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Deciphering the impact of genomic variation on function

  • Jesse M. Engreitz,
  • Heather A. Lawson,
  • Harinder Singh,
  • Lea M. Starita,
  • Gary C. Hon,
  • Hannah Carter,
  • Nidhi Sahni,
  • Timothy E. Reddy,
  • Xihong Lin,
  • Yun Li,
  • Nikhil V. Munshi,
  • Maria H. Chahrour,
  • Alan P. Boyle,
  • Benjamin C. Hitz,
  • Ali Mortazavi,
  • Mark Craven,
  • Karen L. Mohlke,
  • Luca Pinello,
  • Ting Wang,
  • Anshul Kundaje,
  • Feng Yue,
  • Sarah Cody,
  • Nina P. Farrell,
  • Michael I. Love,
  • Lara A. Muffley,
  • Michael J. Pazin,
  • Fairlie Reese,
  • Eric Van Buren,
  • Kushal K. Dey,
  • Martin Kircher,
  • Jian Ma,
  • Predrag Radivojac,
  • Brunilda Balliu,
  • Brian A. Williams,
  • Danwei Huangfu,
  • Chong Y. Park,
  • Thomas Quertermous,
  • Jishnu Das,
  • Michael A. Calderwood,
  • Douglas M. Fowler,
  • Marc Vidal,
  • Lucas Ferreira,
  • Sean D. Mooney,
  • Vikas Pejaver,
  • Jingjing Zhao,
  • Steven Gazal,
  • Evan Koch,
  • Steven K. Reilly,
  • Shamil Sunyaev,
  • Anne E. Carpenter,
  • Jason D. Buenrostro,
  • Christina S. Leslie,
  • Rachel E. Savage,
  • Stefanija Giric,
  • Chongyuan Luo,
  • Kathrin Plath,
  • Alejandro Barrera,
  • Max Schubach,
  • Andreas R. Gschwind,
  • Jill E. Moore,
  • Nadav Ahituv,
  • S. Stephen Yi,
  • Ingileif Hallgrimsdottir,
  • Kyle J. Gaulton,
  • Saori Sakaue,
  • Sina Booeshaghi,
  • Eugenio Mattei,
  • Surag Nair,
  • Lior Pachter,
  • Austin T. Wang,
  • Jay Shendure,
  • Vikram Agarwal,
  • Andrew Blair,
  • Theofilos Chalkiadakis,
  • Florence M. Chardon,
  • Pyaree M. Dash,
  • Chengyu Deng,
  • Nobuhiko Hamazaki,
  • Pia Keukeleire,
  • Connor Kubo,
  • Jean-Benoît Lalanne,
  • Thorben Maass,
  • Beth Martin,
  • Troy A. McDiarmid,
  • Mai Nobuhara,
  • Nicholas F. Page,
  • Sam Regalado,
  • Jasmine Sims,
  • Aki Ushiki,
  • Sabrina M. Best,
  • Gabe Boyle,
  • Nathan Camp,
  • Silvia Casadei,
  • Estelle Y. Da,
  • Moez Dawood,
  • Samantha C. Dawson,
  • Shawn Fayer,
  • Audrey Hamm,
  • Richard G. James,
  • Gail P. Jarvik,
  • Abbye E. McEwen,
  • Nick Moore,
  • Sriram Pendyala,
  • Nicholas A. Popp,
  • Mason Post,
  • Alan F. Rubin,
  • Nahum T. Smith,
  • Jeremy Stone,
  • Malvika Tejura,
  • Ziyu R. Wang,
  • Melinda K. Wheelock,
  • Ivan Woo,
  • Brendan D. Zapp,
  • Dulguun Amgalan,
  • Aradhana Aradhana,
  • Sophia M. Arana,
  • Michael C. Bassik,
  • Julia R. Bauman,
  • Asmita Bhattacharya,
  • Xiangmeng Shawn Cai,
  • Ziwei Chen,
  • Stephanie Conley,
  • Salil Deshpande,
  • Benjamin R. Doughty,
  • Peter P. Du,
  • James A. Galante,
  • Casey Gifford,
  • William J. Greenleaf,
  • Katherine Guo,
  • Revant Gupta,
  • Sarasa Isobe,
  • Evelyn Jagoda,
  • Nimit Jain,
  • Hank Jones,
  • Helen Y. Kang,
  • Samuel H. Kim,
  • YeEun Kim,
  • Sandy Klemm,
  • Ramen Kundu,
  • Soumya Kundu,
  • Mauro Lago-Docampo,
  • Yannick C. Lee-Yow,
  • Roni Levin-Konigsberg,
  • Daniel Y. Li,
  • Dominik Lindenhofer,
  • X. Rosa Ma,
  • Georgi K. Marinov,
  • Gabriella E. Martyn,
  • Chloe V. McCreery,
  • Eyal Metzl-Raz,
  • Joao P. Monteiro,
  • Michael T. Montgomery,
  • Kristy S. Mualim,
  • Chad Munger,
  • Glen Munson,
  • Tri C. Nguyen,
  • Trieu Nguyen,
  • Brian T. Palmisano,
  • Anusri Pampari,
  • Marlene Rabinovitch,
  • Markus Ramste,
  • Judhajeet Ray,
  • Kevin R. Roy,
  • Oriane M. Rubio,
  • Julia M. Schaepe,
  • Gavin Schnitzler,
  • Jacob Schreiber,
  • Disha Sharma,
  • Maya U. Sheth,
  • Huitong Shi,
  • Vasundhara Singh,
  • Riya Sinha,
  • Lars M. Steinmetz,
  • Jason Tan,
  • Anthony Tan,
  • Josh Tycko,
  • Raeline C. Valbuena,
  • Valeh Valiollah Pour Amiri,
  • Mariëlle J. F. M. van Kooten,
  • Alun Vaughan-Jackson,
  • Anthony Venida,
  • Chad S. Weldy,
  • Matthew D. Worssam,
  • Fan Xia,
  • David Yao,
  • Tony Zeng,
  • Quanyi Zhao,
  • Ronghao Zhou,
  • Zitong Sam Chen,
  • Beth A. Cimini,
  • Georges Coppin,
  • Atina G. Coté,
  • Marzieh Haghighi,
  • Tong Hao,
  • David E. Hill,
  • Jessica Lacoste,
  • Florent Laval,
  • Chloe Reno,
  • Frederick P. Roth,
  • Shantanu Singh,
  • Kerstin Spirohn-Fitzgerald,
  • Mikko Taipale,
  • Tanisha Teelucksingh,
  • Maxime Tixhon,
  • Anupama Yadav,
  • Zhipeng Yang,
  • W. Lee Kraus,
  • Daniel A. Armendariz,
  • Ashley E. Dederich,
  • Ashlesha Gogate,
  • Lauretta El Hayek,
  • Sean C. Goetsch,
  • Kiran Kaur,
  • Hyung Bum Kim,
  • Melissa K. McCoy,
  • Mpathi Z. Nzima,
  • Carlos A. Pinzón-Arteaga,
  • Bruce A. Posner,
  • Daniel A. Schmitz,
  • Sushama Sivakumar,
  • Anjana Sundarrajan,
  • Lei Wang,
  • Yihan Wang,
  • Jun Wu,
  • Lin Xu,
  • Jian Xu,
  • Leqian Yu,
  • Yanfeng Zhang,
  • Huan Zhao,
  • Qinbo Zhou,
  • Hyejung Won,
  • Jessica L. Bell,
  • K. Alaine Broadaway,
  • Katherine N. Degner,
  • Amy S. Etheridge,
  • Beverly H. Koller,
  • Won Mah,
  • Wancen Mu,
  • Kimberly D. Ritola,
  • Jonathan D. Rosen,
  • Sarah A. Schoenrock,
  • Rachel A. Sharp,
  • Daniel Bauer,
  • Guillaume Lettre,
  • Richard Sherwood,
  • Basheer Becerra,
  • Logan J. Blaine,
  • Eric Che,
  • Matthew J. Francoeur,
  • Ellie N. Gibbs,
  • Nahye Kim,
  • Emily M. King,
  • Benjamin P. Kleinstiver,
  • Estelle Lecluze,
  • Zhijian Li,
  • Zain M. Patel,
  • Quang Vinh Phan,
  • Jayoung Ryu,
  • Marlena L. Starr,
  • Ting Wu,
  • Charles A. Gersbach,
  • Gregory E. Crawford,
  • Andrew S. Allen,
  • William H. Majoros,
  • Nahid Iglesias,
  • Ruhi Rai,
  • Revathy Venukuttan,
  • Boxun Li,
  • Taylor Anglen,
  • Lexi R. Bounds,
  • Marisa C. Hamilton,
  • Siyan Liu,
  • Sean R. McCutcheon,
  • Christian D. McRoberts Amador,
  • Samuel J. Reisman,
  • Maria A. ter Weele,
  • Josephine C. Bodle,
  • Helen L. Streff,
  • Keith Siklenka,
  • Kari Strouse,
  • Bradley E. Bernstein,
  • Juliana Babu,
  • Guillermo Barreto Corona,
  • Kevin Dong,
  • Fabiana M. Duarte,
  • Neva C. Durand,
  • Charles B. Epstein,
  • Kaili Fan,
  • Elizabeth Gaskell,
  • Amelia W. Hall,
  • Alexandra M. Ham,
  • Mei K. Knudson,
  • Noam Shoresh,
  • Siddarth Wekhande,
  • Cassandra M. White,
  • Wang Xi,
  • Ansuman T. Satpathy,
  • M. Ryan Corces,
  • Serena H. Chang,
  • Iris M. Chin,
  • James M. Gardner,
  • Zachary A. Gardell,
  • Jacob C. Gutierrez,
  • Alia W. Johnson,
  • Lucas Kampman,
  • Maya Kasowski,
  • Caleb A. Lareau,
  • Vincent Liu,
  • Leif S. Ludwig,
  • Christopher S. McGinnis,
  • Shreya Menon,
  • Anita Qualls,
  • Katalin Sandor,
  • Adam W. Turner,
  • Chun J. Ye,
  • Yajie Yin,
  • Wenxi Zhang,
  • Barbara J. Wold,
  • Maria Carilli,
  • Dayeon Cheong,
  • Ghassan Filibam,
  • Kim Green,
  • Shimako Kawauchi,
  • Charlene Kim,
  • Heidi Liang,
  • Rebekah Loving,
  • Laura Luebbert,
  • Grant MacGregor,
  • Angel G. Merchan,
  • Elisabeth Rebboah,
  • Narges Rezaie,
  • Jasmine Sakr,
  • Delaney K. Sullivan,
  • Nikki Swarna,
  • Diane Trout,
  • Sean Upchurch,
  • Ryan Weber,
  • Christopher P. Castro,
  • Elysia Chou,
  • Fan Feng,
  • Andre Guerra,
  • Yuanhao Huang,
  • Linghua Jiang,
  • Jie Liu,
  • Ryan E. Mills,
  • Weizhou Qian,
  • Tingting Qin,
  • Maureen A. Sartor,
  • Rintsen N. Sherpa,
  • Jinhao Wang,
  • Yiqun Wang,
  • Joshua D. Welch,
  • Zhenhao Zhang,
  • Nanxiang Zhao,
  • Sayan Mukherjee,
  • C. David Page,
  • Shannon Clarke,
  • Richard W. Doty,
  • Yuncheng Duan,
  • Raluca Gordan,
  • Kuei-Yueh Ko,
  • Shengyu Li,
  • Boyao Li,
  • Alexander Thomson,
  • Soumya Raychaudhuri,
  • Alkes Price,
  • Thahmina A. Ali,
  • Kushal K. Dey,
  • Arun Durvasula,
  • Manolis Kellis,
  • Lilia M. Iakoucheva,
  • Tulika Kakati,
  • Yile Chen,
  • Mariam Benazouz,
  • Shantanu Jain,
  • Daniel Zeiberg,
  • M. Clara De Paolis Kaluza,
  • Michelle Velyunskiy,
  • Audrey Gasch,
  • Kunling Huang,
  • Yiyang Jin,
  • Qiongshi Lu,
  • Jiacheng Miao,
  • Michael Ohtake,
  • Eduardo Scopel,
  • Robert D. Steiner,
  • Yuriy Sverchkov,
  • Zhiping Weng,
  • Manuel Garber,
  • Yu Fu,
  • Natalie Haas,
  • Xihao Li,
  • Nishigandha Phalke,
  • Shuo C. Shan,
  • Nicole Shedd,
  • Tianxiong Yu,
  • Yi Zhang,
  • Hufeng Zhou,
  • Alexis Battle,
  • Livnat Jerby,
  • Eran Kotler,
  • Soumya Kundu,
  • Andrew R. Marderstein,
  • Stephen B. Montgomery,
  • AkshatKumar Nigam,
  • Evin M. Padhi,
  • Aman Patel,
  • Jonathan Pritchard,
  • Ivy Raine,
  • Vivekanandan Ramalingam,
  • Kameron B. Rodrigues,
  • Jacob M. Schreiber,
  • Arpita Singhal,
  • Riya Sinha,
  • Austin T. Wang,
  • Marisa Abundis,
  • Deepa Bisht,
  • Trirupa Chakraborty,
  • Jingyu Fan,
  • David R. Hall,
  • Zarifeh H. Rarani,
  • Abhinav K. Jain,
  • Babita Kaundal,
  • Swapnil Keshari,
  • Daniel McGrail,
  • Nicholas A. Pease,
  • Vivian F. Yi,
  • Hao Wu,
  • Sreeram Kannan,
  • Hongjun Song,
  • Jingli Cai,
  • Ziyue Gao,
  • Ronni Kurzion,
  • Julia I. Leu,
  • Fan Li,
  • Dongming Liang,
  • Guo-li Ming,
  • Kiran Musunuru,
  • Qi Qiu,
  • Junwei Shi,
  • Yijing Su,
  • Sarah Tishkoff,
  • Ning Xie,
  • Qian Yang,
  • Wenli Yang,
  • Hongjie Zhang,
  • Zhijian Zhang,
  • Michael A. Beer,
  • Anna-Katerina Hadjantonakis,
  • Sharon Adeniyi,
  • Hyein Cho,
  • Ronald Cutler,
  • Rachel A. Glenn,
  • David Godovich,
  • Nan Hu,
  • Svetlana Jovanic,
  • Renhe Luo,
  • Jin Woo Oh,
  • Milad Razavi-Mohseni,
  • Dustin Shigaki,
  • Simone Sidoli,
  • Thomas Vierbuchen,
  • Xianming Wang,
  • Breanna Williams,
  • Jielin Yan,
  • Dapeng Yang,
  • Yunxiao Yang,
  • Maike Sander,
  • Kyle J. Gaulton,
  • Bing Ren,
  • Weronika Bartosik,
  • Hannah S. Indralingam,
  • Adam Klie,
  • Hannah Mummey,
  • Mei-Lin Okino,
  • Gaowei Wang,
  • Nathan R. Zemke,
  • Kai Zhang,
  • Han Zhu,
  • Noah Zaitlen,
  • Jason Ernst,
  • Justin Langerman,
  • Terence Li,
  • Yu Sun,
  • Alexander Y. Rudensky,
  • Preethi K. Periyakoil,
  • Vianne R. Gao,
  • Melanie H. Smith,
  • Norman M. Thomas,
  • Laura T. Donlin,
  • Amit Lakhanpal,
  • Kaden M. Southard,
  • Rico C. Ardy,
  • J. Michael Cherry,
  • Mark B. Gerstein,
  • Kalina Andreeva,
  • Pedro R. Assis,
  • Beatrice Borsari,
  • Eric Douglass,
  • Shengcheng Dong,
  • Idan Gabdank,
  • Keenan Graham,
  • Otto Jolanki,
  • Jennifer Jou,
  • Meenakshi S. Kagda,
  • Jin-Wook Lee,
  • Mingjie Li,
  • Khine Lin,
  • Stuart R. Miyasato,
  • Joel Rozowsky,
  • Corinn Small,
  • Emma Spragins,
  • Forrest Y. Tanaka,
  • Ian M. Whaling,
  • Ingrid A. Youngworth,
  • Cricket A. Sloan,
  • Eddie Belter,
  • Xintong Chen,
  • Rex L. Chisholm,
  • Patricia Dickson,
  • Changxu Fan,
  • Lucinda Fulton,
  • Daofeng Li,
  • Tina Lindsay,
  • Yu Luan,
  • Yuan Luo,
  • Huijue Lyu,
  • Xiaowen Ma,
  • Juan Macias-Velasco,
  • Karen H. Miga,
  • Kara Quaid,
  • Nathan Stitziel,
  • Barbara E. Stranger,
  • Chad Tomlinson,
  • Juan Wang,
  • Wenjin Zhang,
  • Bo Zhang,
  • Guoyan Zhao,
  • Xiaoyu Zhuo,
  • Kristen Brennand,
  • Alberto Ciccia,
  • Samuel B. Hayward,
  • Jen-Wei Huang,
  • Giuseppe Leuzzi,
  • Angelo Taglialatela,
  • Tanay Thakar,
  • Alina Vaitsiankova,
  • Kushal K. Dey,
  • Thahmina A. Ali,
  • Artem Kim,
  • H. Leighton Grimes,
  • Nathan Salomonis,
  • Rajat Gupta,
  • Shi Fang,
  • Vivian Lee-Kim,
  • Matthias Heinig,
  • Corinna Losert,
  • Thouis R. Jones,
  • Elisa Donnard,
  • Maddie Murphy,
  • Elizabeth Roberts,
  • Susie Song,
  • Sara Mostafavi,
  • Alexander Sasse,
  • Anna Spiro,
  • Len A. Pennacchio,
  • Momoe Kato,
  • Michael Kosicki,
  • Brandon Mannion,
  • Neil Slaven,
  • Axel Visel,
  • Katherine S. Pollard,
  • Shiron Drusinsky,
  • Sean Whalen,
  • John Ray,
  • Ingrid A. Harten,
  • Ching-Huang Ho,
  • Neville E. Sanjana,
  • Christina Caragine,
  • John A. Morris,
  • Davide Seruggia,
  • Ana Patricia Kutschat,
  • Sandra Wittibschlager,
  • Han Xu,
  • Rongjie Fu,
  • Wei He,
  • Liang Zhang,
  • Daniel Osorio,
  • Zo Bly,
  • Stephanie Calluori,
  • Daniel A. Gilchrist,
  • Carolyn M. Hutter,
  • Stephanie A. Morris,
  • Ella K. Samer

摘要

Our genomes influence nearly every aspect of human biology—from molecular and cellular functions to phenotypes in health and disease. Studying the differences in DNA sequence between individuals (genomic variation) could reveal previously unknown mechanisms of human biology, uncover the basis of genetic predispositions to diseases, and guide the development of new diagnostic tools and therapeutic agents. Yet, understanding how genomic variation alters genome function to influence phenotype has proved challenging. To unlock these insights, we need a systematic and comprehensive catalogue of genome function and the molecular and cellular effects of genomic variants. Towards this goal, the Impact of Genomic Variation on Function (IGVF) Consortium will combine approaches in single-cell mapping, genomic perturbations and predictive modelling to investigate the relationships among genomic variation, genome function and phenotypes. IGVF will create maps across hundreds of cell types and states describing how coding variants alter protein activity, how noncoding variants change the regulation of gene expression, and how such effects connect through gene-regulatory and protein-interaction networks. These experimental data, computational predictions and accompanying standards and pipelines will be integrated into an open resource that will catalyse community efforts to explore how our genomes influence biology and disease across populations.