Introduction

PANTHER-PSEP is a new software tool for predicting non-synonymous genetic variants that may play a causal role in human disease. Several previous variant pathogenicity prediction methods have been proposed that quantify evolutionary conservation among homologous proteins from different organisms. PANTHER-PSEP employs a related but distinct metric based on 'evolutionary preservation': homologous proteins are used to reconstruct the likely sequences of ancestral proteins at nodes in a phylogenetic tree, and the history of each amino acid can be traced back in time from its current state to estimate how long that state has been preserved in its ancestors. Here, we describe the PSEP tool, and assess its performance on standard benchmarks for distinguishing disease-associated from neutral variation in humans. On these benchmarks, PSEP outperforms not only previous tools that utilize evolutionary conservation, but also several highly used tools that include multiple other sources of information as well. For predicting pathogenic human variants, the trace back of course starts with a human 'reference' protein sequence, but the PSEP tool can also be applied to predicting deleterious or pathogenic variants in reference proteins from any of the ∼100 other species in the PANTHER database.PANTHER-PSEP is freely available on the web at http://pantherdb.org/tools/csnpScoreForm.jsp Users can also download the command-line based tool at ftp://ftp.pantherdb.org/cSNP_analysis/PSEP/ CONTACT: pdthomas@usc.eduSupplementary data are available at Bioinformatics online.

Publications

  1. PANTHER-PSEP: predicting disease-causing genetic variants using position-specific evolutionary preservation.
    Cite this
    Tang H, Thomas PD, 2016-07-01 - Bioinformatics (Oxford, England)

Credits

  1. Haiming Tang
    Developer

    Division of Bioinformatics, Department of Preventive Medicine, United States of America

  2. Paul D Thomas
    Investigator

    Division of Bioinformatics, Department of Preventive Medicine, United States of America

Community Ratings

UsabilityEfficiencyReliabilityRated By
0 user
Sign in to rate
Summary
AccessionBT000888
Tool TypeApplication
Category
PlatformsLinux/Unix
TechnologiesPerl
User InterfaceTerminal Command Line
Download Count0
Country/RegionUnited States of America
Submitted ByPaul D Thomas