Congruency in the prediction of pathogenic missense mutations: State-of-the-art web-based tools

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

A remarkable degree of genetic variation has been found in the protein-encoding regions of DNA through deep sequencing of samples obtained from thousands of subjects from several populations. Approximately half of the 20 000 single nucleotide polymorphisms present, even in normal healthy subjects, are nonsynonymous amino acid substitutions that could potentially affect protein function. The greatest challenges currently facing investigators are data interpretation and the development of strategies to identify the few gene-coding variants that actually cause or confer susceptibility to disease. A confusing array of options is available to address this problem. Unfortunately, the overall accuracy of these tools at ultraconserved positions is low, and predictions generated by current computational tools may mislead researchers involved in downstream experimental and clinical studies. First, we have presented an updated review of these tools and their primary functionalities, focusing on those that are naturally prone to analyze massive variant sets, to infer some interesting similarities among their results. Additionally, we have evaluated the prediction congruency for real whole-exome sequencing data in a proof-of-concept study on some of these web-based tools.

Original languageEnglish
Article numberbbt013
Pages (from-to)448-459
Number of pages12
JournalBriefings in Bioinformatics
Volume14
Issue number4
DOIs
Publication statusPublished - Jul 2013

Fingerprint

Missense Mutation
Research Personnel
Exome
High-Throughput Nucleotide Sequencing
Disease Susceptibility
Amino Acid Substitution
Single Nucleotide Polymorphism
Healthy Volunteers
Proteins
DNA
Nucleotides
Polymorphism
Population
Genes
Amino acids
Substitution reactions
Clinical Studies

Keywords

  • Nonsynonymous SNP
  • Pathological effect
  • SNP classification
  • Whole-exome sequencing

ASJC Scopus subject areas

  • Molecular Biology
  • Information Systems

Cite this

Congruency in the prediction of pathogenic missense mutations : State-of-the-art web-based tools. / Castellana, Stefano; Mazza, Tommaso.

In: Briefings in Bioinformatics, Vol. 14, No. 4, bbt013, 07.2013, p. 448-459.

Research output: Contribution to journalArticle

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