kennedy, C, Kerssemakers, J, Khoo, D, Khoo, V, Khuntikeo, N, Khurana, E, Kilpinen, H, Kim, J, Kim, Y, King, T, Klapper, W, Klimczak, L, Knappskog, S, Kneba, M, Knoppers, B, Koh, Y, Jan, K, Komura, D, Komura, M, Kong, G, Kool, M, Korbel, J, Korchina, V, Korshunov, A, Koscher, M, Koster, R, Kote-Jarai, Z, Koures, A, Kovacevic, M, Kremeyer, B, Kretzmer, H, Kreuz, M, Krishnamurthy, S, Kube, D, Kumar, K, Kumar, P, Kundra, R, Kubler, K, Kuppers, R, Lagergren, J, Lai, P, Laird, P, Lakhani, S, Lalonde, E, Lamaze, F, Lambert, A, Lander, E, Landgraf, P, Landoni, L, Langerod, A, Lanzos, A, Larsimont, D, Larsson, E, Lathrop, M, Lau, L, Lawerenz, C, Lawlor, R, Lawrence, M, Lazar, A, Le, X, Lee, D, Lee, E, Lee, H, Lee, J, Lee, M, Lee-Six, H, Lehmann, K, Lehrach, H, Lenze, D, Leonard, C, Leongamornlert, D, Letourneau, L, Levine, D, Lewis, L, Ley, T, Li, C, Li, H, Li, J, Li, L, Li, X, Li, Y, Liang, H, Liang, S, Lichter, P, Lin, P, Lin, Z, Linehan, W, Lingjaerde, O, Liu, D, Liu, E, Liu, F, Liu, J, Liu, X, Livingstone, J, Livni, N, Lochovsky, L, Loeffler, M, Long, G, Lopez-Guillermo, A, Lou, S, Louis, D, Lovat, L, Lu, Y, Luchini, C, Lungu, I, Luo, X, Luxton, H, Lynch, A, Lype, L, Lopez, C, Lopez-Otin, C, Ma, Y, Macgrogan, G, Macrae, S, Macintyre, G, Madsen, T, Maejima, K, Mafficini, A, Maglinte, D, Maitra, A, Majumder, P, Malcovati, L, Malikic, S, Malleo, G, Mann, G, Mantovani-Loffler, L, Marchal, K, Marchegiani, G, Mardis, E, Margolin, A, Marin, M, Markowetz, F, Markowski, J, Marks, J, Marques-Bonet, T, Marra, M, Marsden, L, Martens, J, Martin, S, Martin-Subero, J, Martincorena, I, Martinez-Fundichely, A, Massie, C, Matthew, T, Matthews, L, Mayer, E, Mayes, S, Mayo, M, Mbabaali, F, Mccune, K, Mcdermott, U, Mcgillivray, P, Mcpherson, J, Mcpherson, T, Meier, S, Meng, A, Meng, S, Merrett, N, Merson, S, Meyerson, M, Mieczkowski, P, Mihaiescu, G, Mijalkovic, S, Mijalkovic-Lazic, A, Mikkelsen, T, Milella, M, Mileshkin, L, Miller, C, Miller, D, Miller, J, Minner, S, Miotto, M, Arnau, G, Mirabello, L, Mitchell, C, Mitchell, T, Miyano, S, Miyoshi, N, Mizuno, S, Molnar-Gabor, F, Moore, M, Moore, R, Morganella, S, Morris, Q, Morrison, C, Mose, L, Moser, C, Muinos, F, Mularoni, L, Mungall, A, Mungall, K, Musgrove, E, Mustonen, V, Mutch, D, Muyas, F, Muzny, D, Munoz, A, Myers, J, Myklebost, O, Moller, P, Nagae, G, Nagrial, A, Nahal-Bose, H, Nakagama, H, Nakagawa, H, Nakamura, H, Nakamura, T, Nakano, K, Nandi, T, Nangalia, J, Nastic, M, Navarro, A, Navarro, F, Neal, D, Nettekoven, G, Newell, F, Newhouse, S, Newton, Y, Ng, A, Nicholson, J, Nicol, D, Nie, Y, Nielsen, G, Nik-Zainal, S, Noble, M, Nones, K, Northcott, P, Notta, F, O'Connor, B, O'Donnell, P, O'Donovan, M, O'Meara, S, O'Neill, B, O'Neill, J, Ocana, D, Ochoa, A, Oesper, L, Ogden, C, Ohdan, H, Ohi, K, Ohno-Machado, L, Oien, K, Ojesina, A, Ojima, H, Okusaka, T, Omberg, L, Ong, C, Ott, G, Ouellette, B, P'Ng, C, Paczkowska, M, Paiella, S, Pairojkul, C, Pajic, M, Pan-Hammarstrom, Q, Papaemmanuil, E, Papatheodorou, I, Park, J, Park, K, Park, P, Parker, J, Parsons, S, Pass, H, Pasternack, D, Pastore, A, Patch, A, Pauporte, I, Pea, A, Pearson, J, Pedamallu, C, Pederzoli, P, Peifer, M, Pennell, N, Perou, C, Petersen, G, Petrelli, N, Petryszak, R, Pfister, S, Phillips, M, Pich, O, Pickett, H, Pihl, T, Pillay, N, Pinder, S, Pinese, M, Pinho, A, Pitkanen, E, Pivot, X, Pineiro-Yanez, E, Planko, L, Plass, C, Polak, P, Pons, T, Popescu, I, Potapova, O, Prasad, A, Preston, S, Prinz, M, Pritchard, A, Prokopec, S, Provenzano, E, Puente, X, Puig, S, Pulido-Tamayo, S, Pupo, G, Purdie, C, Quinn, M, Rabionet, R, Rader, J, Radlwimmer, B, Radovic, P, Raeder, B, Ramakrishna, M, Ramakrishnan, K, Ramalingam, S, Raphael, B, Rathmell, W, Rausch, T, Reifenberger, G, Reimand, J, Reis-Filho, J, Reuter, V, Reyes-Salazar, I, Reyna, M, Riazalhosseini, Y, Richardson, A, Richter, J, Ringel, M, Ringner, M, Rino, Y, Rippe, K, Roach, J, Roberts, L, Roberts, N, Roberts, S, Robertson, A, Rodriguez, J, Rodriguez-Martin, B, Rodriguez-Gonzalez, F, Roehrl, M, Rohde, M, Rokutan, H, Romieu, G, Rooman, I, Roques, T, Rosebrock, D, Rosenberg, M, Rosenstiel, P, Rosenwald, A, Rowe, E, Rozen, S, Rubanova, Y, Rubin, M, Rubio-Perez, C, Rudneva, V, Rusev, B, Ruzzenente, A, Ratsch, G, Sabarinathan, R, Sabelnykova, V, Sadeghi, S, Saini, N, Saito-Adachi, M, Salcedo, A, Salgado, R, Salichos, L, Sallari, R, Saller, C, Salvia, R, Sam, M, Samra, J, Sanchez-Vega, F, Sander, C, Sanders, G, Sarin, R, Sasaki-Oku, A, Sauer, T, Sauter, G, Saw, R, Scardoni, M, Scarlett, C, Scarpa, A, Scelo, G, Schadendorf, D, Schein, J, Schilhabel, M, Schlomm, T, Schmidt, H, Schramm, S, Schreiber, S, Schultz, N, Schumacher, S, Schwarz, R, Scolyer, R, Scott, D, Scully, R, Seethala, R, Segre, A, Selander, I, Semple, C, Senbabaoglu, Y, Sengupta, S, Sereni, E, Serra, S, Sgroi, D, Shackleton, M, Shah, N, Shahabi, S, Shang, C, Shang, P, Shapira, O, Shelton, T, Shen, C, Shen, H, Shepherd, R, Shi, R, Shi, Y, Shiah, Y, Shibata, T, Shih, J, Shimizu, E, Shimizu, K, Shin, S, Shiraishi, Y, Shmaya, T, Shmulevich, I, Shorser, S, Short, C, Shrestha, R, Shringarpure, S, Shriver, C, Shuai, S, Sidiropoulos, N, Siebert, R, Sieuwerts, A, Sieverling, L, Signoretti, S, Sikora, K, Simbolo, M, Simon, R, Simons, J, Simpson, P, Singer, S, Sinnott-Armstrong, N, Sipahimalani, P, Skelly, T, Smid, M, Smith, J, Smith-McCune, K, Socci, N, Soloway, M, Song, L, Sood, A, Sothi, S, Sotiriou, C, Soulette, C, Span, P, Spellman, P, Sperandio, N, Spillane, A, Spiro, O, Spring, J, Staaf, J, Stadler, P, Staib, P, Stark, S, Stefansson, O, Stegle, O, Stein, L, Stenhouse, A, Stilgenbauer, S, Stratton, M, Stretch, J, Stunnenberg, H, Su, H, Su, X, Sun, R, Sungalee, S, Susak, H, Suzuki, A, Sweep, F, Szczepanowski, M, Sultmann, H, Yugawa, T, Tam, A, Tamborero, D, Tan, B, Tan, D, Tan, P, Tanaka, H, Taniguchi, H, Tanskanen, T, Tarabichi, M, Tarnuzzer, R, Tarpey, P, Taschuk, M, Tatsuno, K, Tavare, S, Taylor, D, Taylor-Weiner, A, Teh, B, Tembe, V, Temes, J, Thai, K, Thayer, S, Thiessen, N, Thomas, G, Thomas, S, Thompson, A, Thompson, J, Thompson, R, Thorne, H, Thorne, L, Thorogood, A, Tijanic, N, Timms, L, Tirabosco, R, Tojo, M, Tommasi, S, Toon, C, Toprak, U, Tortora, G, Tost, J, Totoki, Y, Townend, D, Traficante, N, Treilleux, I, Trotta, J, Trumper, L, Tsao, M, Tsunoda, T, Tubio, J, Tucker, O, Turkington, R, Turner, D, Tutt, A, Ueno, M, Ueno, N, Umbricht, C, Umer, H, Underwood, T, Urban, L, Urushidate, T, Ushiku, T, Uuskula-Reimand, L, Valencia, A, Van Den Berg, D, Van Laere, S, Van Loo, P, Van Meir, E, Van den Eynden, G, Van der Kwast, T, Vasudev, N, Vazquez, M, Vedururu, R, Veluvolu, U, Vembu, S, Verbeke, L, Vermeulen, P, Verrill, C, Viari, A, Vicente, D, Vicentini, C, Raghavan, K, Viksna, J, Vilain, R, Villasante, I, Vincent-Salomon, A, Visakorpi, T, Voet, D, Vyas, P, Vazquez-Garcia, I, Waddell, N, Wadelius, C, Wadi, L, Wagener, R, Wang, Q, Wang, Y, Wang, Z, Waring, P, Warnatz, H, Warrell, J, Warren, A, Wedge, D, Weichenhan, D, Weinberger, P, Weisenberger, D, Welch, I, Whalley, J, Whitaker, H, Wigle, D, Wilkerson, M, Williams, A, Wilmott, J, Wilson, G, Wilson, J, Wilson, R, Winterhoff, B, Wintersinger, J, Wiznerowicz, M, Wolf, S, Wong, B, Wong, T, Wong, W, Woo, Y, Wood, S, Wouters, B, Wright, A, Wright, D, Wright, M, Wu, C, Wu, D, Wu, G, Wu, J, Wu, K, Wu, Y, Xia, T, Xiang, Q, Xiao, X, Xing, R, Xiong, H, Xu, Q, Xu, Y, Yachida, S, Yamaguchi, R, Yamamoto, M, Yamamoto, S, Yamaue, H, Yang, F, Yang, H, Yang, J, Yang, L, Yang, S, Yang, T, Yang, Y, Yao, X, Yaspo, M, Yates, L, Yau, C, Ye, C, Yoon, C, Yoon, S, Yousif, F, Yu, J, Yu, K, Yu, W, Yu, Y, Yuan, K, Yuan, Y, Yuen, D, Zaikova, O, Zamora, J, Zapatka, M, Zenklusen, J, Zenz, T, Zeps, N, Zhang, C, Zhang, F, Zhang, H, Zhang, X, Zhang, Y, Zhang, Z, Zhao, Z, Zheng, L, Zheng, X, Zhou, W, Zhou, Y, Bin, Z, Zhu, H, Zhu, J, Zhu, S, Zou, L, Zou, X, Defazio, A, van As, N, van Deurzen, C, van de Vijver, M, van't Veer, L, von Mering, C, Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Tampere University, BioMediTech, TAYS Cancer Centre, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of St Andrews. Cellular Medicine Division, University of St Andrews. Statistics, University of St Andrews. School of Medicine, University of Zurich, Gerstein, Mark B, Ding, Li, Bailey, Matthew H [0000-0003-4526-9727], Wheeler, David A [0000-0002-9056-6299], Gerstein, Mark B [0000-0002-9746-3719], Faculty of Economic and Social Sciences and Solvay Business School, Lauri Antti Aaltonen / Principal Investigator, Genome-Scale Biology (GSB) Research Program, Department of Medical and Clinical Genetics, Organismal and Evolutionary Biology Research Programme, Helsinki Institute for Information Technology, Institute of Biotechnology, Bioinformatics, Department of Computer Science, Faculty of Medicine, and HUS Helsinki and Uusimaa Hospital District
Subjects: VARIANTS, 0302 clinical medicine, 706/648/697/129/2043, Databases, Genetic, Cancer genomics, SOMATIC POINT MUTATIONS, Càncer, lcsh:Science, Exome, Exome sequencing, Cancer, Base Composition, Neoplasms -- genetics, 1184 Genetics, developmental biology, physiology, 3100 General Physics and Astronomy, 3. Good health, 030220 oncology & carcinogenesis, Science & Technology - Other Topics, Transformació genètica, Genetic databases, Erfðarannsóknir, Human, GENES, Science, 1600 General Chemistry, General Biochemistry, Genetics and Molecular Biology, RC0254, 03 medical and health sciences, Genetic, SDG 3 - Good Health and Well-being, 1300 General Biochemistry, Genetics and Molecular Biology, Exome Sequencing, Genetics, Humans, Author Correction, Retrospective Studies, Whole genome sequencing, Comparative genomics, Science & Technology, RC0254 Neoplasms. Tumors. Oncology (including Cancer), INSERTIONS, DNA, PERFORMANCE, Human genetics, Communication and replication, Cancérologie, 692/4028/67/69, Genòmica, 030104 developmental biology, Mutation, Genome mutation, Human genome, lcsh:Q, COMPREHENSIVE CHARACTERIZATION, Genètica, 0301 basic medicine, Medizin, General Physics and Astronomy, Genome, Whole Exome Sequencing, Genetic transformation, International Cancer Genome Consortium, Neoplasms, 631/114/2399, Genamengi, Medicine and Health Sciences, Medicine(all), Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Multidisciplinary, 318 Medical biotechnology, Exome -- genetics, article, Exons, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], Multidisciplinary Sciences, CAPTURE, 1181 Ecology, evolutionary biology, oncology, DNA, Intergenic, 139, Medical Genetics, Biotechnology, ICGC/TCGA Pan-Cancer Analysis, 3122 Cancers, 610 Medicine & health, 45/23, QH426 Genetics, Biology, MC3 Working Group, Databases, Germline mutation, PCAWG novel somatic mutation calling methods working group, Krabbameinsrannsóknir, Cancer Genome Atlas, Genome, Human -- genetics, ddc:610, QH426, Medicinsk genetik, Krabbamein, Intergenic, Whole Genome Sequencing, Genome, Human, Human Genome, PCAWG Consortium, DAS, General Chemistry, DELETIONS, Good Health and Well Being, 10032 Clinic for Oncology and Hematology, 3111 Biomedicine, 631/1647/2217/748
Abstract: MC3 Working Group: Rehan Akbani21, Pavana Anur22, Matthew H. Bailey1,2,3, Alex Buchanan9, Kami Chiotti9, Kyle Covington12,23, Allison Creason9, Li Ding1,2,3,20, Kyle Ellrott9, Yu Fan21, Steven Foltz1,2, Gad Getz8,14,15,16, Walker Hale12, David Haussler24,25, Julian M. Hess8,26, Carolyn M. Hutter27, Cyriac Kandoth28, Katayoon Kasaian29,30, Melpomeni Kasapi27, Dave Larson1 , Ignaty Leshchiner8, John Letaw31, Singer Ma32, Michael D. McLellan1,3,20, Yifei Men32, Gordon B. Mills33,34, Beifang Niu35, Myron Peto22, Amie Radenbaugh24, Sheila M. Reynolds36, Gordon Saksena8, Heidi Sofia27, Chip Stewart8, Adam J. Struck31, Joshua M. Stuart24,37, Wenyi Wang21, John N. Weinstein38, David A. Wheeler12,13, Christopher K. Wong24,39, Liu Xi12 & Kai Ye40,41 21Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. 22Molecular and Medical Genetics, OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA. 23Castle Biosciences Inc, Friendswood, TX 77546, USA. 24UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA 95064, USA. 25Howard Hughes Medical Institute, University of California Santa Cruz, Santa Cruz, CA 95064, USA. 26Massachusetts General Hospital Center for Cancer Research, Charlestown, MA 02114, USA. 27National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20894, USA. 28Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. 29Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada. 30Canada’s Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V5Z 4S6, Canada. 31Computational Biology Program, School of Medicine, Oregon Health and Science University, Portland, OR 97239, USA. 32DNAnexus Inc, Mountain View, CA 94040, USA. 33Department of Systems Biology, UT MD Anderson Cancer Center, Houston, TX 77030, USA. 34Precision Oncology, OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA. 35Computer Network Information Center, Chinese Academy of Sciences, Beijing, China. 36Institute for Systems Biology, Seattle, WA 98109, USA. 37Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA 95064, USA. 38Department of Bioinformatics and Computational Biology and Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. 39Biomolecular Engineering Department, University of California Santa Cruz, Santa Cruz, CA 95064, USA. 40School of Elect, PCAWG novel somatic mutation calling methods working group: Matthew H. Bailey1,2,3, Beifang Niu35, Matthias Bieg42,43, Paul C. Boutros6,44,45,46, Ivo Buchhalter43,47,48, Adam P. Butler49, Ken Chen50, Zechen Chong51, Li Ding1,2,3,20, Oliver Drechsel52,53, Lewis Jonathan Dursi6,7, Roland Eils47,48,54,55, Kyle Ellrott9, Shadrielle M. G. Espiritu6, Yu Fan21, Robert S. Fulton1,3,20, Shengjie Gao56, Josep L. l. Gelpi57,58, Mark B. Gerstein5,18,19, Gad Getz8,14,15,16, Santiago Gonzalez59,60, Ivo G. Gut52,61, Faraz Hach62,63, Michael C. Heinold47,48, Julian M. Hess8,26, Jonathan Hinton49, Taobo Hu64, Vincent Huang6, Yi Huang65,66, Barbara Hutter43,67,68, David R. Jones49, Jongsun Jung69, Natalie Jäger47, Hyung-Lae Kim70, Kortine Kleinheinz47,48, Sushant Kumar5,19, Yogesh Kumar64, Christopher M. Lalansingh6, Ignaty Leshchiner8, Ivica Letunic71, Dimitri Livitz8, Eric Z. Ma64, Yosef E. Maruvka8,26,72, R. Jay Mashl1,2, Michael D. McLellan1,3,20, Andrew Menzies49, Ana Milovanovic57, Morten Muhlig Nielsen73, Stephan Ossowski52,53,74, Nagarajan Paramasivam43,47, Jakob Skou Pedersen73,75, Marc D. Perry76,77, Montserrat Puiggròs57, Keiran M. Raine49, Esther Rheinbay8,14,72, Romina Royo57, S. Cenk Sahinalp62,78,79, Gordon Saksena8, Iman Sarrafi62,78, Matthias Schlesner47,80, Jared T. Simpson6,17, Lucy Stebbings49, Chip Stewart8, Miranda D. Stobbe52,61, Jon W. Teague49, Grace Tiao8, David Torrents57,81, Jeremiah A. Wala8,14,82, Jiayin Wang1,40,66, Wenyi Wang21, Sebastian M. Waszak60, Joachim Weischenfeldt60,83,84, Michael C. Wendl1,10,11, Johannes Werner47,85, Zhenggang Wu64, Hong Xue64, Sergei Yakneen60, Takafumi N. Yamaguchi6, Kai Ye40,41, Venkata D. Yellapantula20,86, Christina K. Yung76 & Junjun Zhang76, PCAWG Consortium: Lauri A. Aaltonen87, Federico Abascal49, Adam Abeshouse88, Hiroyuki Aburatani89, David J. Adams49, Nishant Agrawal90, Keun Soo Ahn91, Sung-Min Ahn92, Hiroshi Aikata93, Rehan Akbani21, Kadir C. Akdemir50, Hikmat Al-Ahmadie88, Sultan T. Al-Sedairy94, Fatima Al-Shahrour95, Malik Alawi96,97, Monique Albert98, Kenneth Aldape99,100, Ludmil B. Alexandrov49,101,102, Adrian Ally30, Kathryn Alsop103, Eva G. Alvarez104,105,106, Fernanda Amary107, Samirkumar B. Amin108,109,110, Brice Aminou76, Ole Ammerpohl111,112, Matthew J. Anderson113, Yeng Ang114, Davide Antonello115, Pavana Anur22, Samuel Aparicio116, Elizabeth L. Appelbaum1,117, Yasuhito Arai118, Axel Aretz119, Koji Arihiro93, Shun-ichi Ariizumi120, Joshua Armenia121, Laurent Arnould122, Sylvia Asa123,124, Yassen Assenov125, Gurnit Atwal6,126,127, Sietse Aukema112,128, J. Todd Auman129, Miriam R. Aure130, Philip Awadalla6,126, Marta Aymerich131, Gary D. Bader126, Adrian Baez-Ortega132, Matthew H. Bailey1,2,3, Peter J. Bailey133, Miruna Balasundaram30, Saianand Balu134, Pratiti Bandopadhayay8,135,136, Rosamonde E. Banks137, Stefano Barbi138, Andrew P. Barbour139,140, Jonathan Barenboim6, Jill Barnholtz-Sloan141,142, Hugh Barr143, Elisabet Barrera59, John Bartlett98,144, Javier Bartolome57, Claudio Bassi115, Oliver F. Bathe145,146, Daniel Baumhoer147, Prashant Bavi148, Stephen B. Baylin149,150, Wojciech Bazant59, Duncan Beardsmore151, Timothy A. Beck152,153, Sam Behjati49, Andreas Behren154, Beifang Niu35, Cindy Bell155, Sergi Beltran52,61, Christopher Benz156, Andrew Berchuck157, Anke K. Bergmann158, Erik N. Bergstrom101,102, Benjamin P. Berman159,160,161, Daniel M. Berney162, Stephan H. Bernhart163,164,165, Rameen Beroukhim8,14,82, Mario Berrios166, Samantha Bersani167, Johanna Bertl73,168, Miguel Betancourt169, Vinayak Bhandari6,44, Shriram G. Bhosle49, Andrew V. Biankin133,170,171,172, Matthias Bieg42,43, Darell Bigner173, Hans Binder163,164, Ewan Birney59, Michael Birrer72, Nidhan K. Biswas174, Bodil Bjerkehagen147,175, Tom Bodenheimer134, Lori Boice176, Giada Bonizzato177, Johann S. De Bono178, Arnoud Boot179,180, Moiz S. Bootwalla166, Ake Borg181, Arndt Borkhardt182, Keith A. Boroevich183,184, Ivan Borozan6, Christoph Borst185, Marcus Bosenberg186, Mattia Bosio52,53,57, Jacqueline Boultwood187, Guillaume Bourque188,189, Paul C. Boutros6,44,45,46, G. Steven Bova190, David T. Bowen49,191, Reanne Bowlby30, David D. L. Bowtell103, Sandrine Boyault192, Rich Boyce59, Jeffrey Boyd193, Alvis Brazma59, Paul Brennan194, Daniel S. Brewer195,196, Arie B. Brinkman197, Robert G. Bristow44,198,199,200,201, Russell R. Broaddus99, Jane E. Brock202, Malcolm Brock203, Annegien Broeks204, Angela N. Brooks8,24,37,82, Denise Brooks30, Benedikt Brors67,205,206, Søren Brunak207,208, Timothy J. C. Bruxner113,209, Alicia L. Bruzos104,105,106, Alex Buchanan9, Ivo Buchhalter43,47,48, Christiane Buchholz210, Susan Bullman8,82, Hazel Burke211, Birgit Burkhardt212, Kathleen H. Burns213,214, John Busanovich8,215, Carlos D. Bustamante216,217, Adam P. Butler49, Atul J. Butte218, Niall J. Byrne76, Anne-Lise Børresen-Dale130,219, Samantha J. Caesar-Johnson220, Andy Cafferkey59, Declan Cahill221, Claudia Calabrese59,60, Carlos Caldas222,223, Fabien Calvo224, Niedzica Camacho178, Peter J. Campbell49,225, Elias Campo226,227, Cinzia Cantù177, Shaolong Cao21, Thomas E. Carey228, Joana Carlevaro-Fita229,230,231, Rebecca Carlsen30, Ivana Cataldo167,177, Mario Cazzola232, Jonathan Cebon154, Robert Cerfolio233, Dianne E. Chadwick234, Dimple Chakravarty235, Don Chalmers236, Calvin Wing Yiu Chan47,237, Kin Chan238, Michelle Chan-Seng-Yue148, Vishal S. Chandan239, David K. Chang133,170, Stephen J. Chanock240, Lorraine A. Chantrill170,241, Aurélien Chateigner76,242, Nilanjan Chatterjee149,243, Kazuaki Chayama93, Hsiao-Wei Chen114,121, Jieming Chen218, Ken Chen50, Yiwen Chen21, Zhaohong Chen244, Andrew D. Cherniack8,82, Jeremy Chien245, Yoke-Eng Chiew246,247, Suet-Feung Chin222,223, Juok Cho8, Sunghoon Cho248, Jung Kyoon Choi249, Wan Choi250, Christine Chomienne251, Zechen Chong51, Su Pin Choo252, Angela Chou170,246, Angelika N. Christ113, Elizabeth L. Christie103, Eric Chuah30, Carrie Cibulskis8, Kristian Cibulskis8, Sara Cingarlini253, Peter Clapham49, Alexander Claviez254, Sean Cleary148,255, Nicole Cloonan256, Marek Cmero257,258,259, Colin C. Collins62, Ashton A. Connor255,260, Susanna L. Cooke133, Colin S. Cooper178,196,261, Leslie Cope149, Vincenzo Corbo138,177, Matthew G. Cordes1,262, Stephen M. Cordner263, Isidro Cortés-Ciriano264,265,266, Kyle Covington12,23, Prue A. Cowin267, Brian Craft24, David Craft8,268, Chad J. Creighton269, Yupeng Cun270, Erin Curley271, Ioana Cutcutache179,180, Karolina Czajka272, Bogdan Czerniak99,273, Rebecca A. Dagg274, Ludmila Danilova149, Maria Vittoria Davi275, Natalie R. Davidson276,277,278,279,280, Helen Davies49,281,282, Ian J. Davis283, Brandi N. Davis-Dusenbery284, Kevin J. Dawson49, Francisco M. De La Vega216,217,285, Ricardo De Paoli-Iseppi211, Timothy Defreitas8, Angelo P. Dei Tos286, Olivier Delaneau287,288,289, John A. Demchok220, Jonas Demeulemeester290,291, German M. Demidov52,53,74, Deniz Demircioğlu292,293, Nening M. Dennis221, Robert E. Denroche148, Stefan C. Dentro49,290,294, Nikita Desai76, Vikram Deshpande72, Amit G. Deshwar295, Christine Desmedt296,297, Jordi Deu-Pons298,299, Noreen Dhalla30, Neesha C. Dhani300, Priyanka Dhingra301,302, Rajiv Dhir303, Anthony DiBiase304, Klev Diamanti305, Li Ding1,2,3,20, Shuai Ding306, Huy Q. Dinh159, Luc Dirix307, HarshaVardhan Doddapaneni12, Nilgun Donmez62,78, Michelle T. Dow244, Ronny Drapkin308, Oliver Drechsel52,53, Ruben M. Drews223, Serge Serge49, Tim Dudderidge150,221, Ana Dueso-Barroso57, Andrew J. Dunford8, Michael Dunn309, Lewis Jonathan Dursi6,7, Fraser R. Duthie133,310, Ken Dutton-Regester311, Jenna Eagles272, Douglas F. Easton312,313, Stuart Edmonds314, Paul A. Edwards223,315, Sandra E. Edwards178, Rosalind A. Eeles178,221, Anna Ehinger316, Juergen Eils54,55, Roland Eils47,48,54,55, Adel El-Naggar99,273, Matthew Eldridge223, Kyle Ellrott9, Serap Erkek60, Georgia Escaramis53,317,318, Shadrielle M. G. Espiritu6, Xavier Estivill53,319, Dariush Etemadmoghadam103, Jorunn E. Eyfjord320, Bishoy M. Faltas280, Daiming Fan321, Yu Fan21, William C. Faquin72, Claudiu Farcas244, Matteo Fassan322, Aquila Fatima323, Francesco Favero324, Nodirjon Fayzullaev76, Ina Felau220, Sian Fereday103, Martin L. Ferguson325, Vincent Ferretti76,326, Lars Feuerbach205, Matthew A. Field327, J. Lynn Fink57,113, Gaetano Finocchiaro328, Cyril Fisher221, Matthew W. Fittall290, Anna Fitzgerald329, Rebecca C. Fitzgerald282, Adrienne M. Flanagan330, Neil E. Fleshner331, Paul Flicek59, John A. Foekens332, Kwun M. Fong333, Nuno A. Fonseca59,334, Christopher S. Foster335,336, Natalie S. Fox6, Michael Fraser6, Scott Frazer8, Milana Frenkel-Morgenstern337, William Friedman338, Joan Frigola298, Catrina C. Fronick1,262, Akihiro Fujimoto184, Masashi Fujita184, Masashi Fukayama339, Lucinda A. Fulton1 , Robert S. Fulton1,3,20, Mayuko Furuta184, P. Andrew Futreal340, Anja Füllgrabe59, Stacey B. Gabriel8, Steven Gallinger148,255,260, Carlo Gambacorti-Passerini341, Jianjiong Gao121, Shengjie Gao56, Levi Garraway82, Øystein Garred342, Erik Garrison49, Dale W. Garsed103, Nils Gehlenborg8,343, Josep L. l. Gelpi57,58, Joshy George110, Daniela S. Gerhard344, Clarissa Gerhauser345, Jeffrey E. Gershenwald346,347, Mark B. Gerstein5,18,19, Moritz Gerstung59,60, Gad Getz8,14,15,16, Mohammed Ghori49, Ronald Ghossein348, Nasra H. Giama349, Richard A. Gibbs12, Anthony J. Gill170,350, Pelvender Gill351, Dilip D. Giri348, Dominik Glodzik49, Vincent J. Gnanapragasam352,353, Maria Elisabeth Goebler354, Mary J. Goldman24, Carmen Gomez355, Santiago Gonzalez59,60, Abel Gonzalez-Perez298,299,356, Dmitry A. Gordenin357, James Gossage358, Kunihito Gotoh359, Ramaswamy Govindan3, Dorthe Grabau360, Janet S. Graham133,361, Robert C. Grant148,260, Anthony R. Green315, Eric Green27, Liliana Greger59, Nicola Grehan282, Sonia Grimaldi177, Sean M. Grimmond362, Robert L. Grossman363, Adam Grundhoff97,364, Gunes Gundem88, Qianyun Guo75, Manaswi Gupta8, Shailja Gupta365, Ivo G. Gut52,61, Marta Gut52,61, Jonathan Göke292,366, Gavin Ha8, Andrea Haake111, David Haan37, Siegfried Haas185, Kerstin Haase290, James E. Haber367, Nina Habermann60, Faraz Hach62,63, Syed Haider6, Natsuko Hama118, Freddie C. Hamdy351, Anne Hamilton267, Mark P. Hamilton368, Leng Han369, George B. Hanna370, Martin Hansmann371, Nicholas J. Haradhvala8,72, Olivier Harismendy102,372, Ivon Harliwong113, Arif O. Harmanci5,373, Eoghan Harrington374, Takanori Hasegawa375, David Haussler24,25, Steve Hawkins223, Shinya Hayami376, Shuto Hayashi375, D. Neil Hayes134,377,378, Stephen J. Hayes379,380, Nicholas K. Hayward211,311, Steven Hazell221, Yao He381, Allison P. Heath382, Simon C. Heath52,61, David Hedley300, Apurva M. Hegde38, David I. Heiman8, Michael C. Heinold47,48, Zachary Heins88, Lawrence E. Heisler152, Eva Hellstrom-Lindberg383, Mohamed Helmy384, Seong Gu Heo385, Austin J. Hepperla134, José María Heredia-Genestar386, Carl Herrmann47,48,387, Peter Hersey211, Julian M. Hess8,26, Holmfridur Hilmarsdottir320, Jonathan Hinton49, Satoshi Hirano388, Nobuyoshi Hiraoka389, Katherine A. Hoadley134,390, Asger Hobolth75,168, Ermin Hodzic78, Jessica I. Hoell182, Steve Hoffmann163,164,165,391, Oliver Hofmann392, Andrea Holbrook166, Aliaksei Z. Holik53, Michael A. Hollingsworth393, Oliver Holmes209,311, Robert A. Holt30, Chen Hong205,237, Eun Pyo Hong385, Jongwhi H. Hong394, Gerrit K. Hooijer395, Henrik Hornshøj73, Fumie Hosoda118, Yong Hou56,396, Volker Hovestadt397, William Howat352, Alan P. Hoyle134, Ralph H. Hruban149, Jianhong Hu12, Taobo Hu64, Xing Hua240, Kuan-lin Huang1,398, Mei Huang176, Mi Ni Huang179,180, Vincent Huang6, Yi Huang65,66, Wolfgang Huber60, Thomas J. Hudson272,399, Michael Hummel400, Jillian A. Hung246,247, David Huntsman401, Ted R. Hupp402, Jason Huse88, Matthew R. Huska403, Barbara Hutter43,67,68, Carolyn M. Hutter27, Daniel Hübschmann48,54,404,405,406, Christine A. Iacobuzio-Donahue348, Charles David Imbusch205, Marcin Imielinski407,408, Seiya Imoto375, William B. Isaacs409, Keren Isaev6,44, Shumpei Ishikawa410, Murat Iskar397, S. M. Ashiqul Islam244, Michael Ittmann411,412,413, Sinisa Ivkovic284, Jose M. G. Izarzugaza414, Jocelyne Jacquemier415, Valerie Jakrot211, Nigel B. Jamieson133,172,416, Gun Ho Jang148, Se Jin Jang417, Joy C. Jayaseelan12, Reyka Jayasinghe1 , Stuart R. Jefferys134, Karine Jegalian418, Jennifer L. Jennings419, Seung-Hyup Jeon250, Lara Jerman60,420, Yuan Ji421,422, Wei Jiao6, Peter A. Johansson311, Amber L. Johns170, Jeremy Johns272, Rory Johnson230,423, Todd A. Johnson183, Clemency Jolly290, Yann Joly424, Jon G. Jonasson320, Corbin D. Jones425, David R. Jones49, David T. W. Jones426,427, Nic Jones428, Steven J. M. Jones30, Jos Jonkers204, Young Seok Ju49,249, Hartmut Juhl429, Jongsun Jung69, Malene Juul73, Randi Istrup Juul73, Sissel Juul374, Natalie Jäger47, Rolf Kabbe47, Andre Kahles276,277,278,279,430, Abdullah Kahraman431,432,433, Vera B. Kaiser434, Hojabr Kakavand211, Sangeetha Kalimuthu148, Christof von Kalle405, Koo Jeong Kang91, Katalin Karaszi351, Beth Karlan435, Rosa Karlić436, Dennis Karsch437, Katayoon Kasaian29,30, Karin S. Kassahn113,438, Hitoshi Katai439, Mamoru Kato440, Hiroto Katoh410, Yoshiiku Kawakami93, Jonathan D. Kay117, Stephen H. Kazakoff209,311, Marat D. Kazanov441,442,443, Maria Keays59, Electron Kebebew444,445, Richard F. Kefford446, Manolis Kellis8,447, James G. Kench170,350,448, Catherine J. Kennedy246,247, Jules N. A. Kerssemakers47, David Khoo273, Vincent Khoo221, Narong Khuntikeo115,449, Ekta Khurana301,302,450,451, Helena Kilpinen117, Hark Kyun Kim452, Hyung-Lae Kim70, Hyung-Yong Kim415, Hyunghwan Kim250, Jaegil Kim8, Jihoon Kim453, Jong K. Kim454, Youngwook Kim455,456, Tari A. King457,458,459, Wolfram Klapper128, Kortine Kleinheinz47,48, Leszek J. Klimczak460, Stian Knappskog49,461, Michael Kneba437, Bartha M. Knoppers424, Youngil Koh462,463, Jan Komorowski305,464, Daisuke Komura410, Mitsuhiro Komura375, Gu Kong415, Marcel Kool426,465, Jan O. Korbel59,60, Viktoriya Korchina12, Andrey Korshunov465, Michael Koscher465, Roelof Koster466, Zsofia Kote-Jarai178, Antonios Koures244, Milena Kovacevic284, Barbara Kremeyer49, Helene Kretzmer164,165, Markus Kreuz467, Savitri Krishnamurthy99,468, Dieter Kube469, Kiran Kumar8, Pardeep Kumar221, Sushant Kumar5,19, Yogesh Kumar64, Ritika Kundra114,121, Kirsten Kübler8,14,72, Ralf Küppers470, Jesper Lagergren383,471, Phillip H. Lai166, Peter W. Laird472, Sunil R. Lakhani473, Christopher M. Lalansingh6, Emilie Lalonde6, Fabien C. Lamaze6, Adam Lambert351, Eric Lander8, Pablo Landgraf474,475, Luca Landoni115, Anita Langerød130, Andrés Lanzós230,231,423, Denis Larsimont476, Erik Larsson477, Mark Lathrop189, Loretta M. S. Lau478, Chris Lawerenz55, Rita T. Lawlor177, Michael S. Lawrence8,72,183, Alexander J. Lazar99,108, Xuan Le479, Darlene Lee30, Donghoon Lee5, Eunjung Alice Lee480, Hee Jin Lee417, Jake June-Koo Lee264,266, Jeong-Yeon Lee481, Juhee Lee482, Ming Ta Michael Lee340, Henry Lee-Six49, Kjong-Van Lehmann276,277,278,279,430, Hans Lehrach483, Dido Lenze400, Conrad R. Leonard209,311, Daniel A. Leongamornlert49,178, Ignaty Leshchiner8, Louis Letourneau484, Ivica Letunic71, Douglas A. Levine88,485, Lora Lewis12, Tim Ley486, Chang Li56,396, Constance H. Li6,44, Haiyan Irene Li30, Jun Li21, Lin Li56, Shantao Li5, Siliang Li56,396, Xiaobo Li56,396, Xiaotong Li5, Xinyue Li56, Yilong Li49, Han Liang21, Sheng-Ben Liang234, Peter Lichter68,397, Pei Lin8, Ziao Lin8,487, W. M. Linehan488, Ole Christian Lingjærde489, Dongbing Liu56,396, Eric Minwei Liu88,301,302, Fei-Fei Liu201,490, Fenglin Liu381,491, Jia Liu492, Xingmin Liu56,396, Julie Livingstone6, Dimitri Livitz8, Naomi Livni221, Lucas Lochovsky5,19,110, Markus Loeffler467, Georgina V. Long211, Armando Lopez-Guillermo493, Shaoke Lou5,19, David N. Louis72, Laurence B. Lovat117, Yiling Lu38, Yong-Jie Lu162,494, Youyong Lu495,496,497, Claudio Luchini167, Ilinca Lungu144,148, Xuemei Luo152, Hayley J. Luxton117, Andy G. Lynch223,315,498, Lisa Lype36, Cristina López111,112, Carlos López-Otín499, Eric Z. Ma64, Yussanne Ma30, Gaetan MacGrogan500, Shona MacRae501, Geoff Macintyre223, Tobias Madsen73, Kazuhiro Maejima184, Andrea Mafficini177, Dennis T. Maglinte166,502, Arindam Maitra174, Partha P. Majumder174, Luca Malcovati232, Salem Malikic62,78, Giuseppe Malleo115, Graham J. Mann211,246,503, Luisa Mantovani-Löffler504, Kathleen Marchal505,506, Giovanni Marchegiani115, Elaine R. Mardis1,193,507, Adam A. Margolin31, Maximillian G. Marin37, Florian Markowetz223,315, Julia Markowski403, Jeffrey Marks508, Tomas Marques-Bonet61,81,386,509, Marco A. Marra30, Luke Marsden351, John W. M. Martens332, Sancha Martin49,510, Jose I. Martin-Subero81,511, Iñigo Martincorena49, Alexander Martinez-Fundichely301,302,451 Yosef E. Maruvka8,26,72, R. Jay Mashl1,2, Charlie E. Massie223, Thomas J. Matthew37, Lucy Matthews178, Erik Mayer221,512, Simon Mayes513, Michael Mayo30, Faridah Mbabaali272, Karen McCune514, Ultan McDermott49, Patrick D. McGillivray19, Michael D. McLellan1,3,20, John D. McPherson148,272,515, John R. McPherson179,180, Treasa A. McPherson260, Samuel R. Meier8, Alice Meng516, Shaowu Meng134, Andrew Menzies49, Neil D. Merrett115,517, Sue Merson178, Matthew Meyerson8,14,82, William U. Meyerson4,5, Piotr A. Mieczkowski518, George L. Mihaiescu76, Sanja Mijalkovic284, Ana Mijalkovic Mijalkovic-Lazic284, Tom Mikkelsen519, Michele Milella253, Linda Mileshkin103, Christopher A. Miller1 , David K. Miller113,170, Jessica K. Miller272, Gordon B. Mills33,34, Ana Milovanovic57, Sarah Minner520, Marco Miotto115, Gisela Mir Arnau267, Lisa Mirabello240, Chris Mitchell103, Thomas J. Mitchell49,315,352, Satoru Miyano375, Naoki Miyoshi375, Shinichi Mizuno521, Fruzsina Molnár-Gábor522, Malcolm J. Moore300, Richard A. Moore30, Sandro Morganella49, Quaid D. Morris127,490, Carl Morrison523,524, Lisle E. Mose134, Catherine D. Moser349, Ferran Muiños298,299, Loris Mularoni298,299, Andrew J. Mungall30, Karen Mungall30, Elizabeth A. Musgrove133, Ville Mustonen525,526,527, David Mutch528, Francesc Muyas52,53,74, Donna M. Muzny12, Alfonso Muñoz59, Jerome Myers529, Ola Myklebost461, Peter Möller530, Genta Nagae89, Adnan M. Nagrial170, Hardeep K. Nahal-Bose76, Hitoshi Nakagama531, Hidewaki Nakagawa184, Hiromi Nakamura118, Toru Nakamura388, Kaoru Nakano184, Tannistha Nandi532, Jyoti Nangalia49, Mia Nastic284, Arcadi Navarro61,81,386, Fabio C. P. Navarro19, David E. Neal223,352, Gerd Nettekoven533, Felicity Newell209,311, Steven J. Newhouse59, Yulia Newton37, Alvin Wei Tian Ng534, Anthony Ng535, Jonathan Nicholson49, David Nicol221, Yongzhan Nie321,536, G. Petur Nielsen72, Morten Muhlig Nielsen73, Serena Nik-Zainal49,281,282,537, Michael S. Noble8, Katia Nones209,311, Paul A. Northcott538, Faiyaz Notta148,539, Brian D. O’Connor76,540, Peter O’Donnell541, Maria O’Donovan282, Sarah O’Meara49, Brian Patrick O’Neill542, J. Robert O’Neill543, David Ocana59, Angelica Ochoa88, Layla Oesper544, Christopher Ogden221, Hideki Ohdan93, Kazuhiro Ohi375, Lucila Ohno-Machado244, Karin A. Oien523,545, Akinyemi I. Ojesina546,547,548, Hidenori Ojima549, Takuji Okusaka550, Larsson Omberg551, Choon Kiat Ong552, Stephan Ossowski52,53,74, German Ott553, B. F. Francis Ouellette76,554, Christine P’ng6, Marta Paczkowska6, Salvatore Paiella115, Chawalit Pairojkul523, Marina Pajic170, Qiang Pan-Hammarström56,555, Elli Papaemmanuil49, Irene Papatheodorou59, Nagarajan Paramasivam43,47, Ji Wan Park385, Joong-Won Park556, Keunchil Park557,558, Kiejung Park559, Peter J. Park264,266, Joel S. Parker518, Simon L. Parsons124, Harvey Pass560, Danielle Pasternack272, Alessandro Pastore276, Ann-Marie Patch209,311, Iris Pauporté251, Antonio Pea115, John V. Pearson209,311, Chandra Sekhar Pedamallu8,14,82, Jakob Skou Pedersen73,75, Paolo Pederzoli115, Martin Peifer270, Nathan A. Pennell561, Charles M. Perou129,518, Marc D. Perry76,77, Gloria M. Petersen562, Myron Peto22, Nicholas Petrelli563, Robert Petryszak59, Stefan M. Pfister426,465,564, Mark Phillips424, Oriol Pich298,299, Hilda A. Pickett478, Todd D. Pihl565, Nischalan Pillay566, Sarah Pinder567, Mark Pinese170, Andreia V. Pinho568, Esa Pitkänen60, Xavier Pivot569, Elena Piñeiro-Yáñez95, Laura Planko533, Christoph Plass345, Paz Polak8,14,15, Tirso Pons570, Irinel Popescu571, Olga Potapova572, Aparna Prasad52, Shaun R. Preston573, Manuel Prinz47, Antonia L. Pritchard311, Stephenie D. Prokopec6, Elena Provenzano574, Xose S. Puente499, Sonia Puig176, Montserrat Puiggròs57, Sergio Pulido-Tamayo505,506, Gulietta M. Pupo246, Colin A. Purdie575, Michael C. Quinn209,311, Raquel Rabionet52,53,576, Janet S. Rader577, Bernhard Radlwimmer397, Petar Radovic284, Benjamin Raeder60, Keiran M. Raine49, Manasa Ramakrishna49, Kamna Ramakrishnan49, Suresh Ramalingam578, Benjamin J. Raphael579, W. Kimryn Rathmell580, Tobias Rausch60, Guido Reifenberger475, Jüri Reimand6,44, Jorge Reis-Filho348, Victor Reuter348, Iker Reyes-Salazar298, Matthew A. Reyna579, Sheila M. Reynolds36, Esther Rheinbay8,14,72, Yasser Riazalhosseini189, Andrea L. Richardson323, Julia Richter111,128, Matthew Ringel581, Markus Ringnér181, Yasushi Rino582, Karsten Rippe405, Jeffrey Roach583, Lewis R. Roberts349, Nicola D. Roberts49, Steven A. Roberts584, A. Gordon Robertson30, Alan J. Robertson113, Javier Bartolomé Rodriguez57, Bernardo Rodriguez-Martin104,105,106, F. Germán Rodríguez-González83,332, Michael H. A. Roehrl44,123,148,234,585,586, Marius Rohde587, Hirofumi Rokutan440, Gilles Romieu588, Ilse Rooman170, Tom Roques262, Daniel Rosebrock8, Mara Rosenberg8,72, Philip C. Rosenstiel589, Andreas Rosenwald590, Edward W. Rowe221,591, Romina Royo57, Steven G. Rozen179,180,592, Yulia Rubanova17,127, Mark A. Rubin423,593,594,595,596, Carlota Rubio-Perez298,299,597, Vasilisa A. Rudneva60, Borislav C. Rusev177, Andrea Ruzzenente598, Gunnar Rätsch276,277,278,279,280,430, Radhakrishnan Sabarinathan298,299,599, Veronica Y. Sabelnykova6, Sara Sadeghi30, S. Cenk Sahinalp62,78,79, Natalie Saini357, Mihoko Saito-Adachi440, Gordon Saksena8, Adriana Salcedo6, Roberto Salgado600, Leonidas Salichos5,19, Richard Sallari8, Charles Saller601, Roberto Salvia115, Michelle Sam272, Jaswinder S. Samra115,602, Francisco Sanchez-Vega114,121, Chris Sander276,603,604, Grant Sanders134, Rajiv Sarin605, Iman Sarrafi62,78, Aya Sasaki-Oku184, Torill Sauer489, Guido Sauter520, Robyn P. M. Saw211, Maria Scardoni167, Christopher J. Scarlett170,606, Aldo Scarpa177, Ghislaine Scelo194, Dirk Schadendorf68,607, Jacqueline E. Schein30, Markus B. Schilhabel589, Matthias Schlesner47,80, Thorsten Schlomm84,608, Heather K. Schmidt1 , Sarah-Jane Schramm246, Stefan Schreiber609, Nikolaus Schultz121, Steven E. Schumacher8,323, Roland F. Schwarz59,403,405,610, Richard A. Scolyer211,448,602, David Scott428, Ralph Scully611, Raja Seethala612, Ayellet V. Segre8,613, Iris Selander260, Colin A. Semple434, Yasin Senbabaoglu276, Subhajit Sengupta614, Elisabetta Sereni115, Stefano Serra585, Dennis C. Sgroi72, Mark Shackleton103, Nimish C. Shah352, Sagedeh Shahabi234, Catherine A. Shang329, Ping Shang211, Ofer Shapira8,323, Troy Shelton271, Ciyue Shen603,604, Hui Shen615, Rebecca Shepherd49, Ruian Shi490, Yan Shi134, Yu-Jia Shiah6, Tatsuhiro Shibata118,616, Juliann Shih8,82, Eigo Shimizu375, Kiyo Shimizu617, Seung Jun Shin618, Yuichi Shiraishi375, Tal Shmaya285, Ilya Shmulevich36, Solomon I. Shorser6, Charles Short59, Raunak Shrestha62, Suyash S. Shringarpure217, Craig Shriver619, Shimin Shuai6,126, Nikos Sidiropoulos83, Reiner Siebert112,620, Anieta M. Sieuwerts332, Lina Sieverling205,237, Sabina Signoretti202,621, Katarzyna O. Sikora177, Michele Simbolo138, Ronald Simon520, Janae V. Simons134, Jared T. Simpson6,17, Peter T. Simpson473, Samuel Singer115,458, Nasa Sinnott-Armstrong8,217, Payal Sipahimalani30, Tara J. Skelly390, Marcel Smid332, Jaclyn Smith622, Karen Smith-McCune514, Nicholas D. Socci276, Heidi J. Sofia27, Matthew G. Soloway134, Lei Song240, Anil K. Sood623,624,625, Sharmila Sothi626, Christos Sotiriou244, Cameron M. Soulette37, Paul N. Span627, Paul T. Spellman22, Nicola Sperandio177, Andrew J. Spillane211, Oliver Spiro8, Jonathan Spring628, Johan Staaf181, Peter F. Stadler163,164,165, Peter Staib629, Stefan G. Stark277,279,618,630, Lucy Stebbings49, Ólafur Andri Stefánsson631, Oliver Stegle59,60,632, Lincoln D. Stein6,126, Alasdair Stenhouse633, Chip Stewart8, Stephan Stilgenbauer634, Miranda D. Stobbe52,61, Michael R. Stratton49, Jonathan R. Stretch211, Adam J. Struck31, Joshua M. Stuart24,37, Henk G. Stunnenberg396,635, Hong Su56,396, Xiaoping Su99, Ren X. Sun6, Stephanie Sungalee60, Hana Susak52,53, Akihiro Suzuki89,636, Fred Sweep637, Monika Szczepanowski128, Holger Sültmann67,638, Takashi Yugawa617, Angela Tam30, David Tamborero298,299, Benita Kiat Tee Tan639, Donghui Tan518, Patrick Tan180,532,592,640, Hiroko Tanaka375, Hirokazu Taniguchi616, Tomas J. Tanskanen641, Maxime Tarabichi49,290, Roy Tarnuzzer220, Patrick Tarpey642, Morgan L. Taschuk152, Kenji Tatsuno89, Simon Tavaré223,643, Darrin F. Taylor113, Amaro Taylor-Weiner8, Jon W. Teague49, Bin Tean Teh180,592,640,644,645, Varsha Tembe246, Javier Temes104,105, Kevin Thai76, Sarah P. Thayer393, Nina Thiessen30, Gilles Thomas646, Sarah Thomas221, Alan Thompson221, Alastair M. Thompson633, John F. Thompson211, R. Houston Thompson647, Heather Thorne103, Leigh B. Thorne176, Adrian Thorogood424, Grace Tiao8, Nebojsa Tijanic284, Lee E. Timms272, Roberto Tirabosco648, Marta Tojo106, Stefania Tommasi649, Christopher W. Toon170, Umut H. Toprak48,650, David Torrents57,81, Giampaolo Tortora651,652, Jörg Tost653, Yasushi Totoki118, David Townend654, Nadia Traficante103, Isabelle Treilleux655,656, Jean-Rémi Trotta61, Lorenz H. P. Trümper469, Ming Tsao124,539, Tatsuhiko Tsunoda183,657,658,659, Jose M. C. Tubio104,105,106, Olga Tucker660, Richard Turkington661, Daniel J. Turner513, Andrew Tutt323, Masaki Ueno376, Naoto T. Ueno662, Christopher Umbricht151,213,663, Husen M. Umer305,664, Timothy J. Underwood665, Lara Urban59,60, Tomoko Urushidate616, Tetsuo Ushiku339, Liis Uusküla-Reimand666,667, Alfonso Valencia57,81, David J. Van Den Berg166, Steven Van Laere307, Peter Van Loo290,291, Erwin G. Van Meir668, Gert G. Van den Eynden307, Theodorus Van der Kwast123, Naveen Vasudev137, Miguel Vazquez57,669, Ravikiran Vedururu267, Umadevi Veluvolu518, Shankar Vembu490,670, Lieven P. C. Verbeke506,671, Peter Vermeulen307, Clare Verrill351,672, Alain Viari177, David Vicente57, Caterina Vicentini177, K. Vijay Raghavan365, Juris Viksna673, Ricardo E. Vilain674, Izar Villasante57, Anne Vincent-Salomon635, Tapio Visakorpi190, Douglas Voet8, Paresh Vyas311,351, Ignacio Vázquez-García49,86,675,676, Nick M. Waddell209, Nicola Waddell209,311, Claes Wadelius677, Lina Wadi6, Rabea Wagener111,112, Jeremiah A. Wala8,14,82, Jian Wang56, Jiayin Wang1,40,66, Linghua Wang12, Qi Wang465, Wenyi Wang21, Yumeng Wang21, Zhining Wang220, Paul M. Waring523, Hans-Jörg Warnatz483, Jonathan Warrell5,19, Anne Y. Warren352,678, Sebastian M. Waszak60, David C. Wedge49,294,679, Dieter Weichenhan345, Paul Weinberger680, John N. Weinstein38, Joachim Weischenfeldt60,83,84, Daniel J. Weisenberger166, Ian Welch681, Michael C. Wendl1,10,11, Johannes Werner47,85, Justin P. Whalley61,682, David A. Wheeler12,13, Hayley C. Whitaker117, Dennis Wigle683, Matthew D. Wilkerson518, Ashley Williams244, James S. Wilmott211, Gavin W. Wilson6,148, Julie M. Wilson148, Richard K. Wilson1,684, Boris Winterhoff685, Jeffrey A. Wintersinger17,127,384, Maciej Wiznerowicz686,687, Stephan Wolf688, Bernice H. Wong689, Tina Wong1,30, Winghing Wong690, Youngchoon Woo250, Scott Wood209,311, Bradly G. Wouters44, Adam J. Wright6, Derek W. Wright133,691, Mark H. Wright217, Chin-Lee Wu72, Dai-Ying Wu285, Guanming Wu692, Jianmin Wu170, Kui Wu56,396, Yang Wu179,180, Zhenggang Wu64, Liu Xi12, Tian Xia693, Qian Xiang76, Xiao Xiao66, Rui Xing497, Heng Xiong56,396, Qinying Xu209,311, Yanxun Xu694, Hong Xue64, Shinichi Yachida118,695, Sergei Yakneen60, Rui Yamaguchi375, Takafumi N. Yamaguchi6, Masakazu Yamamoto120, Shogo Yamamoto89, Hiroki Yamaue376, Fan Yang490, Huanming Yang56, Jean Y. Yang696, Liming Yang220, Lixing Yang697, Shanlin Yang306, Tsun-Po Yang270, Yang Yang369, Xiaotong Yao408,698, Marie-Laure Yaspo483, Lucy Yates49, Christina Yau156, Chen Ye56,396, Kai Ye40,41, Venkata D. Yellapantula20,86, Christopher J. Yoon249, Sung-Soo Yoon463, Fouad Yousif6, Jun Yu699, Kaixian Yu700, Willie Yu701, Yingyan Yu702, Ke Yuan223,510,703, Yuan Yuan21, Denis Yuen6, Takashi Yugawa617, Christina K. Yung76, Olga Zaikova704, Jorge Zamora49,104,105,106, Marc Zapatka397, Jean C. Zenklusen220, Thorsten Zenz67, Nikolajs Zeps705,706, Cheng-Zhong Zhang8,707, Fan Zhang381, Hailei Zhang8, Hongwei Zhang494, Hongxin Zhang121, Jiashan Zhang220, Jing Zhang5, Junjun Zhang76, Xiuqing Zhang56, Xuanping Zhang66,369, Yan Zhang5,708,709, Zemin Zhang381,710, Zhongming Zhao711, Liangtao Zheng381, Xiuqing Zheng381, Wanding Zhou615, Yong Zhou56, Bin Zhu240, Hongtu Zhu700,712, Jingchun Zhu24, Shida Zhu56,396, Lihua Zou713, Xueqing Zou49, Anna deFazio246,247,714, Nicholas van As221, Carolien H. M. van Deurzen715, Marc J. van de Vijver523, L. van’t Veer716 & Christian von Mering433,717, The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.
Published: 2020

5. Systems genetics analysis identify calcium signalling defects as novel cause of congenital heart disease

Author: Canan Doganli, Gregor Dombrowsky, Alejandro Sifrim, J. David Brook, Marc-Phillip Hitz, Sabrina Gade Ellesøe, Natasja Spring Ehlers, Marlene Danner Dalgaard, Lars Allan Larsen, Marc Gewillig, Anna Wilsdon, Enrique Audain, Jeroen Breckpot, Søren Brunak, Bernard Thienpont, and Jose M. G. Izarzugaza
Subjects: Genetics, 0303 health sciences, Mutation, biology, Mechanism (biology), Disease, 030204 cardiovascular system & hematology, medicine.disease_cause, biology.organism_classification, Genetic architecture, 03 medical and health sciences, 0302 clinical medicine, medicine, Allele, Gene, Zebrafish, Exome sequencing, 030304 developmental biology
Abstract: BackgroundCongenital heart disease (CHD) occurs in almost 1% of newborn children and is considered a multifactorial disorder. CHD may segregate in families due to significant contribution of genetic factors in the disease aetiology. The aim of the study was to identify pathophysiological mechanisms in families segregating CHD.MethodsWe used whole exome sequencing to identify rare genetic variants in ninety consenting participants from 32 Danish families with recurrent CHD. We applied a systems biology approach to identify developmental mechanisms influenced by accumulation of rare variants. We used an independent cohort of 714 CHD cases and 4922 controls for replication and performed functional investigations using zebrafish as in vivo model.ResultsWe identified 1,785 genes, in which rare alleles were shared between affected individuals within a family. These genes were enriched for known cardiac developmental genes and 218 of the genes were mutated in more than one family. Our analysis revealed a functional cluster, enriched for proteins with a known participation in calcium signalling. Replication confirmed increased mutation burden of calcium-signalling genes in CHD patients. Functional investigation of zebrafish orthologues of ITPR1, PLCB2 and ADCY2 verified a role in cardiac development and suggests a combinatorial effect of inactivation of these genes.ConclusionsThe study identifies abnormal calcium signalling as a novel pathophysiological mechanism in human CHD and confirms the complex genetic architecture underlying CHD.
Published: 2019
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6. Correction: Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease

Author: Koenraad Devriendt, Gregor Andelfinger, Dianna M. Milewicz, Hans-Heiner Kramer, Alex V. Postma, Anna Wilsdon, Bernard Thienpont, Candice K. Silversides, Jose M. G. Izarzugaza, Felix Berger, Hashim Abdul-Khaliq, Philipp Hofmann, Almuth Caliebe, Aoy Tomita-Mitchell, Anne S. Bassett, Ulrike M M Bauer, Tomas W Fitzgerald, Karl Hackmann, Jeroen Breckpot, Piers E.F. Daubeney, Vidu Garg, Gregor Dombrowsky, Alexandre F.R. Stewart, Sven Dittrich, Ingo Daehnert, Enrique Audain, Mads Bak, Marc-Phillip Hitz, Karl Stamm, Anne-Karin Kahlert, Joseph S. Coselli, Yasset Perez-Riverol, Scott A. LeMaire, Lars Allan Larsen, Alejandro Sifrim, Christian R. Marshall, Matthew E. Hurles, J. David Brook, Brigitte Stiller, Bernard Keavney, Thomas Pickardt, Siddharth K. Prakash, Florian Wünnemann, Reiner Siebert, Inga Vater, Woodrow D. Benson, Michael E. Mitchell, Jill A. Rosenfeld, Kirstin Hoff, Sabine Klaassen, Human Genetics, Medical Biology, ACS - Heart failure & arrhythmias, ACS - Pulmonary hypertension & thrombosis, ACS - Amsterdam Cardiovascular Sciences, and ARD - Amsterdam Reproduction and Development
Subjects: 0301 basic medicine, Proband, Proteomics, Heart morphogenesis, Cancer Research, Heredity, Heart disease, Gene Expression, Haploinsufficiency, QH426-470, Cardiovascular Medicine, Biochemistry, Ion Channels, 0302 clinical medicine, Medical Conditions, Databases, Genetic, Medicine and Health Sciences, Morphogenesis, Copy-number variation, Genetics (clinical), Genetics, Heart development, Heart, Genomics, Congenital Heart Defects, Cardiovascular Diseases, Physical Sciences, Protein Interaction Networks, Anatomy, Network Analysis, Research Article, Heart Defects, Congenital, Computer and Information Sciences, DNA Copy Number Variations, Permutation, Cardiology, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, medicine, Congenital Disorders, Humans, Genetic Predisposition to Disease, ddc:610, Birth Defects, Gene, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Discrete Mathematics, Gene Expression Profiling, Correction, Membrane Proteins, Biology and Life Sciences, medicine.disease, 030104 developmental biology, Cardiovascular and Metabolic Diseases, Genetic Loci, Combinatorics, Cardiovascular Anatomy, Transcriptome, 030217 neurology & neurosurgery, Mathematics, Developmental Biology
Abstract: Numerous genetic studies have established a role for rare genomic variants in Congenital Heart Disease (CHD) at the copy number variation (CNV) and de novo variant (DNV) level. To identify novel haploinsufficient CHD disease genes, we performed an integrative analysis of CNVs and DNVs identified in probands with CHD including cases with sporadic thoracic aortic aneurysm. We assembled CNV data from 7,958 cases and 14,082 controls and performed a gene-wise analysis of the burden of rare genomic deletions in cases versus controls. In addition, we performed variation rate testing for DNVs identified in 2,489 parent-offspring trios. Our analysis revealed 21 genes which were significantly affected by rare CNVs and/or DNVs in probands. Fourteen of these genes have previously been associated with CHD while the remaining genes (FEZ1, MYO16, ARID1B, NALCN, WAC, KDM5B and WHSC1) have only been associated in small cases series or show new associations with CHD. In addition, a systems level analysis revealed affected protein-protein interaction networks involved in Notch signaling pathway, heart morphogenesis, DNA repair and cilia/centrosome function. Taken together, this approach highlights the importance of re-analyzing existing datasets to strengthen disease association and identify novel disease genes and pathways., Author summary Congenital heart disease (CHD) is the most common congenital anomaly and represents a major global health burden. Multiple studies have identified a key genetic component contributing to the aetiology of CHD. However, despite the advances in the field of CHD within the last three decades, the genetic causes underlying CHD are still not fully understood. Herein we have assembled a large patient CHD cohort and performed a data-driven meta-analysis of genomic variants in CHD. This analysis has allowed us to strengthen the disease association of known CHD genes, as well as identifying novel haploinsufficient CHD candidate genes.
Published: 2021

7. Pathway and network analysis of more than 2,500 whole cancer genomes

Author: Matthew A. Reyna, Miguel Vazquez, Icgc, Kathleen Marchal, C. von Mering, Priyanka Dhingra, Søren Brunak, Marta Paczkowska, Jakob Skou Pedersen, D. Haan, Pcawg Drivers, Benjamin J. Raphael, Jose M. G. Izarzugaza, Jueri Reimand, Sahinalp Sc, S. Pulido Tamayo, Lina Wadi, Jonathan Barenboim, Ekta Khurana, Gad Getz, Joshua M. Stuart, David A. Wheeler, Lieven Verbeke, Abdullah Kahraman, Mark A. Rubin, Michael S. Lawrence, Alfonso Valencia, and Raunak Shrestha
Subjects: RNA Splicing Factors, Genetics, 0303 health sciences, Wnt signaling pathway, Cancer, Biology, medicine.disease, Genome, Chromatin remodeling, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, RNA splicing, Gene expression, medicine, Gene, 030304 developmental biology
Abstract: The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notablyTERTpromoter mutations, have been reported. Motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes, we performed multi-faceted pathway and network analyses of non-coding mutations across 2,583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project. While few non-coding genomic elements were recurrently mutated in this cohort, we identified 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression inTP53, TLE4, andTCF4. We found that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing was primarily targeted by non-coding mutations in this cohort, with samples containing non-coding mutations exhibiting similar gene expression signatures as coding mutations in well-known RNA splicing factors. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments.
Published: 2018

8. wKinMut-2: Identification and Interpretation of Pathogenic Variants in Human Protein Kinases

Author: Alfonso Valencia, Tirso Pons, Søren Brunak, Jose M. G. Izarzugaza, and Miguel Vazquez
Subjects: 0301 basic medicine, Genetics, Interpretation (logic), Kinase, Genomics, Computational biology, Plasma protein binding, Working hypothesis, Biology, Proto-Oncogene Proteins B-raf, 03 medical and health sciences, 030104 developmental biology, Identification (biology), Protein kinase A, Genetics (clinical)
Abstract: Most genomic alterations are tolerated while only a minor fraction disrupts molecular function sufficiently to drive disease. Protein kinases play a central biological function and the functional consequences of their variants are abundantly characterized. However, this heterogeneous information is often scattered across different sources, which makes the integrative analysis complex and laborious. wKinMut-2 constitutes a solution to facilitate the interpretation of the consequences of human protein kinase variation. Nine methods predict their pathogenicity, including a kinase-specific random forest approach. To understand the biological mechanisms causative of human diseases and cancer, information from pertinent reference knowledge bases and the literature is automatically mined, digested, and homogenized. Variants are visualized in their structural contexts and residues affecting catalytic and drug binding are identified. Known protein-protein interactions are reported. Altogether, this information is intended to assist the generation of new working hypothesis to be corroborated with ulterior experimental work. The wKinMut-2 system, along with a user manual and examples, is freely accessible at http://kinmut2.bioinfo.cnio.es, the code for local installations can be downloaded from https://github.com/Rbbt-Workflows/KinMut2.
Published: 2015

9. KinMutRF: a random forest classifier of sequence variants in the human protein kinase superfamily

Author: Maria Luisa Matey-Hernandez, Søren Brunak, Jose M. G. Izarzugaza, Miguel Vazquez, Tirso Pons, and Alfonso Valencia
Subjects: 0301 basic medicine, Protein family, X-linked agammaglobulinemia, Biology, Proteomics, medicine.disease_cause, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Protein kinases, medicine, Genetics, Functional impact, Humans, Protein kinase A, Databases, Protein, Gene, Mutation, Methodology Article, Variant prioritization, Decision Trees, Computational Biology, Genetic Variation, Random forest, 030104 developmental biology, DNA microarray, UniProt, Pathogenicity prediction, Software, Biotechnology
Abstract: Background The association between aberrant signal processing by protein kinases and human diseases such as cancer was established long time ago. However, understanding the link between sequence variants in the protein kinase superfamily and the mechanistic complex traits at the molecular level remains challenging: cells tolerate most genomic alterations and only a minor fraction disrupt molecular function sufficiently and drive disease. Results KinMutRF is a novel random-forest method to automatically identify pathogenic variants in human kinases. Twenty six decision trees implemented as a random forest ponder a battery of features that characterize the variants: a) at the gene level, including membership to a Kinbase group and Gene Ontology terms; b) at the PFAM domain level; and c) at the residue level, the types of amino acids involved, changes in biochemical properties, functional annotations from UniProt, Phospho.ELM and FireDB. KinMutRF identifies disease-associated variants satisfactorily (Acc: 0.88, Prec:0.82, Rec:0.75, F-score:0.78, MCC:0.68) when trained and cross-validated with the 3689 human kinase variants from UniProt that have been annotated as neutral or pathogenic. All unclassified variants were excluded from the training set. Furthermore, KinMutRF is discussed with respect to two independent kinase-specific sets of mutations no included in the training and testing, Kin-Driver (643 variants) and Pon-BTK (1495 variants). Moreover, we provide predictions for the 848 protein kinase variants in UniProt that remained unclassified. A public implementation of KinMutRF, including documentation and examples, is available online (http://kinmut2.bioinfo.cnio.es). The source code for local installation is released under a GPL version 3 license, and can be downloaded from https://github.com/Rbbt-Workflows/KinMut2. Conclusions KinMutRF is capable of classifying kinase variation with good performance. Predictions by KinMutRF compare favorably in a benchmark with other state-of-the-art methods (i.e. SIFT, Polyphen-2, MutationAssesor, MutationTaster, LRT, CADD, FATHMM, and VEST). Kinase-specific features rank as the most elucidatory in terms of information gain and are likely the improvement in prediction performance. This advocates for the development of family-specific classifiers able to exploit the discriminatory power of features unique to individual protein families. Electronic supplementary material The online version of this article (doi:10.1186/s12864-016-2723-1) contains supplementary material, which is available to authorized users.
Published: 2016

10. Identification of Known and Novel Recurrent Viral Sequences in Data from Multiple Patients and Multiple Cancers

Author: Helena Fridholm, Sarah Mollerup, Jens Friis-Nielsen, Pernille V. S. Olsen, Tobias Mourier, Stine Raith Richter, Eske Willerslev, David E. Alquezar-Planas, Maria Asplund, Thomas Sicheritz-Pontén, Thomas Arn Hansen, Ole Lund, Lars Peter Nielsen, Søren Brunak, Lasse Vinner, Jose M. G. Izarzugaza, Kristín Rós Kjartansdóttir, Randi Holm Jensen, Anders J. Hansen, Alba Rey-Iglesia, and Ida Broman Nielsen
Subjects: 0301 basic medicine, Taxonomic characterisation, oncoviruses, 030106 microbiology, lcsh:QR1-502, Sequence clustering, Assay contamination, Disease, Computational biology, Biology, Oncoviruses, Article, lcsh:Microbiology, DNA sequencing, Conserved sequence, sequence clustering, taxonomic characterisation, novel sequence identification, next generation sequencing, cancer causing viruses, assay contamination, 03 medical and health sciences, Annotation, SDG 3 - Good Health and Well-being, Neoplasms, Virology, Next generation sequencing, Journal Article, Humans, Conserved Sequence, Genetics, Novel sequence identification, Research Support, Non-U.S. Gov't, Computational Biology, High-Throughput Nucleotide Sequencing, 030104 developmental biology, Infectious Diseases, Viruses, Cancer causing viruses, RNA, Viral, Identification (biology), Sequence space (evolution), Oncovirus
Abstract: Virus discovery from high throughput sequencing data often follows a bottom-up approach where taxonomic annotation takes place prior to association to disease. Albeit effective in some cases, the approach fails to detect novel pathogens and remote variants not present in reference databases. We have developed a species independent pipeline that utilises sequence clustering for the identification of nucleotide sequences that co-occur across multiple sequencing data instances. We applied the workflow to 686 sequencing libraries from 252 cancer samples of different cancer and tissue types, 32 non-template controls, and 24 test samples. Recurrent sequences were statistically associated to biological, methodological or technical features with the aim to identify novel pathogens or plausible contaminants that may associate to a particular kit or method. We provide examples of identified inhabitants of the healthy tissue flora as well as experimental contaminants. Unmapped sequences that co-occur with high statistical significance potentially represent the unknown sequence space where novel pathogens can be identified.
Published: 2016

11. Cancer-associated mutations are preferentially distributed in protein kinase functional sites

Author: Oliver C. Redfern, Alfonso Valencia, Christine A. Orengo, and Jose M. G. Izarzugaza
Subjects: Genetics, education.field_of_study, Kinase, Point mutation, Population, Cancer, Biology, medicine.disease, Biochemistry, Retinoblastoma-like protein 1, Germline mutation, Structural Biology, medicine, Kinome, education, Protein kinase A, Molecular Biology
Abstract: Protein kinases are a superfamily involved in many crucial cellular processes, including signal transmission and regulation of cell cycle. As a consequence of this role, kinases have been reported to be associated with many types of cancer and are considered as potential therapeutic targets. We analyzed the distribution of pathogenic somatic point mutations (drivers) in the protein kinase superfamily with respect to their location in the protein, such as in structural, evolutionary, and functionally relevant regions. We find these driver mutations are more clearly associated with key protein features than other somatic mutations (passengers) that have not been directly linked to tumor progression. This observation fits well with the expected implication of the alterations in protein kinase function in cancer pathogenicity. To explain the relevance of the detected association of cancer driver mutations at the molecular level in the human kinome, we compare these with genetically inherited mutations (SNPs). We find that the subset of nonsynonymous SNPs that are associated to disease, but sufficiently mild to the point of being widespread in the population, tend to avoid those key protein regions, where they could be more detrimental for protein function. This tendency contrasts with the one detected for cancer associated-driver-mutations, which seems to be more directly implicated in the alteration of protein function. The detailed analysis of protein kinase groups and a number of relevant examples, confirm the relation between cancer associated-driver-mutations and key regions for protein kinase structure and function. Proteins 2009; 77:892-903. (C) 2009 Wiley-Liss, Inc.
Published: 2009

12. From cancer genomes to cancer models: bridging the gaps

Author: Alfonso Valencia, Anaïs Baudot, Jose M. G. Izarzugaza, and Francisco X. Real
Subjects: Genetics, Bridging (networking), Genetic variants, Computational Biology, Cancer, Genomics, Review Article, Experimental validation, Computational biology, Biology, medicine.disease, Models, Biological, Biochemistry, Genome, Neoplasms, Cancer genome, Cancer evolution, medicine, Humans, Computational analysis, Molecular Biology
Abstract: Cancer genome projects are now being expanded in an attempt to provide complete landscapes of the mutations that exist in tumours. Although the importance of cataloguing genome variations is well recognized, there are obvious difficulties in bridging the gaps between high-throughput resequencing information and the molecular mechanisms of cancer evolution. Here, we describe the current status of the high-throughput genomic technologies, and the current limitations of the associated computational analysis and experimental validation of cancer genetic variants. We emphasize how the current cancer-evolution models will be influenced by the high-throughput approaches, in particular through efforts devoted to monitoring tumour progression, and how, in turn, the integration of data and models will be translated into mechanistic knowledge and clinical applications.
Published: 2009

13. Traces of ATCV-1 associated with laboratory component contamination

Author: Anders J. Hansen, Jose M. G. Izarzugaza, Lars Peter Nielsen, Lasse Vinner, Kristín Rós Kjartansdóttir, Helena Fridholm, Tobias Mourier, David E. Alquezar-Planas, Sarah Mollerup, Maria Asplund, Eske Willerslev, Stine Raith Richter, Thomas Arn Hansen, Søren Brunak, Alba Rey-Iglesia, Jens Friis-Nielsen, Pernille V. S. Olsen, Thomas Sicheritz-Pontén, and Randi Holm Jensen
Subjects: Male, Chlorella, Moths, medicine.disease_cause, Genome, Virus, Cognition, Memory, medicine, Animals, Humans, Phycodnaviridae, Letters, Sequence (medicine), Genetics, Multidisciplinary, biology, Behavior, Animal, Contamination, biology.organism_classification, Freshwater algae, Female, Larynx, Acanthocystis turfacea Chlorella virus 1
Abstract: Yolken et al. (1) claim detection of Acanthocystis turfacea chlorella virus 1 (ATCV-1, gi119953744) in the normal human oropharyngeal viral flora and associate it with altered cognitive function. However, the reported presence of a freshwater algae virus, previously not known to infect other species, was based on a few sequence reads homologous to ATCV-1 identified with BLASTn. These reads span relatively few bases (97–698 bp) per sample, dispersed over a minor fraction (0.03–0.24%) of the 288 kb ATCV-1 genome.
Published: 2015

14. Investigation of Human Cancers for Retrovirus by Low-Stringency Target Enrichment and High-Throughput Sequencing

Author: Jens Friis-Nielsen, Ramneek Gupta, Tobias Mourier, Lasse Vinner, David Flores Santa Cruz, Jannik Fonager, Robert Gniadecki, Anders J. Hansen, Eske Willerslev, Søren Brunak, Jacob Rosenberg, Lars Peter Nielsen, Karen Dybkær, Jose M. G. Izarzugaza, Jill Levin Langhoff, and Thomas Sicheritz-Pontén
Subjects: Sus scrofa, Biology, Real-Time Polymerase Chain Reaction, Genome, DNA sequencing, Article, Retrovirus, SDG 3 - Good Health and Well-being, Proviruses, Neoplasms, medicine, Animals, Humans, Genomic library, RNA, Messenger, Gene Library, Genetics, Multidisciplinary, Base Sequence, Shotgun sequencing, Genome, Human, Hybridization probe, Cancer, High-Throughput Nucleotide Sequencing, medicine.disease, biology.organism_classification, HEK293 Cells, Retroviridae, DNA, Viral, HIV-1, Human genome, DNA Probes
Abstract: Although nearly one fifth of all human cancers have an infectious aetiology, the causes for the majority of cancers remain unexplained. Despite the enormous data output from high-throughput shotgun sequencing, viral DNA in a clinical sample typically constitutes a proportion of host DNA that is too small to be detected. Sequence variation among virus genomes complicates application of sequence-specific and highly sensitive, PCR methods. Therefore, we aimed to develop and characterize a method that permits sensitive detection of sequences despite considerable variation. We demonstrate that our low-stringency in-solution hybridization method enables detection of
Published: 2015

15. TSEMA: interactive prediction of protein pairings between interacting families

Author: Carles Pons, Juan A. G. Ranea, Florencio Pazos, Alfonso Valencia, David Juan, and Jose M. G. Izarzugaza
Subjects: Internet, Similarity (geometry), Theoretical computer science, Protein family, business.industry, Interface (Java), Heuristic, Monte Carlo method, Proteins, Biology, Bioinformatics, Article, User-Computer Interface, Software, Protein Interaction Mapping, Genetics, The Internet, business, Representation (mathematics), Monte Carlo Method, Phylogeny
Abstract: An entire family of methodologies for predicting protein interactions is based on the observed fact that families of interacting proteins tend to have similar phylogenetic trees due to co-evolution. One application of this concept is the prediction of the mapping between the members of two interacting protein families (which protein within one family interacts with which protein within the other). The idea is that the real mapping would be the one maximizing the similarity between the trees. Since the exhaustive exploration of all possible mappings is not feasible for large families, current approaches use heuristic techniques which do not ensure the best solution to be found. This is why it is important to check the results proposed by heuristic techniques and to manually explore other solutions. Here we present TSEMA, the server for efficient mapping assessment. This system calculates an initial mapping between two families of proteins based on a Monte Carlo approach and allows the user to interactively modify it based on performance figures and/or specific biological knowledge. All the explored mappings are graphically shown over a representation of the phylogenetic trees. The system is freely available at http://pdg.cnb.uam.es/TSEMA. Standalone versions of the software behind the interface are available upon request from the authors.
Published: 2006

16. Prediction of disease causing non-synonymous SNPs by the Artificial Neural Network Predictor NetDiseaseSNP

Author: Thomas Nordahl Petersen, Ramneek Gupta, Søren Brunak, Morten Bo Johansen, and Jose M. G. Izarzugaza
Subjects: Male, lcsh:Medicine, Disease, computer.software_genre, 0302 clinical medicine, Neoplasms, lcsh:Science, Conserved Sequence, Genetics, 0303 health sciences, Multidisciplinary, Artificial neural network, Systems Biology, Genomics, Functional Genomics, 030220 oncology & carcinogenesis, Mutation (genetic algorithm), Nonsynonymous snps, Female, Web service, Sequence Analysis, Algorithms, Research Article, Neutral mutation, Molecular Sequence Data, Sequence alignment, Biology, Machine learning, Polymorphism, Single Nucleotide, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Genetic Mutation, Cancer Genetics, Humans, Genetic Predisposition to Disease, 030304 developmental biology, Sequence (medicine), Base Sequence, business.industry, lcsh:R, Computational Biology, Human Genetics, Genetics of Disease, Mutation, lcsh:Q, Neural Networks, Computer, Artificial intelligence, business, Sequence Alignment, computer
Abstract: We have developed a sequence conservation-based artificial neural network predictor called NetDiseaseSNP which classifies nsSNPs as disease-causing or neutral. Our method uses the excellent alignment generation algorithm of SIFT to identify related sequences and a combination of 31 features assessing sequence conservation and the predicted surface accessibility to produce a single score which can be used to rank nsSNPs based on their potential to cause disease. NetDiseaseSNP classifies successfully disease-causing and neutral mutations. In addition, we show that NetDiseaseSNP discriminates cancer driver and passenger mutations satisfactorily. Our method outperforms other state-of-the-art methods on several disease/neutral datasets as well as on cancer driver/passenger mutation datasets and can thus be used to pinpoint and prioritize plausible disease candidates among nsSNPs for further investigation. NetDiseaseSNP is publicly available as an online tool as well as a web service: http://www.cbs.dtu.dk/services/NetDiseaseSNP.
Published: 2013

17. wKinMut: An integrated tool for the analysis and interpretation of mutations in human protein kinases

Author: Alfonso Valencia, Jose M. G. Izarzugaza, Angela del Pozo, and Miguel Vazquez
Subjects: Subfamily, Protein Data Bank (RCSB PDB), Information Storage and Retrieval, Context (language use), Biology, medicine.disease_cause, Biochemistry, Structural Biology, Predictive Value of Tests, medicine, Humans, Databases, Protein, Molecular Biology, Gene, Genetics, Mutation, Kinase, Protein Stability, Applied Mathematics, Computational Biology, Phenotype, Leukemia, Lymphocytic, Chronic, B-Cell, Computer Science Applications, ErbB Receptors, DNA microarray, Protein Kinases, Software
Abstract: Protein kinases are involved in relevant physiological functions and a broad number of mutations in this superfamily have been reported in the literature to affect protein function and stability. Unfortunately, the exploration of the consequences on the phenotypes of each individual mutation remains a considerable challenge. The wKinMut web-server offers direct prediction of the potential pathogenicity of the mutations from a number of methods, including our recently developed prediction method based on the combination of information from a range of diverse sources, including physicochemical properties and functional annotations from FireDB and Swissprot and kinase-specific characteristics such as the membership to specific kinase groups, the annotation with disease-associated GO terms or the occurrence of the mutation in PFAM domains, and the relevance of the residues in determining kinase subfamily specificity from S3Det. This predictor yields interesting results that compare favourably with other methods in the field when applied to protein kinases. Together with the predictions, wKinMut offers a number of integrated services for the analysis of mutations. These include: the classification of the kinase, information about associations of the kinase with other proteins extracted from iHop, the mapping of the mutations onto PDB structures, pathogenicity records from a number of databases and the classification of mutations in large-scale cancer studies. Importantly, wKinMut is connected with the SNP2L system that extracts mentions of mutations directly from the literature, and therefore increases the possibilities of finding interesting functional information associated to the studied mutations. wKinMut facilitates the exploration of the information available about individual mutations by integrating prediction approaches with the automatic extraction of information from the literature (text mining) and several state-of-the-art databases. wKinMut has been used during the last year for the analysis of the consequences of mutations in the context of a number of cancer genome projects, including the recent analysis of Chronic Lymphocytic Leukemia cases and is publicly available at http://wkinmut.bioinfo.cnio.es .
Published: 2013

18. Interpretation of the Consequences of Mutations in Protein Kinases: Combined Use of Bioinformatics and Text Mining

Author: Alfonso Valencia, Martin Krallinger, and Jose M. G. Izarzugaza
Subjects: pathogenicity prediction, kinase, Physiology, Context (language use), Review Article, text mining, Disease, Bioinformatics, medicine.disease_cause, Genome, lcsh:Physiology, literature mining, Protein structure, Physiology (medical), Medicine, Protein kinase A, Genetics, disease, Mutation, lcsh:QP1-981, business.industry, protein kinase, Phenotype, mutation, variation, business, Function (biology)
Abstract: Protein kinases play a crucial role in a plethora of significant physiological functions and a number of mutations in this superfamily have been reported in the literature to disrupt protein structure and/or function. Computational and experimental research aims to discover the mechanistic connection between mutations in protein kinases and disease with the final aim of predicting the consequences of mutations on protein function and the subsequent phenotypic alterations. In this article, we will review the possibilities and limitations of current computational methods for the prediction of the pathogenicity of mutations in the protein kinase superfamily. In particular we will focus on the problem of benchmarking the predictions with independent gold standard datasets. We will propose a pipeline for the curation of mutations automatically extracted from the literature. Since many of these mutations are not included in the databases that are commonly used to train the computational methods to predict the pathogenicity of protein kinase mutations we propose them to build a valuable gold standard dataset in the benchmarking of a number of these predictors. Finally, we will discuss how text mining approaches constitute a powerful tool for the interpretation of the consequences of mutations in the context of disease genome analysis with particular focus on cancer.
Published: 2012

19. Characterization of pathogenic germline mutations in human Protein Kinases

Author: Christine A. Orengo, Lisa E. M. Hopcroft, Anja Barešić, Andrew J. Martin, Jose M. G. Izarzugaza, and Alfonso Valencia
Subjects: Models, Molecular, Silent mutation, Protein family, Biology, lcsh:Computer applications to medicine. Medical informatics, Biochemistry, Germline mutation, Structural Biology, Neoplasms, Nuclear Receptor Subfamily 4, Group A, Member 2, Humans, Point Mutation, Protein kinase A, lcsh:QH301-705.5, Molecular Biology, Germ-Line Mutation, Genetics, Biotechnology in Biomedicine (natural science, biomedicine and healthcare, bioethics area, Kinase, Research, Applied Mathematics, Point mutation, Protein Structure, Tertiary, Computer Science Applications, lcsh:Biology (General), Protein kinase domain, lcsh:R858-859.7, Protein Kinases, SINGLE-NUCLEOTIDE POLYMORPHISMS, ACANTHOSIS NIGRICANS, GENETIC-VARIATION, CANCER GENOMES, DISEASE, RESOURCE, SEQUENCE, DATABASE, GENERATION, RESIDUES, Protein Binding, Signal Transduction, Neutral mutation
Abstract: Background\ud Protein Kinases are a superfamily of proteins involved in crucial cellular processes such as cell cycle regulation and signal transduction. Accordingly, they play an important role in cancer biology. To contribute to the study of the relation between kinases and disease we compared pathogenic mutations to neutral mutations as an extension to our previous analysis of cancer somatic mutations. First, we analyzed native and mutant proteins in terms of amino acid composition. Secondly, mutations were characterized according to their potential structural effects and finally, we assessed the location of the different classes of polymorphisms with respect to kinase-relevant positions in terms of subfamily specificity, conservation, accessibility and functional sites.\ud \ud Results\ud Pathogenic Protein Kinase mutations perturb essential aspects of protein function, including disruption of substrate binding and/or effector recognition at family-specific positions. Interestingly these mutations in Protein Kinases display a tendency to avoid structurally relevant positions, what represents a significant difference with respect to the average distribution of pathogenic mutations in other protein families.\ud \ud Conclusions\ud Disease-associated mutations display sound differences with respect to neutral mutations: several amino acids are specific of each mutation type, different structural properties characterize each class and the distribution of pathogenic mutations within the consensus structure of the Protein Kinase domain is substantially different to that for non-pathogenic mutations. This preferential distribution confirms previous observations about the functional and structural distribution of the controversial cancer driver and passenger somatic mutations and their use as a proxy for the study of the involvement of somatic mutations in cancer development.
Published: 2011

20. An integrated approach to the interpretation of Single Amino Acid Polymorphisms within the framework of CATH and Gene3D

Author: Andrew J. Martin, Lisa E. M. McMillan, Corin Yeats, Andrew B. Clegg, Anja Barešić, Christine A. Orengo, Jose M. G. Izarzugaza, and Alfonso Valencia
Subjects: Models, Molecular, Mutant, Information Storage and Retrieval, Computational biology, Biology, medicine.disease_cause, Biochemistry, Protein structure, Structural Biology, Genetic variation, medicine, Protein Data Bank, UniProt Accession, Single Amino Acid Polymorphism, Protein Data Bank Chain, Pathogenic Deviation, Databases, Protein, Molecular Biology, Gene, Sequence (medicine), Genetics, Internet, Mutation, Biotechnology in Biomedicine (natural science, biomedicine and healthcare, bioethics area, Research, Applied Mathematics, Proteins, computer.file_format, Protein Data Bank, Computer Science Applications, Phenotype, Amino Acid Substitution, DNA microarray, computer
Abstract: Background\ud The phenotypic effects of sequence variations in protein-coding regions come about primarily via their effects on the resulting structures, for example by disrupting active sites or affecting structural stability. In order better to understand the mechanisms behind known mutant phenotypes, and predict the effects of novel variations, biologists need tools to gauge the impacts of DNA mutations in terms of their structural manifestation. Although many mutations occur within domains whose structure has been solved, many more occur within genes whose protein products have not been structurally characterized.\ud \ud Results\ud Here we present 3DSim (3D Structural Implication of Mutations), a database and web application facilitating the localization and visualization of single amino acid polymorphisms (SAAPs) mapped to protein structures even where the structure of the protein of interest is unknown. The server displays information on 6514 point mutations, 4865 of them known to be associated with disease. These polymorphisms are drawn from SAAPdb, which aggregates data from various sources including dbSNP and several pathogenic mutation databases. While the SAAPdb interface displays mutations on known structures, 3DSim projects mutations onto known sequence domains in Gene3D. This resource contains sequences annotated with domains predicted to belong to structural families in the CATH database. Mappings between domain sequences in Gene3D and known structures in CATH are obtained using a MUSCLE alignment. 1210 three-dimensional structures corresponding to CATH structural domains are currently included in 3DSim; these domains are distributed across 396 CATH superfamilies, and provide a comprehensive overview of the distribution of mutations in structural space.\ud \ud Conclusion\ud The server is publicly available at http://3DSim.bioinfo.cnio.es/ webcite. In addition, the database containing the mapping between SAAPdb, Gene3D and CATH is available on request and most of the functionality is available through programmatic web service access.
Published: 2008

21. Enhancing the prediction of protein pairings between interacting families using orthology information

Author: Florencio Pazos, David Juan, Alfonso Valencia, Jose M. G. Izarzugaza, and Carles Pons
Subjects: Protein family, Bioinformatics, Sequence alignment, Computational biology, Plasma protein binding, Biology, Prediction methods, lcsh:Computer applications to medicine. Medical informatics, Biochemistry, Structural Biology, Yeasts, Similarity (psychology), Protein Interaction Mapping, Databases, Protein, Molecular Biology, lcsh:QH301-705.5, Organism, Genetics, Phylogenetic tree, Applied Mathematics, Proteins, Mappings, Computer Science Applications, Phylogenetic Trees, Protein families, lcsh:Biology (General), lcsh:R858-859.7, DNA microarray, Sequence Alignment, Algorithms, Forecasting, Information Systems, Protein Binding, Research Article
Abstract: The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2105/9/35., [Background] It has repeatedly been shown that interacting protein families tend to have similar phylogenetic trees. These similarities can be used to predicting the mapping between two families of interacting proteins (i.e. which proteins from one family interact with which members of the other). The correct mapping will be that which maximizes the similarity between the trees. The two families may eventually comprise orthologs and paralogs, if members of the two families are present in more than one organism. This fact can be exploited to restrict the possible mappings, simply by impeding links between proteins of different organisms. We present here an algorithm to predict the mapping between families of interacting proteins which is able to incorporate information regarding orthologues, or any other assignment of proteins to "classes" that may restrict possible mappings., [Results] For the first time in methods for predicting mappings, we have tested this new approach on a large number of interacting protein domains in order to statistically assess its performance. The method accurately predicts around 80% in the most favourable cases. We also analysed in detail the results of the method for a well defined case of interacting families, the sensor and kinase components of the Ntr-type two-component system, for which up to 98% of the pairings predicted by the method were correct., [Conclusion] Based on the well established relationship between tree similarity and interactions we developed a method for predicting the mapping between two interacting families using genomic information alone. The program is available through a web interface., This work was in part funded by the projects BIO2006-15318 and PIE 200620I240 from the Spanish Ministry for Education and Science, and the European Union Projects LSHG-CT-2004-503567 (GENEFUN), LSHG-CT-2003-503265 (BIOSAPIENS), LSHG-CT-2004-512092 (EMBRACE) and LSHG-CT-2004-503568 (COMBIO). Computer support was provided by the Barcelona Supercomputer Centre (BSC) through the project BCV-2006-4-0010.
Published: 2008

22. Prioritization of pathogenic mutations in the protein kinase superfamily

Author: Jose M. G. Izarzugaza, Alfonso Valencia, Angela del Pozo, and Miguel Vazquez
Subjects: Genetics, Support Vector Machine, Biology, Proteomics, Protein sequencing, Proceedings, Neoplasms, Mutation, Humans, Kinome, DNA microarray, UniProt, Protein kinase A, Databases, Protein, Gene, Classifier (UML), Protein Kinases, Biotechnology
Abstract: Most of the many mutations described in human protein kinases are tolerated without significant disruption of the corresponding structures or molecular functions, while some of them have been associated to a variety of human diseases, including cancer. In the last decade, a plethora of computational methods to predict the effect of missense single-nucleotide variants (SNVs) have been developed. Still, current high-throughput sequencing efforts and the concomitant need for massive interpretation of protein sequence variants will demand for more efficient and/or accurate computational methods in the forthcoming years. We present KinMut, a support vector machine (SVM) approach, to identify pathogenic mutations in the protein kinase superfamily. KinMut relays on a combination of sequence-derived features that describe mutations at different levels: (1) Gene level: membership to a specific group in Kinbase and the annotation with GO terms; (2) Domain level: annotated PFAM domains; and (3) Residue level: physicochemical features of amino acids, specificity determining positions, and functional annotations from SwissProt and FireDB. The system has been trained with the set of 3492 human kinase mutations in UniProt for which experimental validation of their pathogenic or neutral character exists. In addition, we discuss the relative importance of these independent properties and their combination for the development of a kinase-specific predictor. Finally, we compare KinMut with other state-of-the-art prediction methods. Family-specific features appear among the most discriminative information sources, which allow us to produce accurate results in a reliable and very simple way with minimal supervision. Our study aims to broaden the knowledge on the mechanisms by which mutations in the human kinome contribute to disease with a particular focus in cancer. The classifier as well as further documentation is available at http://kinmut.bioinfo.cnio.es/ .
Published: 2012

23. Extraction of human kinase mutations from literature, databases and genotyping studies

Author: Martin Krallinger, Jose M. G. Izarzugaza, Carlos Rodriguez-Penagos, and Alfonso Valencia
Subjects: Protein family, Genotype, Information Storage and Retrieval, Single-nucleotide polymorphism, Biology, computer.software_genre, Biochemistry, Annotation, Protein sequencing, Text mining, Structural Biology, Databases, Genetic, Humans, Molecular Biology, Genotyping, Genetics, Database, business.industry, Applied Mathematics, Research, Reproducibility of Results, Genomics, Sequence Analysis, DNA, Computer Science Applications, ErbB Receptors, Protein kinase domain, Mutation, DNA microarray, Periodicals as Topic, business, computer, Protein Kinases
Abstract: Background There is a considerable interest in characterizing the biological role of specific protein residue substitutions through mutagenesis experiments. Additionally, recent efforts related to the detection of disease-associated SNPs motivated both the manual annotation, as well as the automatic extraction, of naturally occurring sequence variations from the literature, especially for protein families that play a significant role in signaling processes such as kinases. Systematic integration and comparison of kinase mutation information from multiple sources, covering literature, manual annotation databases and large-scale experiments can result in a more comprehensive view of functional, structural and disease associated aspects of protein sequence variants. Previously published mutation extraction approaches did not sufficiently distinguish between two fundamentally different variation origin categories, namely natural occurring and induced mutations generated through in vitro experiments. Results We present a literature mining pipeline for the automatic extraction and disambiguation of single-point mutation mentions from both abstracts as well as full text articles, followed by a sequence validation check to link mutations to their corresponding kinase protein sequences. Each mutation is scored according to whether it corresponds to an induced mutation or a natural sequence variant. We were able to provide direct literature links for a considerable fraction of previously annotated kinase mutations, enabling thus more efficient interpretation of their biological characterization and experimental context. In order to test the capabilities of the presented pipeline, the mutations in the protein kinase domain of the kinase family were analyzed. Using our literature extraction system, we were able to recover a total of 643 mutations-protein associations from PubMed abstracts and 6,970 from a large collection of full text articles. When compared to state-of-the-art annotation databases and high throughput genotyping studies, the mutation mentions extracted from the literature overlap to a good extent with the existing knowledgebases, whereas the remaining mentions suggest new mutation records that were not previously annotated in the databases. Conclusion Using the proposed residue disambiguation and classification approach, we were able to differentiate between natural variant and mutagenesis types of mutations with an accuracy of 93.88. The resulting system is useful for constructing a Gold Standard set of mutations extracted from the literature by human experts with minimal manual curation effort, providing direct pointers to relevant evidence sentences. Our system is able to recover mutations from the literature that are not present in state-of-the-art databases. Human expert manual validation of a subset of the literature extracted mutations conducted on 100 mutations from PubMed abstracts highlights that almost three quarters (72%) of the extracted mutations turned out to be correct, and more than half of these had not been previously annotated in databases.
Published: 2009

24. Systems genetics analysis identifies calcium-signaling defects as novel cause of congenital heart disease

Author: Jose M. G. Izarzugaza, Sabrina G. Ellesøe, Canan Doganli, Natasja Spring Ehlers, Marlene D. Dalgaard, Enrique Audain, Gregor Dombrowsky, Karina Banasik, Alejandro Sifrim, Anna Wilsdon, Bernard Thienpont, Jeroen Breckpot, Marc Gewillig, Competence Network for Congenital Heart Defects, Germany, J. David Brook, Marc-Phillip Hitz, Lars A. Larsen, and Søren Brunak
Subjects: Congenital heart disease, Genetics, Whole exome sequencing, Developmental biology, Systems biology, Calcium signaling, Medicine, QH426-470
Abstract: Abstract Background Congenital heart disease (CHD) occurs in almost 1% of newborn children and is considered a multifactorial disorder. CHD may segregate in families due to significant contribution of genetic factors in the disease etiology. The aim of the study was to identify pathophysiological mechanisms in families segregating CHD. Methods We used whole exome sequencing to identify rare genetic variants in ninety consenting participants from 32 Danish families with recurrent CHD. We applied a systems biology approach to identify developmental mechanisms influenced by accumulation of rare variants. We used an independent cohort of 714 CHD cases and 4922 controls for replication and performed functional investigations using zebrafish as in vivo model. Results We identified 1785 genes, in which rare alleles were shared between affected individuals within a family. These genes were enriched for known cardiac developmental genes, and 218 of these genes were mutated in more than one family. Our analysis revealed a functional cluster, enriched for proteins with a known participation in calcium signaling. Replication in an independent cohort confirmed increased mutation burden of calcium-signaling genes in CHD patients. Functional investigation of zebrafish orthologues of ITPR1, PLCB2, and ADCY2 verified a role in cardiac development and suggests a combinatorial effect of inactivation of these genes. Conclusions The study identifies abnormal calcium signaling as a novel pathophysiological mechanism in human CHD and confirms the complex genetic architecture underlying CHD.
Published: 2020
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24 results on '"Jose M G Izarzugaza"'

1. Correction: Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease.

2. Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease.

3. Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease

4. Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

5. Systems genetics analysis identify calcium signalling defects as novel cause of congenital heart disease

6. Correction: Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease

7. Pathway and network analysis of more than 2,500 whole cancer genomes

8. wKinMut-2: Identification and Interpretation of Pathogenic Variants in Human Protein Kinases

9. KinMutRF: a random forest classifier of sequence variants in the human protein kinase superfamily

10. Identification of Known and Novel Recurrent Viral Sequences in Data from Multiple Patients and Multiple Cancers

11. Cancer-associated mutations are preferentially distributed in protein kinase functional sites

12. From cancer genomes to cancer models: bridging the gaps

13. Traces of ATCV-1 associated with laboratory component contamination

14. Investigation of Human Cancers for Retrovirus by Low-Stringency Target Enrichment and High-Throughput Sequencing

15. TSEMA: interactive prediction of protein pairings between interacting families

16. Prediction of disease causing non-synonymous SNPs by the Artificial Neural Network Predictor NetDiseaseSNP

17. wKinMut: An integrated tool for the analysis and interpretation of mutations in human protein kinases

18. Interpretation of the Consequences of Mutations in Protein Kinases: Combined Use of Bioinformatics and Text Mining

19. Characterization of pathogenic germline mutations in human Protein Kinases

20. An integrated approach to the interpretation of Single Amino Acid Polymorphisms within the framework of CATH and Gene3D

21. Enhancing the prediction of protein pairings between interacting families using orthology information

22. Prioritization of pathogenic mutations in the protein kinase superfamily

23. Extraction of human kinase mutations from literature, databases and genotyping studies

24. Systems genetics analysis identifies calcium-signaling defects as novel cause of congenital heart disease

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