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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

Catherine A Brownstein1, Alan H Beggs1*, Nils Homer2, Barry Merriman3, Timothy W Yu1, Katherine C Flannery4, Elizabeth T DeChene1, Meghan C Towne1, Sarah K Savage1, Emily N Price1, Ingrid A Holm1, Lovelace J Luquette4, Elaine Lyon5, Joseph Majzoub6, Peter Neupert7, David McCallie Jr8, Peter Szolovits9, Huntington F Willard10, Nancy J Mendelsohn11, Renee Temme11, Richard S Finkel12, Sabrina W Yum13, Livija Medne14, Shamil R Sunyaev15, Ivan Adzhubey15, Christopher A Cassa15, Paul IW de Bakker1516, Hatice Duzkale17, Piotr Dworzyński18, William Fairbrother19, Laurent Francioli16, Birgit H Funke17, Monica A Giovanni15, Robert E Handsaker20, Kasper Lage21, Matthew S Lebo17, Monkol Lek22, Ignaty Leshchiner1517, Daniel G MacArthur22, Heather M McLaughlin17, Michael F Murray15, Tune H Pers23, Paz P Polak15, Soumya Raychaudhuri15, Heidi L Rehm17, Rachel Soemedi19, Nathan O Stitziel15, Sara Vestecka15, Jochen Supper2425, Claudia Gugenmus24, Bernward Klocke24, Alexander Hahn24, Max Schubach25, Mortiz Menzel25, Saskia Biskup25, Peter Freisinger2526, Mario Deng27, Martin Braun27, Sven Perner27, Richard JH Smith28, Janeen L Andorf28, Jian Huang29, Kelli Ryckman30, Val C Sheffield2831, Edwin M Stone2831, Thomas Bair28, E Ann Black-Ziegelbein28, Terry A Braun32, Benjamin Darbro28, Adam P DeLuca28, Diana L Kolbe28, Todd E Scheetz28, Aiden E Shearer28, Rama Sompallae28, Kai Wang33, Alexander G Bassuk28, Erik Edens28, Katherine Mathews28, Steven A Moore28, Oleg A Shchelochkov28, Pamela Trapane28, Aaron Bossler28, Colleen A Campbell28, Jonathan W Heusel28, Anne Kwitek28, Tara Maga28, Karin Panzer28, Thomas Wassink28, Douglas Van Daele28, Hela Azaiez28, Kevin Booth28, Nic Meyer28, Michael M Segal34, Marc S Williams35, Gerard Tromp35, Peter White36, Donald Corsmeier36, Sara Fitzgerald-Butt36, Gail Herman36, Devon Lamb-Thrush36, Kim L McBride36, David Newsom36, Christopher R Pierson36, Alexander T Rakowsky36, Aleš Maver37, Luca Lovrečić37, Anja Palandačić3794, Borut Peterlin37, Ali Torkamani38, Anna Wedell394041, Mikael Huss42, Andrey Alexeyenko43, Jessica M Lindvall44, Måns Magnusson394041, Daniel Nilsson394145, Henrik Stranneheim394041, Fulya Taylan3941, Christian Gilissen46, Alexander Hoischen46, Bregje van Bon46, Helger Yntema46, Marcel Nelen46, Weidong Zhang47, Jason Sager47, Lu Zhang48, Kathryn Blair48, Deniz Kural48, Michael Cariaso49, Greg G Lennon49, Asif Javed50, Saloni Agrawal50, Pauline C Ng50, Komal S Sandhu51, Shuba Krishna51, Vamsi Veeramachaneni51, Ofer Isakov52, Eran Halperin52, Eitan Friedman52, Noam Shomron52, Gustavo Glusman53, Jared C Roach53, Juan Caballero53, Hannah C Cox53, Denise Mauldin53, Seth A Ament53, Lee Rowen53, Daniel R Richards54, F Anthony San Lucas55, Manuel L Gonzalez-Garay56, C Thomas Caskey57, Yu Bai58, Ying Huang58, Fang Fang59, Yan Zhang60, Zhengyuan Wang60, Jorge Barrera61626364, Juan M Garcia-Lobo6162636465, Domingo González-Lamuño6667, Javier Llorca636869, Maria C Rodriguez61626364, Ignacio Varela61626364, Martin G Reese70, Francisco M De La Vega7071, Edward Kiruluta70, Michele Cargill72, Reece K Hart72, Jon M Sorenson72, Gholson J Lyon7374, David A Stevenson75, Bruce E Bray76, Barry M Moore7778, Karen Eilbeck78, Mark Yandell77, Hongyu Zhao79, Lin Hou79, Xiaowei Chen80, Xiting Yan81, Mengjie Chen80, Cong Li80, Can Yang79, Murat Gunel82, Peining Li83, Yong Kong84, Austin C Alexander85, Zayed I Albertyn86, Kym M Boycott87, Dennis E Bulman87, Paul MK Gordon88, A Micheil Innes89, Bartha M Knoppers90, Jacek Majewski91, Christian R Marshall92, Jillian S Parboosingh89, Sarah L Sawyer87, Mark E Samuels93, Jeremy Schwartzentruber91, Isaac S Kohane4* and David M Margulies1*

Author Affiliations

1 Division of Genetics and Genomics, The Research Connection and The Manton Center for Orphan Disease Research, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA

2 Claritas Genomics, Boston, MA, USA

3 Life Technologies, Carlsbad, CA, USA

4 Center for Biomedical Informatics, Harvard Medical School, Boston, MA, USA

5 University of Utah School of Medicine, ARUP Laboratories, Salt Lake City, UT, USA

6 Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA

7 Microsoft Health Solutions Group, Microsoft Corporation, Seattle, WA, USA

8 Medical Informatics, Cerner Corporation, Kansas City, MO, USA

9 Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA

10 Duke Institute for Genome Sciences & Policy, Duke University, Durham, NC, USA

11 Department of Medical Genetics, Children’s Hospitals and Clinics of Minnesota, Minneapolis, MN, USA

12 Division of Neurology, Nemours Children's Hospital, Orlando, FL, USA

13 Division of Neurology, Children’s Hospital of Philadelphia, and Department of Neurology, Perelmen School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

14 Division of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

15 Division of Genetics, Brigham and Woman’s Hospital, Harvard Medical School, Boston, MA, USA

16 Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands

17 Laboratory for Molecular Medicine, Partners Healthcare Center for Personalized Genetic Medicine, Brigham and Woman’s Hospital, Harvard Medical School, Boston, MA, USA

18 Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark

19 Center for Computational Molecular Biology, Brown University, Providence, RI, USA

20 Department of Genetics, Harvard Medical School, Boston, MA, USA

21 Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

22 Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

23 Division of Endocrinology and Center for Basic and Translational Obesity Research, Children’s Hospital Boston, Boston, MA, USA

24 Genomatix Software GmbH, Bayerstr 85a, Munich, Germany

25 CeGaT GmbH, Paul-Ehrlich-Str. 17, Tübingen, Germany

26 Children's Hospital Reutlingen, Reutlingen, Germany

27 Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Bonn, Germany

28 Iowa Institute of Human Genetics, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA

29 Iowa Institute of Human Genetics, College of Liberal Arts and Sciences, The University of Iowa, Iowa City, IA, USA

30 Iowa Institute of Human Genetics, Department of Epidemiology, College of Public Health, The University of Iowa, Iowa City, IA, USA

31 Howard Hughes Medical Institute, University of Iowa, Iowa City, IA, USA

32 Iowa Institute of Human Genetics, College of Engineering, The University of Iowa, Iowa City, IA, USA

33 Iowa Institute of Human Genetics, Department of Biostatistics, College of Public Health, The University of Iowa, Iowa City, IA, USA

34 SimulConsult, Chestnut Hill, MA, USA

35 Geisinger Health System, Danville, PA, USA

36 Nationwide Children’s Hospital, Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA

37 Clinical Institute of Medical Genetics, Department of Obstetrics and Gynecology, University Medical Centre Ljubljana, Ljubljana, Slovenia

38 The Scripps Translational Science Institute, The Scripps Research Institute, La Jolla, CA, USA

39 Department of Molecular Medicine and Surgery, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden

40 Centre for Inherited Metabolic Disorders, Karolinska University Hospital, Stockholm, Sweden

41 Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden

42 Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden

43 School of Biotechnology, Science for Life Laboratory, Royal Institute of Technology, Stockholm, Sweden

44 Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden

45 Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden

46 Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

47 Sanofi, Cambridge, MA, USA

48 Seven Bridges Genomics Inc, Cambridge, MA, USA

49 River Road Bio, Potomac, MD, USA

50 Computational and Mathematical Biology Genome Institute of Singapore, A*STAR, Singapore, Singapore

51 Strand Life Sciences, Bangalore, India

52 Tel Aviv University, Tel Aviv, Israel

53 Institute for Systems Biology, Seattle, WA, USA

54 Ingenuity Systems, Redwood City, California, USA

55 University of Texas Graduate School of Biomedical Sciences, Department of Epidemiology, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

56 Division of Next Generation Sequencing, Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, UTHealth, Houston, TX, USA

57 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

58 Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA

59 Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Palo Alto, CA, USA

60 National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA

61 Instituto de Biomedicina y Biotecnología de Cantabria-IBBTEC, Santander, Cantabria, Spain

62 Consejo Superior de Investigaciones Científicasl (CSIC), Santander, Cantabria, Spain

63 Universidad de Cantabria, Santander, Cantabria, Spain

64 SODERCAN, Santander, Cantabria, Spain

65 Departamento de Biología Molecular, Universidad de Cantabria, Santander, Cantabria, Spain

66 División de Pediatría. Departamento de Ciencias Médicas y Quirúrgicas, Universidad de Cantabria Santander, Cantabria, Spain

67 Hospital Universitario Marqués de Valdecilla -IFIMAV (Instituto de Formación e Investigación Marqués de Valdecilla), Santander, Cantabria, Spain

68 CIBER Epidemiología y Salud Pública (CIBERESP), Santander, Cantabria, Spain

69 Instituto de Formación e Investigación Marqués de Valdecilla (IFIMAV), Santander, Cantabria, Spain

70 Omicia, Inc, Emeryville, CA, USA

71 Real Time Genomics, Inc, San Bruno, CA, USA

72 InVitae (formerly Locus Development), 458 Brannan Street, San Francisco, CA 94107, USA

73 Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, New York, NY, USA

74 Utah Foundation for Biomedical Research, Salt Lake City, UT, USA

75 Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah, USA

76 Division of Cardiology and Department of Biomedical Informatics, University of Utah School of Medicine, Salt Lake City, Utah, USA

77 Department of Human Genetics, Eccles Institute of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah, USA

78 Biomedical Informatics, University of Utah School of Medicine, Salt Lake City, Utah, USA

79 Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA

80 Program of Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA

81 Biostatistics Resource, Keck Laboratory, Yale University, New Haven, CT, USA

82 Departments of Neurosurgery and Neurobiology, Yale University School of Medicine, New Haven, CT, USA

83 Department of Genetics, Yale University School of Medicine, New Haven, CT, USA

84 Department of Molecular Biophysics and Biochemistry, WM Keck Foundation Biotechnology Resource Laboratory, Yale University, New Haven, CT, USA

85 Pearlgen, Inc, Durham, NC, USA

86 Novocraft Technologies Sdn Bhd, Selangor, Malaysia

87 Children’s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada

88 Alberta Children’s Hospital Research Institute (ACHRI), University of Calgary, Calgary, AB, Canada

89 Department of Medical Genetics and Alberta Children’s Hospital Research Institute (ACHRI), University of Calgary, Calgary, AB, Canada

90 Centre of Genomics and Policy, McGill University, Montreal, QC, Canada

91 McGill University and Genome Quebec Innovation Centre, Montreal, QC, Canada

92 McLaughlin Centre, University of Toronto, The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada

93 Department of Medicine, Centre de Recherche du CHU Ste-Justine, University of Montreal, Montreal, QC, Canada

94 Current Address: Zoological Department, Naturhistorisches Museum, Vienna, Austria

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Genome Biology 2014, 15:R53  doi:10.1186/gb-2014-15-3-r53

Published: 25 March 2014

Additional files

Additional file 1:

The complete entry from the Brigham and Woman’s Team containing seven PDF files, six PNG image files, and one XLS table.

Format: ZIP Size: 3.6MB Download file

Open Data

Additional file 2:

The entry from the Genomatix/CeGaT/University Hospital of Bonn team containing five PDF files and six XLS tables.

Format: ZIP Size: 1.6MB Download file

Open Data

Additional file 3:

The entry from the University of Iowa.

Format: PDF Size: 2.4MB Download file

This file can be viewed with: Adobe Acrobat Reader

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Additional file 4:

Individual and aggregated results from questions in the structured surveys of contestants’ practices. Responses are broken down into separate sheets according to category as follows: PART A: Consenting and explanatory materials for whole exome/genome sequencing technology. PART B: About your summary clinical report. PART C: Interpretive reports. PART D: Revisible reporting. PART E: Variant identification. PART F: Data analysis. PART G: Validation of analytical tools. PART H: Methods predicting variant pathogenicity. PART I: From variants to phenotype. PART J: Overall impressions and team composition. PART K: Follow-up questions, costs and sensitivity.

Format: XLSX Size: 135KB Download file

Open Data