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Grant Details

Grant Number: 5U41HG007346-03 Interpret this number
Primary Investigator: Brenner, Steven
Organization: University Of California Berkeley
Project Title: Center for Critical Assessment of Genome Interpretation
Fiscal Year: 2017
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Abstract

? DESCRIPTION (provided by applicant): New genomic data hold the promise of revolutionizing our understanding and treatment of human disease, and hence of greatly influencing clinical practice. Multiple barriers stand between the acquisition of the data and realizing these and other benefits. In particular, powerful and well-characterized computational methods for deducing the disease relevant phenotypic impact of genomic variants are needed. Over fifty such methods already exist, but currently, even though some are already deployed in clinical practice, we do not know how well these perform on relevant genome interpretation tasks. Further, it is already clear that new and more sophisticated approaches must be developed to fully meet the new challenges. The Center for Critical Assessment of Genome Interpretation (C-CAGI) will address these needs, through ongoing objective evaluation of the state of the art in relating genetic information to phenotype, particularly the relationship between human genetic variation and health. These goals are embraced by three specific aims: 1. Assess the quality of current computational methods for interpreting genomic variation data, and highlight innovations & progress. Building on successful initial experiments in 2010, 2011 and 2013, C-CAGI will conduct community-wide experiments in which participants make bona fide blinded predictions of disease related phenotypes on the basis of genomic data. These are evaluated by independent assessors with access to the correct answers, to determine how well methods work both relatively and absolutely. These assessments will establish the state-of-the art and advance the field. 2. Guide future research efforts in computational genome interpretation and build a strong community for collaboration and interaction. C-CAGI aims to engage and expand the community of researchers interpreting the phenotypic impact of genomic variation with CAGI workshops, hackathons, tutorials, and other mechanisms. We hope to use CAGI to spur and recognize innovative approaches to the breadth of practical and clinical research. The C-CAGI will also encourage and commission experimental studies necessary for focused testing of the computational methods. C-CAGI operates on a robust ethical foundation in using human research participant data, supported by the CAGI Ethics Forum. 3. Broadly disseminate the results and conclusions from the CAGI experiments and analysis. C-CAGI aims to be the central resource for information on interpretation of genomic variation. This dissemination to the broader scientific and clinical community will be using its publications, best practice guides, and web resources, and through presentations, tutorials, and workshops at international meetings.

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Publications

Registered access: authorizing data access.
Authors: Dyke S.O.M. , Linden M. , Lappalainen I. , De Argila J.R. , Carey K. , Lloyd D. , Spalding J.D. , Cabili M.N. , Kerry G. , Foreman J. , et al. .
Source: European Journal Of Human Genetics : Ejhg, 2018 Dec; 26(12), p. 1721-1731.
EPub date: 2018-08-02 00:00:00.0.
PMID: 30069064
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PRECISION MEDICINE: FROM DIPLOTYPES TO DISPARITIES TOWARDS IMPROVED HEALTH AND THERAPIES.
Authors: Crawford D.C. , Morgan A.A. , Denny J.C. , Aronow B.J. , Brenner S.E. .
Source: Pacific Symposium On Biocomputing. Pacific Symposium On Biocomputing, 2018; 23, p. 389-399.
PMID: 29218899
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Methods and tools for assessing the impact of genetic variations: The 2017 Annual Scientific Meeting of the Human Genome Variation Society.
Authors: Oetting W.S. , Béroud C. , Brenner S.E. , Greenblatt M.S. , Karchin R. , Mooney S.D. .
Source: Human Mutation, 2017-12-28 00:00:00.0; , .
EPub date: 2017-12-28 00:00:00.0.
PMID: 29282786
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Stratified polygenic risk prediction model with application to CAGI bipolar disorder sequencing data.
Authors: Wang M.H. , Chang B. , Sun R. , Hu I. , Xia X. , Wu W.K.K. , Chong K.C. , Zee B.C. .
Source: Human Mutation, 2017 Sep; 38(9), p. 1235-1239.
EPub date: 2017-06-13 00:00:00.0.
PMID: 28419606
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Reports from CAGI: The Critical Assessment of Genome Interpretation.
Authors: Hoskins R.A. , Repo S. , Barsky D. , Andreoletti G. , Moult J. , Brenner S.E. .
Source: Human Mutation, 2017 Sep; 38(9), p. 1039-1041.
PMID: 28817245
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Assessing predictions of fitness effects of missense mutations in SUMO-conjugating enzyme UBE2I.
Authors: Zhang J. , Kinch L.N. , Cong Q. , Weile J. , Sun S. , Cote A.G. , Roth F.P. , Grishin N.V. .
Source: Human Mutation, 2017 Sep; 38(9), p. 1051-1063.
PMID: 28817247
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Working toward precision medicine: Predicting phenotypes from exomes in the Critical Assessment of Genome Interpretation (CAGI) challenges.
Authors: Daneshjou R. , Wang Y. , Bromberg Y. , Bovo S. , Martelli P.L. , Babbi G. , Lena P.D. , Casadio R. , Edwards M. , Gifford D. , et al. .
Source: Human Mutation, 2017-06-21 00:00:00.0; , .
EPub date: 2017-06-21 00:00:00.0.
PMID: 28634997
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Deep bipolar: Identifying genomic mutations for bipolar disorder via deep learning.
Authors: Laksshman S. , Bhat R.R. , Viswanath V. , Li X. .
Source: Human Mutation, 2017-06-10 00:00:00.0; , .
EPub date: 2017-06-10 00:00:00.0.
PMID: 28600868
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Ensemble variant interpretation methods to predict enzyme activity and assign pathogenicity in the CAGI4 NAGLU (Human N-acetyl-glucosaminidase) and UBE2I (Human SUMO-ligase) challenges.
Authors: Yin Y. , Kundu K. , Pal L.R. , Moult J. .
Source: Human Mutation, 2017-05-24 00:00:00.0; , .
EPub date: 2017-05-24 00:00:00.0.
PMID: 28544272
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Objective assessment of the evolutionary action equation for the fitness effect of missense mutations across CAGI-blinded contests.
Authors: Katsonis P. , Lichtarge O. .
Source: Human Mutation, 2017-05-23 00:00:00.0; , .
EPub date: 2017-05-23 00:00:00.0.
PMID: 28544059
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Matching phenotypes to whole genomes: Lessons learned from four iterations of the personal genome project community challenges.
Authors: Cai B. , Li B. , Kiga N. , Thusberg J. , Bergquist T. , Chen Y.C. , Niknafs N. , Carter H. , Tokheim C. , Beleva-Guthrie V. , et al. .
Source: Human Mutation, 2017-05-23 00:00:00.0; , .
EPub date: 2017-05-23 00:00:00.0.
PMID: 28544481
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Missense variant pathogenicity predictors generalize well across a range of function-specific prediction challenges.
Authors: Pejaver V. , Mooney S.D. , Radivojac P. .
Source: Human Mutation, 2017-05-16 00:00:00.0; , .
EPub date: 2017-05-16 00:00:00.0.
PMID: 28508593
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Performance of in silico tools for the evaluation of p16INK4a (CDKN2A) variants in CAGI.
Authors: Carraro M. , Minervini G. , Giollo M. , Bromberg Y. , Capriotti E. , Casadio R. , Dunbrack R. , Elefanti L. , Fariselli P. , Ferrari C. , et al. .
Source: Human Mutation, 2017-04-25 00:00:00.0; , .
EPub date: 2017-04-25 00:00:00.0.
PMID: 28440912
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Lessons from the CAGI-4 Hopkins clinical panel challenge.
Authors: Chandonia J.M. , Adhikari A. , Carraro M. , Chhibber A. , Cutting G.R. , Fu Y. , Gasparini A. , Jones D.T. , Kramer A. , Kundu K. , et al. .
Source: Human Mutation, 2017-04-11 00:00:00.0; , .
EPub date: 2017-04-11 00:00:00.0.
PMID: 28397312
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Non-Coding Variation: The 2016 Annual Scientific Meeting of the Human Genome Variation Society.
Authors: Oetting W.S. , Béroud C. , Brenner S.E. , Greenblatt M. , Karchin R. , Mooney S.D. , Sunyaev S. .
Source: Human Mutation, 2017 Apr; 38(4), p. 460-463.
EPub date: 2017-02-14 00:00:00.0.
PMID: 28054414
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Benchmarking Predictions Of Allostery In Liver Pyruvate Kinase In Cagi4
Authors: Xu Q. , Tang Q. , Katsonis P. , Lichtarge O. , Jones D. , Bovo S. , Babbi G. , Martelli P.L. , Casadio R. , Lee G.R. , et al. .
Source: Human Mutation, 2017-03-29 00:00:00.0; , .
PMID: 28370845
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Pon-p And Pon-p2 Predictor Performance In Cagi Challenges: Lessons Learned
Authors: Niroula A. , Vihinen M. .
Source: Human Mutation, 2017-02-22 00:00:00.0; , .
PMID: 28224672
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Predicting Gene Expression In Massively Parallel Reporter Assays: A Comparative Study
Authors: Kreimer A. , Zeng H. , Edwards M.D. , Guo Y. , Tian K. , Shin S. , Welch R. , Wainberg M. , Mohan R. , Sinnott-Armstrong N.A. , et al. .
Source: Human Mutation, 2017-02-21 00:00:00.0; , .
PMID: 28220625
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Accurate Eqtl Prioritization With An Ensemble-based Framework
Authors: Zeng H. , Edwards M.D. , Guo Y. , Gifford D.K. .
Source: Human Mutation, 2017-02-21 00:00:00.0; , .
PMID: 28224684
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Predicting Enhancer Activity And Variant Impact Using Gkm-svm
Authors: Beer M.A. .
Source: Human Mutation, 2017-01-25 00:00:00.0; , .
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Blind prediction of deleterious amino acid variations with SNPs&GO.
Authors: Capriotti E. , Martelli P.L. , Fariselli P. , Casadio R. .
Source: Human Mutation, 2017-01-19 00:00:00.0; , .
EPub date: 2017-01-19 00:00:00.0.
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Crohn Disease Risk Prediction-best Practices And Pitfalls With Exome Data
Authors: Giollo M. , Jones D.T. , Carraro M. , Leonardi E. , Ferrari C. , Tosatto S.C. .
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Pathogenicity Interpretation in the Age of Precision Medicine: The 2015 Annual Scientific Meeting of the Human Genome Variation Society.
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Precision Medicine: Data And Discovery For Improved Health And Therapy
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pathogenic variant in a family with paroxysmal kinesigenic dyskinesia and benign familial infantile seizures.
Authors: Lu J.G. , Bishop J. , Cheyette S. , Zhulin I.B. , Guo S. , Sobreira N. , Brenner S.E. .
Source: Cold Spring Harbor Molecular Case Studies, 2018 02; 4(1), .
EPub date: 2018-02-01 00:00:00.0.
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