Prioritization and functional assessment of noncoding variants associated with complex diseases

Genome Medicine
Lin Zhou, Fangqing Zhao

Abstract

Unraveling functional noncoding variants associated with complex diseases is still a great challenge. We present a novel algorithm, Prioritization And Functional Assessment (PAFA), that prioritizes and assesses the functionality of genetic variants by introducing population differentiation measures and recalibrating training variants. Comprehensive evaluations demonstrate that PAFA exhibits much higher sensitivity and specificity in prioritizing noncoding risk variants than existing methods. PAFA achieves improved performance in distinguishing both common and rare recurrent variants from non-recurrent variants by integrating multiple annotations and metrics. An integrated platform was developed, providing comprehensive functional annotations for noncoding variants by integrating functional genomic data, which can be accessed at http://159.226.67.237:8080/pafa .

References

Jan 11, 2000·Nucleic Acids Research·S T SherryK Sirotkin
Apr 4, 2002·Journal of the National Cancer Institute·Cathy J BradleyCaralee Roberts
May 1, 2004·Nature Genetics·Kevin G BeckerS Alex Wang
Dec 21, 2004·Nucleic Acids Research·Ada HamoshVictor A McKusick
Jul 19, 2005·Genome Research·Adam SiepelDavid Haussler
Dec 24, 2008·Nucleic Acids Research·Guoqing LiJun Wang
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
Jul 9, 2009·Journal of the National Cancer Institute·Kathy S AlbainDawn L Hershman
Oct 13, 2009·The Journal of Rheumatology·Dina Marek-YagelYackov Berkun
Oct 28, 2009·Genome Research·Katherine S PollardAdam Siepel
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Apr 16, 2010·Nature·UNKNOWN International Cancer Genome ConsortiumHuanming Yang
May 8, 2010·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Victoria M ChiaKatherine A McGlynn
Jun 30, 2010·PLoS Genetics·Nicholas ErikssonJoanna Mountain
Feb 11, 2011·Nature·Elaine R Mardis
Jul 2, 2011·Nature·UNKNOWN Cancer Genome Atlas Research Network
Aug 19, 2011·Nature Reviews. Genetics·Gregory M Cooper, Jay Shendure
Nov 24, 2011·Prostate Cancer·Lisa W ChuAnn W Hsing
Jan 18, 2012·Annual Review of Medicine·Claudia Gonzaga-JaureguiRichard A Gibbs
Jul 12, 2012·Journal of Diabetes·Qibin Qi, Frank B Hu
Sep 8, 2012·Nature·UNKNOWN ENCODE Project Consortium
Sep 8, 2012·Genome Research·Jennifer HarrowTim J Hubbard
Nov 23, 2012·Genetics·Mattias JakobssonNoah A Rosenberg
Apr 5, 2013·Annals of the New York Academy of Sciences·Ronald C W Ma, Juliana C N Chan
Nov 26, 2013·European Urology·Ariana ZnaorFreddie Bray
Feb 4, 2014·Nature Methods·Graham R S RitchiePaul Flicek
Mar 29, 2014·Nature·Robin AnderssonAlbin Sandelin
Apr 20, 2014·Methods in Molecular Biology·Arthur Liberzon
Jul 10, 2014·Briefings in Functional Genomics·Aude Saint Pierre, Emmanuelle Génin
Oct 31, 2014·Nucleic Acids Research·Simon A ForbesPeter J Campbell
Nov 28, 2014·Nucleic Acids Research·John D EicherAndrew D Johnson
Jan 30, 2015·Nature Communications·Ching-Yu ChengChiea Chuen Khor
Feb 27, 2015·Nature·Nicola WaddellSean M Grimmond
Jul 15, 2015·Human Molecular Genetics·Feng Zhang, James R Lupski
Oct 4, 2015·Nature·UNKNOWN 1000 Genomes Project ConsortiumGonçalo R Abecasis

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Citations

Nov 18, 2018·Nucleic Acids Research·Xianfeng LiFengbiao Mao
May 1, 2019·The Journal of Clinical Endocrinology and Metabolism·Matthew DapasM Geoffrey Hayes
Oct 14, 2021·Briefings in Bioinformatics·Zhen CaoShihua Zhang

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Methods Mentioned

BETA
RNA-seq
genotyping

Software Mentioned

Tomcat
VSEA
ClinVar
SIFT
gnomAD
FATHMM
GENOMES
JAVA
IT
LIBLINEAR

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