s41467-019-13983-9.pdf (6.34 MB)
Integrative pathway enrichment analysis of multivariate omics data
journal contribution
posted on 2023-01-09, 10:44 authored by Marta Paczkowska, Jonathan Barenboim, Nardnisa Sintupisut, Natalie S Fox, Helen Zhu, Diala Abd-Rabbo, Miles W Mee, Paul C Boutros, Federico Abascal, Samirkumar B Amin, Gary D Bader, Rameen Beroukhim, Johanna Bertl, Keith A Boroevich, Søren Brunak, Peter J Campbell, Joana Carlevaro-Fita, Dimple Chakravarty, Calvin Wing Yiu Chan, Ken Chen, Jung Kyoon Choi, Jordi Deu-Pons, Priyanka Dhingra, Klev Diamanti, Lars Feuerbach, J Lynn Fink, Nuno A Fonseca, Joan Frigola, Carlo Gambacorti-Passerini, Dale W Garsed, Mark Gerstein, Gad Getz, Abel Gonzalez-Perez, Qianyun Guo, Ivo G Gut, David Haan, Mark P Hamilton, Nicholas J Haradhvala, Arif O Harmanci, Mohamed Helmy, Carl Herrmann, Julian M Hess, Asger Hobolth, Ermin Hodzic, Chen Hong, Henrik Hornshøj, Keren Isaev, Jose MG Izarzugaza, Rory Johnson, Todd A Johnson, Malene Juul, Randi Istrup Juul, Andre Kahles, Abdullah Kahraman, Manolis Kellis, Ekta Khurana, Jaegil Kim, Jong K Kim, Youngwook Kim, Jan Komorowski, Jan O Korbel, Sushant Kumar, Andrés Lanzós, Michael S Lawrence, Donghoon Lee, Kjong-Van Lehmann, Shantao Li, Xiaotong Li, Ziao Lin, Eric Minwei Liu, Lucas Lochovsky, Shaoke Lou, Tobias Madsen, Kathleen Marchal, Iñigo Martincorena, Alexander Martinez-Fundichely, Yosef E Maruvka, Patrick D McGillivray, William Meyerson, Ferran Muiños, Loris Mularoni, Hidewaki Nakagawa, Morten Muhlig Nielsen, Keunchil Park, Kiejung Park, Jakob Skou Pedersen, Oriol Pich, Tirso Pons, Sergio Pulido-Tamayo, Benjamin J Raphael, Iker Reyes-Salazar, Matthew A Reyna, Esther Rheinbay, Mark A Rubin, Carlota Rubio-Perez, Radhakrishnan Sabarinathan, S Cenk Sahinalp, Gordon Saksena, Leonidas Salichos, Chris Sander, Steven E Schumacher, Mark Shackleton, Ofer Shapira, Ciyue Shen, Raunak Shrestha, Shimin Shuai, Nikos Sidiropoulos, Lina Sieverling, Nasa Sinnott-Armstrong, Lincoln D Stein, Joshua M Stuart, David Tamborero, Grace Tiao, Tatsuhiko Tsunoda, Husen M Umer, Liis Uusküla-Reimand, Alfonso Valencia, Miguel Vazquez, Lieven PC Verbeke, Claes Wadelius, Lina Wadi, Jiayin Wang, Jonathan Warrell, Sebastian M Waszak, Joachim Weischenfeldt, David A Wheeler, Guanming Wu, Jun Yu, Jing Zhang, Xuanping Zhang, Yan Zhang, Zhongming Zhao, Lihua Zou, Christian von Mering, Jüri Reimand, Lauri A Aaltonen, 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, Brice Aminou, Ole Ammerpohl, Matthew J Anderson, Yeng Ang, Davide Antonello, Pavana Anur, 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 RR Aure, Philip Awadalla, Marta Aymerich, Adrian Baez-Ortega, Matthew H Bailey, Peter J Bailey, Miruna Balasundaram, Saianand Balu, Pratiti Bandopadhayay, Rosamonde E Banks, Stefano Barbi, Andrew P Barbour, Jill Barnholtz-Sloan, Hugh Barr, Elisabet Barrera, John Bartlett, Javier Bartolome, Claudio Bassi, Oliver F Bathe, Daniel Baumhoer, Prashant Bavi, Stephen B Baylin, Wojciech Bazant, Duncan Beardsmore, Timothy A Beck, Sam Behjati, Andreas Behren, Beifang Niu, Cindy Bell, Sergi Beltran, Christopher Benz, Andrew Berchuck, Anke K Bergmann, Erik N Bergstrom, Benjamin P Berman, Daniel M Berney, Stephan H Bernhart, Mario Berrios, Samantha Bersani, Miguel Betancourt, Vinayak Bhandari, Shriram G Bhosle, Andrew V Biankin, Matthias Bieg, 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, Ivan Borozan, Christoph Borst, Marcus Bosenberg, Mattia Bosio, Jacqueline Boultwood, Guillaume Bourque, G Steven Bova, David T Bowen, Reanne Bowlby, David DL 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, Timothy JC Bruxner, Alicia L Bruzos, Alex Buchanan, Ivo Buchhalter, Christiane Buchholz, Susan Bullman, Hazel Burke, Birgit Burkhardt, Kathleen H Burns, John Busanovich, Carlos D Bustamante, Adam P Butler, 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, Elias Campo, Cinzia Cantù, Shaolong Cao, Thomas E Carey, Rebecca Carlsen, Ivana Cataldo, Mario Cazzola, Jonathan Cebon, Robert Cerfolio, Dianne E Chadwick, Don Chalmers, 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, Wan Choi, Christine Chomienne, Zechen Chong, 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, Vincenzo Corbo, Matthew G Cordes, Stephen M Cordner, Isidro Cortés-Ciriano, Kyle Covington, 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, Noreen Dhalla, Neesha C Dhani, Rajiv Dhir, Anthony DiBiase, Li Ding, Shuai Ding, Huy Q Dinh, Luc Dirix, HarshaVardhan Doddapaneni, Nilgun Donmez, Michelle T Dow, Ronny Drapkin, Oliver Drechsel, Ruben M Drews, Serge Serge, Tim Dudderidge, Ana Dueso-Barroso, Andrew J Dunford, Michael Dunn, Lewis Jonathan Dursi, 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, Roland Eils, Adel El-Naggar, Matthew Eldridge, Kyle Ellrott, Serap Erkek, Georgia Escaramis, Shadrielle MG Espiritu, Xavier Estivill, Dariush Etemadmoghadam, Jorunn E Eyfjord, Bishoy M Faltas, Daiming Fan, Yu Fan, William C Faquin, Claudiu Farcas, Matteo Fassan, Aquila Fatima, Francesco Favero, Nodirjon Fayzullaev, Ina Felau, Sian Fereday, Martin L Ferguson, Vincent Ferretti, Matthew A Field, 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, Christopher S Foster, Michael Fraser, Scott Frazer, Milana Frenkel-Morgenstern, William Friedman, Catrina C Fronick, Akihiro Fujimoto, Masashi Fujita, Masashi Fukayama, Lucinda A Fulton, Robert S Fulton, Mayuko Furuta, P Andrew Futreal, Anja Füllgrabe, Stacey B Gabriel, Steven Gallinger, Jianjiong Gao, Shengjie Gao, Levi Garraway, Øystein Garred, Erik Garrison, Nils Gehlenborg, Josep LL Gelpi, Joshy George, Daniela S Gerhard, Clarissa Gerhauser, Jeffrey E Gershenwald, Moritz Gerstung, Mohammed Ghori, Ronald Ghossein, Nasra H Giama, Richard A Gibbs, Bob Gibson, Anthony J Gill, Pelvender Gill, Dilip D Giri, Dominik Glodzik, Vincent J Gnanapragasam, Maria Elisabeth Goebler, Mary J Goldman, Carmen Gomez, Santiago Gonzalez, 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, Manaswi Gupta, Shailja Gupta, Marta Gut, Jonathan Göke, Gavin Ha, Andrea Haake, Siegfried Haas, Kerstin Haase, James E HaberMulti-omics datasets represent distinct aspects of the central dogma of molecular biology. Such high-dimensional molecular profiles pose challenges to data interpretation and hypothesis generation. ActivePathways is an integrative method that discovers significantly enriched pathways across multiple datasets using statistical data fusion, rationalizes contributing evidence and highlights associated genes. As part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumor types, we integrated genes with coding and non-coding mutations and revealed frequently mutated pathways and additional cancer genes with infrequent mutations. We also analyzed prognostic molecular pathways by integrating genomic and transcriptomic features of 1780 breast cancers and highlighted associations with immune response and anti-apoptotic signaling. Integration of ChIP-seq and RNA-seq data for master regulators of the Hippo pathway across normal human tissues identified processes of tissue regeneration and stem cell regulation. ActivePathways is a versatile method that improves systems-level understanding of cellular organization in health and disease through integration of multiple molecular datasets and pathway annotations.
