Article open access publication

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

Genome Biology, Springer Nature, ISSN 1465-6906

Volume 15, 3, 2014

DOI:10.1186/gb-2014-15-3-r53, Dimensions: pub.1000435282, PMC: PMC4073084, PMID: 24667040,


Supper, Jochen (21) (22)
Freisinger, Peter (22) (23)
Wang, Kai (25)
Maga, Tara (25)
Meyer, Nic (25)
Palandačić, Anja (29) (30)
Wedell, Anna (32) (33)
Magnusson, Måns (32) (33)
Nilsson, Daniel (32) (33)
Zhang, Lu (38)
Rowen, Lee (43)
Bai, Yu (48)
Fang, Fang (49)
Zhang, Yan (50)
Barrera, Jorge (51) (52) (53) (54)
Garcia-Lobo, Juan M (51) (52) (53) (54)
Llorca, Javier (51) (56) (57)
Rodriguez, Maria C (51) (52) (53) (54)
Varela, Ignacio (51) (52) (53) (54)
Lyon, Gholson J (61) (62)
Hou, Lin (63)
Li, Cong (63)
Yang, Can (63)
Kong, Yong (63)

* Corresponding author



  1. (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. (2) Claritas Genomics (United States), grid.465147.5
  3. (3) Thermo Fisher Scientific (United States), grid.418190.5
  4. (4) Harvard University, grid.38142.3c
  5. (5) University of Utah, grid.223827.e
  6. (6) Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
  7. (7) Microsoft (United States), grid.419815.0
  8. (8) Cerner (United States), grid.418415.d
  9. (9) Massachusetts Institute of Technology, grid.116068.8
  10. (10) Duke University, grid.26009.3d
  11. (11) Children's Hospitals and Clinics of Minnesota, grid.418506.e
  12. (12) Nemours Children's Clinic, grid.428618.1
  13. (13) Division of Neurology, Children’s Hospital of Philadelphia, and Department of Neurology, Perelmen School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
  14. (14) Children's Hospital of Philadelphia, grid.239552.a
  15. (15) University Medical Center Utrecht, grid.7692.a
  16. (16) Technical University of Denmark, grid.5170.3, DTU
  17. (17) Brown University, grid.40263.33
  18. (18) Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
  19. (19) Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
  20. (20) Boston Children's Hospital, grid.2515.3
  21. (21) Genomatix Software GmbH, Bayerstr 85a, Munich, Germany
  22. (22) CeGaT (Germany), grid.498061.2
  23. (23) University Children's Hospital Tübingen, grid.488549.c
  24. (24) Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Bonn, Germany
  25. (25) University of Iowa, grid.214572.7
  26. (26) SimulConsult, grid.437840.c
  27. (27) Geisinger Health System, grid.280776.c
  28. (28) Nationwide Children’s Hospital, Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA
  29. (29) Ljubljana University Medical Centre, grid.29524.38
  30. (30) Natural History Museum Vienna, grid.425585.b
  31. (31) Scripps Research Institute, grid.214007.0
  32. (32) Karolinska Institute, grid.4714.6
  33. (33) Karolinska University Hospital, grid.24381.3c
  34. (34) Stockholm University, grid.10548.38
  35. (35) Royal Institute of Technology, grid.5037.1
  36. (36) Radboud University Nijmegen Medical Centre, grid.10417.33
  37. (37) Sanofi (United States), grid.417555.7
  38. (38) Seven Bridges Genomics (United States), grid.492568.4
  39. (39) River Road Bio, Potomac, MD, USA
  40. (40) Agency for Science, Technology and Research, grid.185448.4
  41. (41) Strand Life Sciences (India), grid.465051.3
  42. (42) Tel Aviv University, grid.12136.37
  43. (43) Institute for Systems Biology, grid.64212.33
  44. (44) Ingenuity Systems, Redwood City, California, USA
  45. (45) The University of Texas MD Anderson Cancer Center, grid.240145.6
  46. (46) The University of Texas Health Science Center at Houston, grid.267308.8
  47. (47) Baylor College of Medicine, grid.39382.33
  48. (48) Regeneron (United States), grid.418961.3
  49. (49) Lucile Packard Children's Hospital, grid.414123.1
  50. (50) National Heart Lung and Blood Institute, grid.279885.9
  51. (51) University of Cantabria, grid.7821.c
  52. (52) Consejo Superior de Investigaciones Científicasl (CSIC), Santander, Cantabria, Spain
  53. (53) Institute of Biomedicine and Biotechnology of Cantabria, grid.507090.b
  54. (54) Sodercan, grid.474195.a
  55. (55) Hospital Universitario Marqués de Valdecilla, IFIMAV (Instituto de Formación e Investigación Marqués de Valdecilla), Santander, Cantabria, Spain
  56. (56) Institute of Health Carlos III, grid.413448.e
  57. (57) Instituto de Formación e Investigación Marqués de Valdecilla (IFIMAV), Santander, Cantabria, Spain
  58. (58) Omicia (United States), grid.423110.5
  59. (59) Real Time Genomics, Inc, San Bruno, CA, USA
  60. (60) Invitae (United States), grid.465210.4
  61. (61) Cold Spring Harbor Laboratory, grid.225279.9
  62. (62) Utah Foundation for Biomedical Research, Salt Lake City, UT, USA
  63. (63) Yale University, grid.47100.32
  64. (64) Pearlgen, Inc, Durham, NC, USA
  65. (65) Novocraft Technologies Sdn Bhd, Selangor, Malaysia
  66. (66) Children’s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada
  67. (67) University of Calgary, grid.22072.35
  68. (68) McGill University, grid.14709.3b
  69. (69) McGill University and Génome Québec Innovation Centre, grid.411640.6
  70. (70) University of Toronto, grid.17063.33
  71. (71) Department of Medicine, Centre de Recherche du CHU Ste-Justine, University of Montreal, Montreal, QC, Canada


BACKGROUND: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.


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Times Cited: 79

Field Citation Ratio (FCR): 9

Relative Citation ratio (RCR): 2.55

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