Prediction of the functional impact of missense variants in BRCA1 and BRCA2 with BRCA-ML

被引：18

作者：

Hart, Steven N. ^{[1
]}

Polley, Eric C. ^{[1
]}

Shimelis, Hermella ^{[2
]}

Yadav, Siddhartha ^{[3
]}

Couch, Fergus J. ^{[1
,2
]}

机构：

[1] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA

[2] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA

[3] Mayo Clin, Dept Oncol, Rochester, MN USA

来源：

NPJ BREAST CANCER | 2020年 / 6卷 / 01期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/s41523-020-0159-x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

In silico predictions of missense variants is an important consideration when interpreting variants of uncertain significance (VUS) in the BRCA1 and BRCA2 genes. We trained and evaluated hundreds of machine learning algorithms based on results from validated functional assays to better predict missense variants in these genes as damaging or neutral. This new optimal "BRCA-ML" model yielded a substantially more accurate method than current algorithms for interpreting the functional impact of variants in these genes, making BRCA-ML a valuable addition to data sources for VUS classification.

引用

页数：4

共 10 条

[1] PERCH: A Unified Framework for Disease Gene Prioritization
Feng, Bing-Jian
[J]. HUMAN MUTATION, 2017, 38 (03) : 243 - 251
[2] Impact of amino acid substitutions at secondary structures in the BRCT domains of the tumor suppressor BRCA1: Implications for clinical annotation
Fernandes, Vanessa C.
Golubeva, Volha A.
Di Pietro, Giuliano
Shields, Cara
Amankwah, Kwabena
Nepomuceno, Thales C.
de Gregoriis, Giuliana
Abreu, Renata B. V.
Harro, Carly
Gomes, Thiago T.
Silva, Ricceli F.
Suarez-Kurtz, Guilherme
Couch, Fergus J.
Iversen, Edwin S.
Monteiro, Alvaro N. A.
Carvalho, Marcelo A.
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2019, 294 (15) : 5980 - 5992
[3] Accurate classification of BRCA1 variants with saturation genome editing
Findlay, Gregory M.
Daza, Riza M.
Martin, Beth
Zhang, Melissa D.
Leith, Anh P.
Gasperini, Molly
Janizek, Joseph D.
Huang, Xingfan
Starita, Lea M.
Shendure, Jay
[J]. NATURE, 2018, 562 (7726) : 217 - +
[4] Hart S. N., 2020, PREDICTION FUNCTIONA, DOI [10.6084/m9.figshare.12018429, DOI 10.6084/M9.FIGSHARE.12018429]
[5] Comprehensive annotation of BRCA1 and BRCA2 missense variants by functionally validated sequence-based computational prediction models
Hart, Steven N.
Hoskin, Tanya
Shimelis, Hermela
Moore, Raymond M.
Feng, Bingjian
Thomas, Abigail
Lindor, Noralane M.
Polley, Eric C.
Goldgar, David E.
Iversen, Edwin
Monteiro, Alvaro N. A.
Suman, Vera J.
Couch, Fergus J.
[J]. GENETICS IN MEDICINE, 2019, 21 (01) : 71 - 80
[6] The Biological Reference Repository (BioR): a rapid and flexible system for genomics annotation
Kocher, Jean-Pierre A.
Quest, Daniel J.
Duffy, Patrick
Meiners, Michael A.
Moore, Raymond M.
Rider, David
Hossain, Asif
Hart, Steven N.
Dinu, Valentin
[J]. BIOINFORMATICS, 2014, 30 (13) : 1920 - 1922
[7] dbNSFP v3.0: A One-Stop Database of Functional Predictions and Annotations for Human Nonsynonymous and Splice-Site SNVs
Liu, Xiaoming
Wu, Chunlei
Li, Chang
Boerwinkle, Eric
[J]. HUMAN MUTATION, 2016, 37 (03) : 235 - 241
[8] Olsony RS, 2018, BIOCOMPUT-PAC SYM, P192
[9] A Multiplex Homology-Directed DNA Repair Assay Reveals the Impact of More Than 1,000 BRCA1 Missense Substitution Variants on Protein Function
Starita, Lea M.
Islam, Muhtadi M.
Banerjee, Tapahsama
Adamovich, Aleksandra I.
Gullingsrud, Justin
Fields, Stanley
Shendure, Jay
Parvin, Jeffrey D.
[J]. AMERICAN JOURNAL OF HUMAN GENETICS, 2018, 103 (04) : 498 - 508
[10] Classification of Rare Missense Substitutions, Using Risk Surfaces, With Genetic- and Molecular-Epidemiology Applications
Tavtigian, Sean V.
Byrnes, Graham B.
Goldgar, David E.
Thomas, Alun
[J]. HUMAN MUTATION, 2008, 29 (11) : 1342 - 1354

← 1 →