About the Authors

Malachi Griffith

mgriffit@genome.wustl.edu (MG); ogriffit@genome.wustl.edu (OLG)

‡ These authors contributed equally and are listed in alphabetical order.

Affiliations The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America, Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, United States of America

Obi L. Griffith

mgriffit@genome.wustl.edu (MG); ogriffit@genome.wustl.edu (OLG)

‡ These authors contributed equally and are listed in alphabetical order.

Affiliations The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America

Scott M. Smith

Current address: Counsyl Inc., South San Francisco, United States of America

‡ These authors contributed equally and are listed in alphabetical order.

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Avinash Ramu

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Matthew B. Callaway

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Anthony M. Brummett

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Michael J. Kiwala

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Adam C. Coffman

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Allison A. Regier

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Ben J. Oberkfell

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Gabriel E. Sanderson

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Thomas P. Mooney

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Nathaniel G. Nutter

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Edward A. Belter

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Feiyu Du

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Robert L. Long

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Travis E. Abbott

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Ian T. Ferguson

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

David L. Morton

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Mark M. Burnett

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

James V. Weible

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Joshua B. Peck

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Adam Dukes

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Joshua F. McMichael

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Justin T. Lolofie

Current address: University of Hawaii at Manoa, Honolulu, Hawaii, United States of America

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Brian R. Derickson

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Jasreet Hundal

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Zachary L. Skidmore

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Benjamin J. Ainscough

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Nathan D. Dees

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

William S. Schierding

Current address: Liggins Institute, Auckland University, Auckland, New Zealand

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Cyriac Kandoth

Current address: Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Kyung H. Kim

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Charles Lu

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Christopher C. Harris

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Nicole Maher

Affiliation Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America

Christopher A. Maher

Affiliations The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America, Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri, United States of America

Vincent J. Magrini

Affiliations The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America, Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, United States of America

Benjamin S. Abbott

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Ken Chen

Current address: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Eric Clark

Current address: University of Illinois at Urbana-Champaign, Champaign, Illinois, United States of America

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Indraniel Das

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Xian Fan

Current address: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Amy E. Hawkins

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Todd G. Hepler

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Todd N. Wylie

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Shawn M. Leonard

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

William E. Schroeder

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Xiaoqi Shi

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Lynn K. Carmichael

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Matthew R. Weil

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Richard W. Wohlstadter

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Gary Stiehr

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Michael D. McLellan

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Craig S. Pohl

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Christopher A. Miller

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Daniel C. Koboldt

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Jason R. Walker

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

James M. Eldred

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

David E. Larson

Affiliations The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America, Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, United States of America

David J. Dooling

Current address: Monsanto Company, St. Louis, Missouri, United States of America

Affiliation The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America

Li Ding

Affiliations The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America, Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, United States of America, Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri, United States of America

Elaine R. Mardis

Affiliations The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America, Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, United States of America, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America, Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri, United States of America, Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America

Richard K. Wilson

Affiliations The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, United States of America, Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, United States of America, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America, Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri, United States of America, Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America

Competing Interests

The authors have declared that no competing interests exist.

Author Contributions

Conceived and designed the experiments: MG OLG SMS AMB BJO JRW JME DEL DJD LD ERM RKW. Performed the experiments: NM CAMa VJM. Analyzed the data: MG OLG SMS AAR ZLS BJA. Contributed reagents/materials/analysis tools: MG OLG SMS MBC AMB MJK ACC AAR BJO GES TPM NGN EAB FD RLL TEA ITF DLM MMB JVW JBP AD JFM JTL BRD JH NDD WSS CK KHK CL CCH NM CAMa BSA KC EC ID XF AEH TGH TNW SML WES XS LKC MRW RWW GS MDM CSP CAMi DCK JRW JME DEL DJD. Wrote the paper: SMS MG OLG DJD. SMS, JME, AMB, and BJO conceived of the original architecture, with input from DJD. JRW, GES, CCH, AD and EAB scaled the system up and TPM, NGN, AAR and BRD brought the core system to its current state. GS implemented processing profiles. CCH added the build tracking. The alignment API was developed by JRW, CCH, BJO, SMS, TPM, AD, ACC, GES and EAB. The variant detection API was designed by GS, RLL, TEA, AMB and SMS. Sequence transformation APIs were implemented by EAB, KHK, and FD. The workflow system was developed by EC, LKC, JRW, AMB, EAB, SMS, TEA, MMB, DLM, ACC and DEL. The annotation system was developed by XS, LD, MDM, GS, AD, EAB, JVW, AAR, SMS. The original somatic pipeline workflow was developed by DEL, DCK, NDD, CCH, GES, RLL, FD, BRD, MG, DEL, JVW, CAMi, and SMS. The validation system was developed by NDD, DCK, DEL, TPM and JVW. The GMS software was developed by TPM, GES, NGN, AAR, TEA, ITF, ACC, JVW, DLM, AD, DEL, MMB, CCH, XS, RLL, JBP, JFM, AMB, BJO, CAMi, EAB, TNW, BSA, CK, NDD, BJA, JRW, NGN, DCK, WSS, CAMa, KHK, KC, XF, FD, MBC, JME, JH, BRD, JTL, EC, AAR, MG, OLG and SMS, with contributions of LIMS integration from SML, CSP, TGH, ID, BSA and AEH. Cancer analysis processing profiles and tools were developed by MG, OLG, DEL, LD, MDM, JRW, DCK, NDD, CL, CAMi, CAMa, CCH, WSS, XS, JH, TNW, CK, MBC, KC, XF, GES, AAR, FD, SMS and BSA. Germline analysis processing profiles were developed by DEL, DCK, CL, WSS, TEA, CCH, RLL, and GES. Reference sequence code was written by EAB, KHK, TEA, and AAR. UR and App API were the work of SMS, AMB, TGH, DJD, CSP, JME, EC, NGN, BRD, TEA, BJO, ID, JRW and MBC. The sample and patient tracking was designed by SMS, CSP, LKC and BRD. The disk allocation system was developed by WES, MJK, TGH, AEH, BSA, ID, JTL, CSP, BRD, NGN, BJO, JVW and AMB. The web interface was developed by BJO, JTL, EC, JFM, ACC and BJO. The computational platform behind the GMS was developed by DJD, RWW, MBC, GS, MRW, NGN, EC, CSP, JFM, AMB, ACC, BRD and SMS. The system federation was developed by SMS. Installation testing and debugging was done by SMS, MG, OLG, ARa, ZLS, ARa and MJK.