Functional Annotation of Noncoding Sequence Variants

Overview

Journal Nat Methods

Specialties Biomedical Engineering
Pathology

Date 2014 Feb 4

PMID 24487584

Citations 313

Authors

Graham R S Ritchie

Ian Dunham

Eleftheria Zeggini

Paul Flicek

Affiliations

Soon will be listed here.

Abstract

Identifying functionally relevant variants against the background of ubiquitous genetic variation is a major challenge in human genetics. For variants in protein-coding regions, our understanding of the genetic code and splicing allows us to identify likely candidates, but interpreting variants outside genic regions is more difficult. Here we present genome-wide annotation of variants (GWAVA), a tool that supports prioritization of noncoding variants by integrating various genomic and epigenomic annotations.

Citing Articles

Ensemble learning-based predictor for driver synonymous mutation with sequence representation.

Bi C, Shi Y, Xia J, Liang Z, Wu Z, Xu K PLoS Comput Biol. 2025; 21(1):e1012744.

PMID: 39761306 PMC: 11737855. DOI: 10.1371/journal.pcbi.1012744.

Deep learning predicts DNA methylation regulatory variants in specific brain cell types and enhances fine mapping for brain disorders.

Zhou J, Weinberger D, Han S Sci Adv. 2025; 11(1):eadn1870.

PMID: 39742481 PMC: 11691643. DOI: 10.1126/sciadv.adn1870.

Quantifying the regulatory potential of genetic variants via a hybrid sequence-oriented model with SVEN.

Wang Y, Liang N, Gao G Nat Commun. 2024; 15(1):10917.

PMID: 39738063 PMC: 11685779. DOI: 10.1038/s41467-024-55392-7.

Variant Impact Predictor database (VIPdb), version 2: trends from three decades of genetic variant impact predictors.

Lin Y, Menon A, Hu Z, Brenner S Hum Genomics. 2024; 18(1):90.

PMID: 39198917 PMC: 11360829. DOI: 10.1186/s40246-024-00663-z.

scaDA: A novel statistical method for differential analysis of single-cell chromatin accessibility sequencing data.

Zhao F, Ma X, Yao B, Lu Q, Chen L PLoS Comput Biol. 2024; 20(8):e1011854.

PMID: 39093856 PMC: 11324137. DOI: 10.1371/journal.pcbi.1011854.

References

Schmidt D, Wilson M, Ballester B, Schwalie P, Brown G, Marshall A . Five-vertebrate ChIP-seq reveals the evolutionary dynamics of transcription factor binding. Science. 2010; 328(5981):1036-40. PMC: 3008766. DOI: 10.1126/science.1186176. View

Bernstein B, Stamatoyannopoulos J, Costello J, Ren B, Milosavljevic A, Meissner A . The NIH Roadmap Epigenomics Mapping Consortium. Nat Biotechnol. 2010; 28(10):1045-8. PMC: 3607281. DOI: 10.1038/nbt1010-1045. View

Davydov E, Goode D, Sirota M, Cooper G, Sidow A, Batzoglou S . Identifying a high fraction of the human genome to be under selective constraint using GERP++. PLoS Comput Biol. 2010; 6(12):e1001025. PMC: 2996323. DOI: 10.1371/journal.pcbi.1001025. View

Hoffman M, Buske O, Wang J, Weng Z, Bilmes J, Noble W . Unsupervised pattern discovery in human chromatin structure through genomic segmentation. Nat Methods. 2012; 9(5):473-6. PMC: 3340533. DOI: 10.1038/nmeth.1937. View

Hindorff L, Sethupathy P, Junkins H, Ramos E, Mehta J, Collins F . Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci U S A. 2009; 106(23):9362-7. PMC: 2687147. DOI: 10.1073/pnas.0903103106. View

Forbes S, Bindal N, Bamford S, Cole C, Kok C, Beare D . COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer. Nucleic Acids Res. 2010; 39(Database issue):D945-50. PMC: 3013785. DOI: 10.1093/nar/gkq929. View

McLaren W, Pritchard B, Rios D, Chen Y, Flicek P, Cunningham F . Deriving the consequences of genomic variants with the Ensembl API and SNP Effect Predictor. Bioinformatics. 2010; 26(16):2069-70. PMC: 2916720. DOI: 10.1093/bioinformatics/btq330. View

Adzhubei I, Schmidt S, Peshkin L, Ramensky V, Gerasimova A, Bork P . A method and server for predicting damaging missense mutations. Nat Methods. 2010; 7(4):248-9. PMC: 2855889. DOI: 10.1038/nmeth0410-248. View

Gaulton K, Nammo T, Pasquali L, Simon J, Giresi P, Fogarty M . A map of open chromatin in human pancreatic islets. Nat Genet. 2010; 42(3):255-9. PMC: 2828505. DOI: 10.1038/ng.530. View

10.

Musunuru K, Strong A, Frank-Kamenetsky M, Lee N, Ahfeldt T, Sachs K . From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus. Nature. 2010; 466(7307):714-9. PMC: 3062476. DOI: 10.1038/nature09266. View

11.

Schwarz J, Rodelsperger C, Schuelke M, Seelow D . MutationTaster evaluates disease-causing potential of sequence alterations. Nat Methods. 2010; 7(8):575-6. DOI: 10.1038/nmeth0810-575. View

12.

Hoffman M, Ernst J, Wilder S, Kundaje A, Harris R, Libbrecht M . Integrative annotation of chromatin elements from ENCODE data. Nucleic Acids Res. 2012; 41(2):827-41. PMC: 3553955. DOI: 10.1093/nar/gks1284. View

13.

Flicek P, Ahmed I, Amode M, Barrell D, Beal K, Brent S . Ensembl 2013. Nucleic Acids Res. 2012; 41(Database issue):D48-55. PMC: 3531136. DOI: 10.1093/nar/gks1236. View

14.

. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012; 489(7414):57-74. PMC: 3439153. DOI: 10.1038/nature11247. View

15.

Adrianto I, Wen F, Templeton A, Wiley G, King J, Lessard C . Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus. Nat Genet. 2011; 43(3):253-8. PMC: 3103780. DOI: 10.1038/ng.766. View

16.

Harrow J, Frankish A, Gonzalez J, Tapanari E, Diekhans M, Kokocinski F . GENCODE: the reference human genome annotation for The ENCODE Project. Genome Res. 2012; 22(9):1760-74. PMC: 3431492. DOI: 10.1101/gr.135350.111. View

17.

Ernst J, Kellis M . ChromHMM: automating chromatin-state discovery and characterization. Nat Methods. 2012; 9(3):215-6. PMC: 3577932. DOI: 10.1038/nmeth.1906. View

18.

Maurano M, Humbert R, Rynes E, Thurman R, Haugen E, Wang H . Systematic localization of common disease-associated variation in regulatory DNA. Science. 2012; 337(6099):1190-5. PMC: 3771521. DOI: 10.1126/science.1222794. View

19.

Stenson P, Mort M, Ball E, Howells K, Phillips A, Thomas N . The Human Gene Mutation Database: 2008 update. Genome Med. 2009; 1(1):13. PMC: 2651586. DOI: 10.1186/gm13. View

20.

Cooper G, Shendure J . Needles in stacks of needles: finding disease-causal variants in a wealth of genomic data. Nat Rev Genet. 2011; 12(9):628-40. DOI: 10.1038/nrg3046. View