Regsnps: A strategy for prioritizing regulatory single nucleotide substitutions

Mingxiang Teng, Shoji Ichikawa, Leah R. Padgett, Yadong Wang, Matthew Mort, David N. Cooper, Daniel L. Koller, Tatiana Foroud, Howard J. Edenberg, Michael J. Econs, Yunlong Liu

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Motivation: One of the fundamental questions in genetics study is to identify functional DNA variants that are responsible to a disease or phenotype of interest. Results from large-scale genetics studies, such as genome-wide association studies (GWAS), and the availability of high-throughput sequencing technologies provide opportunities in identifying causal variants. Despite the technical advances, informatics methodologies need to be developed to prioritize thousands of variants for potential causative effects.Results: We present regSNPs, an informatics strategy that integrates several established bioinformatics tools, for prioritizing regulatory SNPs, i.e. the SNPs in the promoter regions that potentially affect phenotype through changing transcription of downstream genes. Comparing to existing tools, regSNPs has two distinct features. It considers degenerative features of binding motifs by calculating the differences on the binding affinity caused by the candidate variants and integrates potential phenotypic effects of various transcription factors. When tested by using the disease-causing variants documented in the Human Gene Mutation Database, regSNPs showed mixed performance on various diseases. regSNPs predicted three SNPs that can potentially affect bone density in a region detected in an earlier linkage study. Potential effects of one of the variants were validated using luciferase reporter assay.

Original languageEnglish (US)
Article numberbts275
Pages (from-to)1879-1886
Number of pages8
JournalBioinformatics
Volume28
Issue number14
DOIs
StatePublished - Jul 1 2012

Fingerprint

Nucleotides
Single Nucleotide Polymorphism
Substitution
Informatics
Substitution reactions
Genes
Phenotype
Integrate
Gene
Transcription factors
Genome-Wide Association Study
Transcription
Bioinformatics
Transcription Factor
Computational Biology
Luciferases
Bone
Genetic Promoter Regions
Promoter
Bone Density

ASJC Scopus subject areas

  • Statistics and Probability
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Computational Mathematics

Cite this

Teng, M., Ichikawa, S., Padgett, L. R., Wang, Y., Mort, M., Cooper, D. N., ... Liu, Y. (2012). Regsnps: A strategy for prioritizing regulatory single nucleotide substitutions. Bioinformatics, 28(14), 1879-1886. [bts275]. https://doi.org/10.1093/bioinformatics/bts275

Regsnps : A strategy for prioritizing regulatory single nucleotide substitutions. / Teng, Mingxiang; Ichikawa, Shoji; Padgett, Leah R.; Wang, Yadong; Mort, Matthew; Cooper, David N.; Koller, Daniel L.; Foroud, Tatiana; Edenberg, Howard J.; Econs, Michael J.; Liu, Yunlong.

In: Bioinformatics, Vol. 28, No. 14, bts275, 01.07.2012, p. 1879-1886.

Research output: Contribution to journalArticle

Teng, M, Ichikawa, S, Padgett, LR, Wang, Y, Mort, M, Cooper, DN, Koller, DL, Foroud, T, Edenberg, HJ, Econs, MJ & Liu, Y 2012, 'Regsnps: A strategy for prioritizing regulatory single nucleotide substitutions', Bioinformatics, vol. 28, no. 14, bts275, pp. 1879-1886. https://doi.org/10.1093/bioinformatics/bts275
Teng M, Ichikawa S, Padgett LR, Wang Y, Mort M, Cooper DN et al. Regsnps: A strategy for prioritizing regulatory single nucleotide substitutions. Bioinformatics. 2012 Jul 1;28(14):1879-1886. bts275. https://doi.org/10.1093/bioinformatics/bts275
Teng, Mingxiang ; Ichikawa, Shoji ; Padgett, Leah R. ; Wang, Yadong ; Mort, Matthew ; Cooper, David N. ; Koller, Daniel L. ; Foroud, Tatiana ; Edenberg, Howard J. ; Econs, Michael J. ; Liu, Yunlong. / Regsnps : A strategy for prioritizing regulatory single nucleotide substitutions. In: Bioinformatics. 2012 ; Vol. 28, No. 14. pp. 1879-1886.
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