VPOT: A Customizable Variant Prioritization Ordering Tool for Annotated Variants

Eddie Ip; Gavin Chapman; David Winlaw; Sally L Dunwoodie; Eleni Giannoulatou

doi:10.1016/j.gpb.2019.11.001

VPOT: A Customizable Variant Prioritization Ordering Tool for Annotated Variants

Genomics Proteomics Bioinformatics. 2019 Oct;17(5):540-545. doi: 10.1016/j.gpb.2019.11.001. Epub 2019 Nov 22.

Authors

Eddie Ip¹, Gavin Chapman¹, David Winlaw², Sally L Dunwoodie³, Eleni Giannoulatou⁴

Affiliations

¹ Victor Chang Cardiac Research Institute, Sydney 2010, Australia; St Vincent's Clinical School, University of New South Wales, Sydney 2052, Australia.
² Heart Centre for Children, The Children's Hospital at Westmead, Sydney 2145, Australia; Sydney Medical School, University of Sydney, Sydney 2050, Australia.
³ Victor Chang Cardiac Research Institute, Sydney 2010, Australia; St Vincent's Clinical School, University of New South Wales, Sydney 2052, Australia; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney 2033, Australia.
⁴ Victor Chang Cardiac Research Institute, Sydney 2010, Australia; St Vincent's Clinical School, University of New South Wales, Sydney 2052, Australia. Electronic address: e.giannoulatou@victorchang.edu.au.

Abstract

Next-generation sequencing (NGS) technologies generate thousands to millions of genetic variants per sample. Identification of potential disease-causal variants is labor intensive as it relies on filtering using various annotation metrics and consideration of multiple pathogenicity prediction scores. We have developed VPOT (variant prioritization ordering tool), a python-based command line tool that allows researchers to create a single fully customizable pathogenicity ranking score from any number of annotation values, each with a user-defined weighting. The use of VPOT can be informative when analyzing entire cohorts, as variants in a cohort can be prioritized. VPOT also provides additional functions to allow variant filtering based on a candidate gene list or by affected status in a family pedigree. VPOT outperforms similar tools in terms of efficacy, flexibility, scalability, and computational performance. VPOT is freely available for public use at GitHub (https://github.com/VCCRI/VPOT/). Documentation for installation along with a user tutorial, a default parameter file, and test data are provided.

Keywords: Customizable ranking; Genomic annotation; Next-generation sequencing; Pathogenicity predictions; Variant prioritization.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3-Hydroxyanthranilate 3,4-Dioxygenase / genetics
Algorithms
Databases, Genetic
Exome Sequencing
Heart Diseases / congenital
Heart Diseases / genetics
Humans
Polymorphism, Genetic
User-Computer Interface*

Substances

3-Hydroxyanthranilate 3,4-Dioxygenase