atSNP Search: a web resource for statistically evaluating influence of human genetic variation on transcription factor binding
Abstract Summary Understanding the regulatory roles of non-coding genetic variants has become a central goal for interpreting results of genome-wide association studies. The regulatory significance of the variants may be interrogated by assessing their influence on transcription factor binding. We h...
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| Published in | Bioinformatics Vol. 35; no. 15; pp. 2657 - 2659 |
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| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
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England
Oxford University Press
01.08.2019
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| Abstract | Abstract
Summary
Understanding the regulatory roles of non-coding genetic variants has become a central goal for interpreting results of genome-wide association studies. The regulatory significance of the variants may be interrogated by assessing their influence on transcription factor binding. We have developed atSNP Search, a comprehensive web database for evaluating motif matches to the human genome with both reference and variant alleles and assessing the overall significance of the variant alterations on the motif matches. Convenient search features, comprehensive search outputs and a useful help menu are key components of atSNP Search. atSNP Search enables convenient interpretation of regulatory variants by statistical significance testing and composite logo plots, which are graphical representations of motif matches with the reference and variant alleles. Existing motif-based regulatory variant discovery tools only consider a limited pool of variants due to storage or other limitations. In contrast, atSNP Search users can test more than 37 billion variant-motif pairs with marginal significance in motif matches or match alteration. Computational evidence from atSNP Search, when combined with experimental validation, may help with the discovery of underlying disease mechanisms.
Availability and implementation
atSNP Search is freely available at http://atsnp.biostat.wisc.edu.
Supplementary information
Supplementary data are available at Bioinformatics online. |
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| AbstractList | Understanding the regulatory roles of non-coding genetic variants has become a central goal for interpreting results of genome-wide association studies. The regulatory significance of the variants may be interrogated by assessing their influence on transcription factor binding. We have developed atSNP Search, a comprehensive web database for evaluating motif matches to the human genome with both reference and variant alleles and assessing the overall significance of the variant alterations on the motif matches. Convenient search features, comprehensive search outputs and a useful help menu are key components of atSNP Search. atSNP Search enables convenient interpretation of regulatory variants by statistical significance testing and composite logo plots, which are graphical representations of motif matches with the reference and variant alleles. Existing motif-based regulatory variant discovery tools only consider a limited pool of variants due to storage or other limitations. In contrast, atSNP Search users can test more than 37 billion variant-motif pairs with marginal significance in motif matches or match alteration. Computational evidence from atSNP Search, when combined with experimental validation, may help with the discovery of underlying disease mechanisms.
atSNP Search is freely available at http://atsnp.biostat.wisc.edu.
Supplementary data are available at Bioinformatics online. Abstract Summary Understanding the regulatory roles of non-coding genetic variants has become a central goal for interpreting results of genome-wide association studies. The regulatory significance of the variants may be interrogated by assessing their influence on transcription factor binding. We have developed atSNP Search, a comprehensive web database for evaluating motif matches to the human genome with both reference and variant alleles and assessing the overall significance of the variant alterations on the motif matches. Convenient search features, comprehensive search outputs and a useful help menu are key components of atSNP Search. atSNP Search enables convenient interpretation of regulatory variants by statistical significance testing and composite logo plots, which are graphical representations of motif matches with the reference and variant alleles. Existing motif-based regulatory variant discovery tools only consider a limited pool of variants due to storage or other limitations. In contrast, atSNP Search users can test more than 37 billion variant-motif pairs with marginal significance in motif matches or match alteration. Computational evidence from atSNP Search, when combined with experimental validation, may help with the discovery of underlying disease mechanisms. Availability and implementation atSNP Search is freely available at http://atsnp.biostat.wisc.edu. Supplementary information Supplementary data are available at Bioinformatics online. SUMMARYUnderstanding the regulatory roles of non-coding genetic variants has become a central goal for interpreting results of genome-wide association studies. The regulatory significance of the variants may be interrogated by assessing their influence on transcription factor binding. We have developed atSNP Search, a comprehensive web database for evaluating motif matches to the human genome with both reference and variant alleles and assessing the overall significance of the variant alterations on the motif matches. Convenient search features, comprehensive search outputs and a useful help menu are key components of atSNP Search. atSNP Search enables convenient interpretation of regulatory variants by statistical significance testing and composite logo plots, which are graphical representations of motif matches with the reference and variant alleles. Existing motif-based regulatory variant discovery tools only consider a limited pool of variants due to storage or other limitations. In contrast, atSNP Search users can test more than 37 billion variant-motif pairs with marginal significance in motif matches or match alteration. Computational evidence from atSNP Search, when combined with experimental validation, may help with the discovery of underlying disease mechanisms. AVAILABILITY AND IMPLEMENTATIONatSNP Search is freely available at http://atsnp.biostat.wisc.edu. SUPPLEMENTARY INFORMATIONSupplementary data are available at Bioinformatics online. |
| Author | Hudson, Rebecca Craven, Mark Shin, Sunyoung Harrison, Christopher Keleş, Sündüz |
| AuthorAffiliation | bty1010-aff3 Department of Computer Sciences, University of Wisconsin-Madison, Madison, WI, USA bty1010-aff4 Department of Statistics, University of Wisconsin-Madison, Madison, WI, USA bty1010-aff1 Department of Mathematical Sciences, University of Texas at Dallas, Richardson, TX, USA bty1010-aff2 Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, USA |
| AuthorAffiliation_xml | – name: bty1010-aff1 Department of Mathematical Sciences, University of Texas at Dallas, Richardson, TX, USA – name: bty1010-aff2 Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, USA – name: bty1010-aff3 Department of Computer Sciences, University of Wisconsin-Madison, Madison, WI, USA – name: bty1010-aff4 Department of Statistics, University of Wisconsin-Madison, Madison, WI, USA |
| Author_xml | – sequence: 1 givenname: Sunyoung surname: Shin fullname: Shin, Sunyoung email: sunyoung.shin@utdallas.edu organization: Department of Mathematical Sciences, University of Texas at Dallas, Richardson, TX, USA – sequence: 2 givenname: Rebecca surname: Hudson fullname: Hudson, Rebecca organization: Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, USA – sequence: 3 givenname: Christopher surname: Harrison fullname: Harrison, Christopher organization: Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, USA – sequence: 4 givenname: Mark surname: Craven fullname: Craven, Mark organization: Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, USA – sequence: 5 givenname: Sündüz surname: Keleş fullname: Keleş, Sündüz email: keles@stat.wisc.edu organization: Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, USA |
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| Cites_doi | 10.1093/nar/gkv1340 10.1093/nar/gkw1064 10.1016/j.hlpt.2012.07.003 10.1093/nar/gkx1020 10.1093/nar/gkt1249 10.1371/journal.pcbi.0040005 10.1093/nar/gkt997 10.1101/gr.137323.112 10.1093/nar/gks1221 10.1093/nar/29.1.308 10.1016/j.tig.2016.10.008 10.1093/bioinformatics/btv328 |
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| Copyright | The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2018 The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. |
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| References_xml | – volume: 44 start-page: D877 year: 2016 ident: 2023062713154272200_bty1010-B12 article-title: HaploReg v4: systematic mining of putative causal variants, cell types, regulators and target genes for human complex traits and disease publication-title: Nucleic Acids Res doi: 10.1093/nar/gkv1340 contributor: fullname: Ward – volume: 45 start-page: D139 year: 2017 ident: 2023062713154272200_bty1010-B6 article-title: SNP2TFBS - a database of regulatory SNPs affecting predicted transcription factor binding site affinity publication-title: Nucleic Acids Res doi: 10.1093/nar/gkw1064 contributor: fullname: Kumar – volume: 1 start-page: 123 year: 2012 ident: 2023062713154272200_bty1010-B1 article-title: UK Biobank: current status and what it means for epidemiology publication-title: Health Policy Technol doi: 10.1016/j.hlpt.2012.07.003 contributor: fullname: Allen – volume: 46 start-page: D762 year: 2017 ident: 2023062713154272200_bty1010-B4 article-title: The UCSC Genome Browser database: 2018 update publication-title: Nucleic Acids Res doi: 10.1093/nar/gkx1020 contributor: fullname: Casper – volume: 42 start-page: 2976 year: 2014 ident: 2023062713154272200_bty1010-B5 article-title: Systematic discovery and characterization of regulatory motifs in ENCODE TF binding experiments publication-title: Nucleic Acids Res doi: 10.1093/nar/gkt1249 contributor: fullname: Kheradpour – volume: 4 start-page: e5. year: 2008 ident: 2023062713154272200_bty1010-B2 article-title: In silico detection of sequence variations modifying transcriptional regulation publication-title: PLoS Comput. Biol doi: 10.1371/journal.pcbi.0040005 contributor: fullname: Andersen – volume: 15 start-page: 485. year: 2014 ident: 2023062713154272200_bty1010-B9 article-title: OncoCis: annotation of cis-regulatory mutations in cancer publication-title: Genome Biol contributor: fullname: Perera – volume: 42 start-page: D142 year: 2014 ident: 2023062713154272200_bty1010-B7 article-title: JASPAR 2014: an extensively expanded and updated open-access database of transcription factor binding profiles publication-title: Nucleic Acids Res doi: 10.1093/nar/gkt997 contributor: fullname: Mathelier – volume: 22 start-page: 1790 year: 2012 ident: 2023062713154272200_bty1010-B3 article-title: Annotation of functional variation in personal genomes using RegulomeDB publication-title: Genome Res doi: 10.1101/gr.137323.112 contributor: fullname: Boyle – volume: 41 start-page: D171 year: 2013 ident: 2023062713154272200_bty1010-B11 article-title: Factorbook. org: a Wiki-based database for transcription factor-binding data generated by the ENCODE consortium publication-title: Nucleic Acids Res doi: 10.1093/nar/gks1221 contributor: fullname: Wang – volume: 29 start-page: 308 year: 2001 ident: 2023062713154272200_bty1010-B10 article-title: dbSNP: the NCBI database of genetic variation publication-title: Nucleic Acids Res doi: 10.1093/nar/29.1.308 contributor: fullname: Sherry – volume: 33 start-page: 34 year: 2017 ident: 2023062713154272200_bty1010-B8 article-title: Mining the unknown: assigning function to noncoding single nucleotide polymorphisms publication-title: Trends Genet doi: 10.1016/j.tig.2016.10.008 contributor: fullname: Nishizaki – volume: 31 start-page: 3353 year: 2015 ident: 2023062713154272200_bty1010-B13 article-title: atSNP: transcription factor binding affinity testing for regulatory SNP detection publication-title: Bioinformatics doi: 10.1093/bioinformatics/btv328 contributor: fullname: Zuo |
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Summary
Understanding the regulatory roles of non-coding genetic variants has become a central goal for interpreting results of genome-wide... Understanding the regulatory roles of non-coding genetic variants has become a central goal for interpreting results of genome-wide association studies. The... SUMMARYUnderstanding the regulatory roles of non-coding genetic variants has become a central goal for interpreting results of genome-wide association studies.... |
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| SubjectTerms | Applications Notes Genetic Variation Genome-Wide Association Study Humans Protein Binding Software Transcription Factors |
| Title | atSNP Search: a web resource for statistically evaluating influence of human genetic variation on transcription factor binding |
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