May 7, 2016

Localized structural frustration for evaluating the impact of sequence variants

BioRxiv : the Preprint Server for Biology
Sushant KumarMark Gerstein

Abstract

The rapidly declining costs of sequencing human genomes and exomes are providing deeper insights into genomic variation than previously possible. Growing sequence datasets are uncovering large numbers of rare single-nucleotide variants (SNVs) in coding regions, many of which may even be unique to single individuals. The rarity of such variants makes it difficult to use conventional variant-phenotype associations as a means of predicting their potential impacts. As such, protein structures may help to provide the needed means for inferring otherwise difficult-to-discern rare SNV-phenotype associations. Previous efforts have sought to quantify the effects of SNVs on structures by evaluating their impacts on global stability. However, local perturbations can severely impact functionality (such as catalysis,allosteric regulation, interactions and specificity) without strongly disrupting global stability.Here, we describe a workflow in which localized frustration (which quantifies unfavorable residue-residue interactions) is employed as a metric to investigate such effects. We apply frustration to study the impacts of a large number of SNVs available throughout a number of next-generation sequencing datasets. Most of our observation...Continue Reading

  • References
  • Citations

References

  • We're still populating references for this paper, please check back later.
  • References
  • Citations

Citations

  • This paper may not have been cited yet.

Mentioned in this Paper

Tumor Suppressor Genes
Genome
Nucleic Acid Sequencing
Tsg-5 protein, mouse
Evaluation
Genomics
Sequencing
Massively-Parallel Sequencing
Drug Interactions
Mental Association

About this Paper

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Related Papers

Methods in Molecular Biology
Paul DentPaul B Fisher
Journal of Molecular Biology
Rajini R Haraksingh, Michael P Snyder
Recent Results in Cancer Research. Fortschritte Der Krebsforschung. Progrès Dans Les Recherches Sur Le Cancer
M Ponz de Leon
© 2020 Meta ULC. All rights reserved