Abstract
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 was 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.
Original language | English |
---|---|
Journal | Genome biology |
Volume | 15 |
Issue number | 3 |
DOIs | |
Publication status | Published - 25 Mar 2014 |
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Brownstein, C. A., Beggs, A. H., Homer, N., Merriman, B., Yu, T. W., Flannery, K. C., Dechene, E. T., Towne, M. C., Savage, S. K., Price, E. N., Holm, I. A., Luquette, L. J., Lyon, E., Majzoub, J., Neupert, P., McCallie, D., Szolovits, P., Willard, H. F., Mendelsohn, N. J., ... Margulies, D. M. (2014). 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, 15(3). https://doi.org/10.1186/gb-2014-15-3-r53
Brownstein, Catherine A ; Beggs, Alan H ; Homer, Nils et al. / An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge. In: Genome biology. 2014 ; Vol. 15, No. 3.
@article{18a6047071bb4491bd151b087a80c700,
title = "An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge.",
abstract = "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 was 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.",
author = "Brownstein, {Catherine A} and Beggs, {Alan H} and Nils Homer and Barry Merriman and Yu, {Timothy W} and Flannery, {Katherine C} and Dechene, {Elizabeth T} and Towne, {Meghan C} and Savage, {Sarah K} and Price, {Emily N} and Holm, {Ingrid A} and Luquette, {Lovelace J} and Elaine Lyon and Joseph Majzoub and Peter Neupert and David McCallie and Peter Szolovits and Willard, {Huntington F} and Mendelsohn, {Nancy J} and Renee Temme and Finkel, {Richard S} and Yum, {Sabrina W} and Livija Medne and Sunyaev, {Shamil R} and Ivan Adzhubey and Cassa, {Christopher A} and {de Bakker}, {Paul Iw} and Hatice Duzkale and {Dworzy Ski}, Piotr and William Fairbrother and Laurent Francioli and Funke, {Birgit H} and Giovanni, {Monica A} and Handsaker, {Robert E} and Kasper Lage and Lebo, {Matthew S} and Monkol Lek and Ignaty Leshchiner and Macarthur, {Daniel G} and McLaughlin, {Heather M} and Murray, {Michael F} and Pers, {Tune H} and Polak, {Paz P} and Soumya Raychaudhuri and Rehm, {Heidi L} and Rachel Soemedi and Stitziel, {Nathan O} and Sara Vestecka and Jochen Supper and Claudia Gugenmus and Bernward Klocke and Alexander Hahn and Max Schubach and Mortiz Menzel and Saskia Biskup and Peter Freisinger and Mario Deng and Martin Braun and Sven Perner and Smith, {Richard Jh} and Andorf, {Janeen L} and Jian Huang and Kelli Ryckman and Sheffield, {Val C} and Stone, {Edwin M} and Thomas Bair and Black-Ziegelbein, {E Ann} and Braun, {Terry A} and Benjamin Darbro and Deluca, {Adam P} and Kolbe, {Diana L} and Scheetz, {Todd E} and Shearer, {Aiden E} and Rama Sompallae and Kai Wang and Bassuk, {Alexander G} and Erik Edens and Katherine Mathews and Moore, {Steven A} and Shchelochkov, {Oleg A} and Pamela Trapane and Aaron Bossler and Campbell, {Colleen A} and Heusel, {Jonathan W} and Anne Kwitek and Tara Maga and Karin Panzer and Thomas Wassink and {Van Daele}, Douglas and Hela Azaiez and Kevin Booth and Nic Meyer and Segal, {Michael M} and Williams, {Marc S} and Gerard Tromp and Peter White and Donald Corsmeier and Sara Fitzgerald-Butt and Gail Herman and Devon Lamb-Thrush and McBride, {Kim L} and David Newsom and Pierson, {Christopher R} and Rakowsky, {Alexander T} and Ale Maver and {Lovre I}, Luca and {Palanda I}, Anja and Borut Peterlin and Ali Torkamani and Anna Wedell and Mikael Huss and Andrey Alexeyenko and Lindvall, {Jessica M} and M{\aa}ns Magnusson and Daniel Nilsson and Henrik Stranneheim and Fulya Taylan and Christian Gilissen and Alexander Hoischen and {van Bon}, Bregje and Helger Yntema and Marcel Nelen and Weidong Zhang and Jason Sager and Lu Zhang and Kathryn Blair and Deniz Kural and Michael Cariaso and Lennon, {Greg G} and Asif Javed and Saloni Agrawal and Ng, {Pauline C} and Sandhu, {Komal S} and Shuba Krishna and Vamsi Veeramachaneni and Ofer Isakov and Eran Halperin and Eitan Friedman and Noam Shomron and Gustavo Glusman and Roach, {Jared C} and Juan Caballero and Cox, {Hannah C} and Denise Mauldin and Ament, {Seth A} and Lee Rowen and Richards, {Daniel R} and Lucas, {F Anthony} and Gonzalez-Garay, {Manuel L} and Caskey, {C Thomas} and Yu Bai and Ying Huang and Fang Fang and Yan Zhang and Zhengyuan Wang and Jorge Barrera and Garcia-Lobo, {Juan M} and Domingo Gonz{\'a}lez-Lamu{\~n}o and Javier Llorca and Rodriguez, {Maria C} and Ignacio Varela and Reese, {Martin G} and {De La Vega}, {Francisco M} and Edward Kiruluta and Michele Cargill and Hart, {Reece K} and Sorenson, {Jon M} and Lyon, {Gholson J} and Stevenson, {David A} and Bray, {Bruce E} and Moore, {Barry M} and Karen Eilbeck and Mark Yandell and Hongyu Zhao and Lin Hou and Xiaowei Chen and Xiting Yan and Mengjie Chen and Cong Li and Can Yang and Murat Gunel and Peining Li and Yong Kong and Alexander, {Austin C} and Albertyn, {Zayed I} and Boycott, {Kym M} and Bulman, {Dennis E} and Gordon, {Paul Mk} and Innes, {A Micheil} and Knoppers, {Bartha M} and Jacek Majewski and Marshall, {Christian R} and Parboosingh, {Jillian S} and Sawyer, {Sarah L} and Samuels, {Mark E} and Jeremy Schwartzentruber and Kohane, {Isaac S} and Margulies, {David M}",
note = "R01 HL109758, NHLBI NIH HHS, United States",
year = "2014",
month = mar,
day = "25",
doi = "10.1186/gb-2014-15-3-r53",
language = "English",
volume = "15",
journal = "Genome biology",
issn = "1465-6914",
publisher = "Springer Nature",
number = "3",
}
Brownstein, CA, Beggs, AH, Homer, N, Merriman, B, Yu, TW, Flannery, KC, Dechene, ET, Towne, MC, Savage, SK, Price, EN, Holm, IA, Luquette, LJ, Lyon, E, Majzoub, J, Neupert, P, McCallie, D, Szolovits, P, Willard, HF, Mendelsohn, NJ, Temme, R, Finkel, RS, Yum, SW, Medne, L, Sunyaev, SR, Adzhubey, I, Cassa, CA, de Bakker, PI, Duzkale, H, Dworzy Ski, P, Fairbrother, W, Francioli, L, Funke, BH, Giovanni, MA, Handsaker, RE, Lage, K, Lebo, MS, Lek, M, Leshchiner, I, Macarthur, DG, McLaughlin, HM, Murray, MF, Pers, TH, Polak, PP, Raychaudhuri, S, Rehm, HL, Soemedi, R, Stitziel, NO, Vestecka, S, Supper, J, Gugenmus, C, Klocke, B, Hahn, A, Schubach, M, Menzel, M, Biskup, S, Freisinger, P, Deng, M, Braun, M, Perner, S, Smith, RJ, Andorf, JL, Huang, J, Ryckman, K, Sheffield, VC, Stone, EM, Bair, T, Black-Ziegelbein, EA, Braun, TA, Darbro, B, Deluca, AP, Kolbe, DL, Scheetz, TE, Shearer, AE, Sompallae, R, Wang, K, Bassuk, AG, Edens, E, Mathews, K, Moore, SA, Shchelochkov, OA, Trapane, P, Bossler, A, Campbell, CA, Heusel, JW, Kwitek, A, Maga, T, Panzer, K, Wassink, T, Van Daele, D, Azaiez, H, Booth, K, Meyer, N, Segal, MM, Williams, MS, Tromp, G, White, P, Corsmeier, D, Fitzgerald-Butt, S, Herman, G, Lamb-Thrush, D, McBride, KL, Newsom, D, Pierson, CR, Rakowsky, AT, Maver, A, Lovre I, L, Palanda I, A, Peterlin, B, Torkamani, A, Wedell, A, Huss, M, Alexeyenko, A, Lindvall, JM, Magnusson, M, Nilsson, D, Stranneheim, H, Taylan, F, Gilissen, C, Hoischen, A, van Bon, B, Yntema, H, Nelen, M, Zhang, W, Sager, J, Zhang, L, Blair, K, Kural, D, Cariaso, M, Lennon, GG, Javed, A, Agrawal, S, Ng, PC, Sandhu, KS, Krishna, S, Veeramachaneni, V, Isakov, O, Halperin, E, Friedman, E, Shomron, N, Glusman, G, Roach, JC, Caballero, J, Cox, HC, Mauldin, D, Ament, SA, Rowen, L, Richards, DR, Lucas, FA, Gonzalez-Garay, ML, Caskey, CT, Bai, Y, Huang, Y, Fang, F, Zhang, Y, Wang, Z, Barrera, J, Garcia-Lobo, JM, González-Lamuño, D, Llorca, J, Rodriguez, MC, Varela, I, Reese, MG, De La Vega, FM, Kiruluta, E, Cargill, M, Hart, RK, Sorenson, JM, Lyon, GJ, Stevenson, DA, Bray, BE, Moore, BM, Eilbeck, K, Yandell, M, Zhao, H, Hou, L, Chen, X, Yan, X, Chen, M, Li, C, Yang, C, Gunel, M, Li, P, Kong, Y, Alexander, AC, Albertyn, ZI, Boycott, KM, Bulman, DE, Gordon, PM, Innes, AM, Knoppers, BM, Majewski, J, Marshall, CR, Parboosingh, JS, Sawyer, SL, Samuels, ME, Schwartzentruber, J, Kohane, IS & Margulies, DM 2014, '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, vol. 15, no. 3. https://doi.org/10.1186/gb-2014-15-3-r53
An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge. / Brownstein, Catherine A; Beggs, Alan H; Homer, Nils et al.
In: Genome biology, Vol. 15, No. 3, 25.03.2014.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge.
AU - Brownstein, Catherine A
AU - Beggs, Alan H
AU - Homer, Nils
AU - Merriman, Barry
AU - Yu, Timothy W
AU - Flannery, Katherine C
AU - Dechene, Elizabeth T
AU - Towne, Meghan C
AU - Savage, Sarah K
AU - Price, Emily N
AU - Holm, Ingrid A
AU - Luquette, Lovelace J
AU - Lyon, Elaine
AU - Majzoub, Joseph
AU - Neupert, Peter
AU - McCallie, David
AU - Szolovits, Peter
AU - Willard, Huntington F
AU - Mendelsohn, Nancy J
AU - Temme, Renee
AU - Finkel, Richard S
AU - Yum, Sabrina W
AU - Medne, Livija
AU - Sunyaev, Shamil R
AU - Adzhubey, Ivan
AU - Cassa, Christopher A
AU - de Bakker, Paul Iw
AU - Duzkale, Hatice
AU - Dworzy Ski, Piotr
AU - Fairbrother, William
AU - Francioli, Laurent
AU - Funke, Birgit H
AU - Giovanni, Monica A
AU - Handsaker, Robert E
AU - Lage, Kasper
AU - Lebo, Matthew S
AU - Lek, Monkol
AU - Leshchiner, Ignaty
AU - Macarthur, Daniel G
AU - McLaughlin, Heather M
AU - Murray, Michael F
AU - Pers, Tune H
AU - Polak, Paz P
AU - Raychaudhuri, Soumya
AU - Rehm, Heidi L
AU - Soemedi, Rachel
AU - Stitziel, Nathan O
AU - Vestecka, Sara
AU - Supper, Jochen
AU - Gugenmus, Claudia
AU - Klocke, Bernward
AU - Hahn, Alexander
AU - Schubach, Max
AU - Menzel, Mortiz
AU - Biskup, Saskia
AU - Freisinger, Peter
AU - Deng, Mario
AU - Braun, Martin
AU - Perner, Sven
AU - Smith, Richard Jh
AU - Andorf, Janeen L
AU - Huang, Jian
AU - Ryckman, Kelli
AU - Sheffield, Val C
AU - Stone, Edwin M
AU - Bair, Thomas
AU - Black-Ziegelbein, E Ann
AU - Braun, Terry A
AU - Darbro, Benjamin
AU - Deluca, Adam P
AU - Kolbe, Diana L
AU - Scheetz, Todd E
AU - Shearer, Aiden E
AU - Sompallae, Rama
AU - Wang, Kai
AU - Bassuk, Alexander G
AU - Edens, Erik
AU - Mathews, Katherine
AU - Moore, Steven A
AU - Shchelochkov, Oleg A
AU - Trapane, Pamela
AU - Bossler, Aaron
AU - Campbell, Colleen A
AU - Heusel, Jonathan W
AU - Kwitek, Anne
AU - Maga, Tara
AU - Panzer, Karin
AU - Wassink, Thomas
AU - Van Daele, Douglas
AU - Azaiez, Hela
AU - Booth, Kevin
AU - Meyer, Nic
AU - Segal, Michael M
AU - Williams, Marc S
AU - Tromp, Gerard
AU - White, Peter
AU - Corsmeier, Donald
AU - Fitzgerald-Butt, Sara
AU - Herman, Gail
AU - Lamb-Thrush, Devon
AU - McBride, Kim L
AU - Newsom, David
AU - Pierson, Christopher R
AU - Rakowsky, Alexander T
AU - Maver, Ale
AU - Lovre I, Luca
AU - Palanda I, Anja
AU - Peterlin, Borut
AU - Torkamani, Ali
AU - Wedell, Anna
AU - Huss, Mikael
AU - Alexeyenko, Andrey
AU - Lindvall, Jessica M
AU - Magnusson, Måns
AU - Nilsson, Daniel
AU - Stranneheim, Henrik
AU - Taylan, Fulya
AU - Gilissen, Christian
AU - Hoischen, Alexander
AU - van Bon, Bregje
AU - Yntema, Helger
AU - Nelen, Marcel
AU - Zhang, Weidong
AU - Sager, Jason
AU - Zhang, Lu
AU - Blair, Kathryn
AU - Kural, Deniz
AU - Cariaso, Michael
AU - Lennon, Greg G
AU - Javed, Asif
AU - Agrawal, Saloni
AU - Ng, Pauline C
AU - Sandhu, Komal S
AU - Krishna, Shuba
AU - Veeramachaneni, Vamsi
AU - Isakov, Ofer
AU - Halperin, Eran
AU - Friedman, Eitan
AU - Shomron, Noam
AU - Glusman, Gustavo
AU - Roach, Jared C
AU - Caballero, Juan
AU - Cox, Hannah C
AU - Mauldin, Denise
AU - Ament, Seth A
AU - Rowen, Lee
AU - Richards, Daniel R
AU - Lucas, F Anthony
AU - Gonzalez-Garay, Manuel L
AU - Caskey, C Thomas
AU - Bai, Yu
AU - Huang, Ying
AU - Fang, Fang
AU - Zhang, Yan
AU - Wang, Zhengyuan
AU - Barrera, Jorge
AU - Garcia-Lobo, Juan M
AU - González-Lamuño, Domingo
AU - Llorca, Javier
AU - Rodriguez, Maria C
AU - Varela, Ignacio
AU - Reese, Martin G
AU - De La Vega, Francisco M
AU - Kiruluta, Edward
AU - Cargill, Michele
AU - Hart, Reece K
AU - Sorenson, Jon M
AU - Lyon, Gholson J
AU - Stevenson, David A
AU - Bray, Bruce E
AU - Moore, Barry M
AU - Eilbeck, Karen
AU - Yandell, Mark
AU - Zhao, Hongyu
AU - Hou, Lin
AU - Chen, Xiaowei
AU - Yan, Xiting
AU - Chen, Mengjie
AU - Li, Cong
AU - Yang, Can
AU - Gunel, Murat
AU - Li, Peining
AU - Kong, Yong
AU - Alexander, Austin C
AU - Albertyn, Zayed I
AU - Boycott, Kym M
AU - Bulman, Dennis E
AU - Gordon, Paul Mk
AU - Innes, A Micheil
AU - Knoppers, Bartha M
AU - Majewski, Jacek
AU - Marshall, Christian R
AU - Parboosingh, Jillian S
AU - Sawyer, Sarah L
AU - Samuels, Mark E
AU - Schwartzentruber, Jeremy
AU - Kohane, Isaac S
AU - Margulies, David M
N1 - R01 HL109758, NHLBI NIH HHS, United States
PY - 2014/3/25
Y1 - 2014/3/25
N2 - 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 was 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.
AB - 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 was 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.
U2 - 10.1186/gb-2014-15-3-r53
DO - 10.1186/gb-2014-15-3-r53
M3 - Article
C2 - 24667040
SN - 1465-6914
VL - 15
JO - Genome biology
JF - Genome biology
IS - 3
ER -
Brownstein CA, Beggs AH, Homer N, Merriman B, Yu TW, Flannery KC et al. 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. 2014 Mar 25;15(3). doi: 10.1186/gb-2014-15-3-r53