VarFish - Collaborative and Comprehensive Variant Analysis for Diagnosis and Research

Abstract

VarFish is a user-friendly web application for the quality control, filtering, prioritization, analysis, and user-based annotation of panel and exome variant data for rare disease genetics. It is capable of processing variant call files with single or multiple samples. The variants are automatically annotated with population frequencies, molecular impact, and presence in databases such as ClinVar. Further, it provides support for pathogenicity scores including CADD, MutationTaster, and phenotypic similarity scores. Users can filter variants based on these annotations and presumed inheritance pattern and sort the results by these scores. Filtered variants are listed with their annotations and many useful link-outs to genome browsers, other gene/variant data portals, and external tools for variant assessment. VarFish allows user to create their own annotations including support for variant assessment following ACMG-AMP guidelines. In close collaboration with medical practitioners, VarFish was designed for variant analysis and prioritization in diagnostic and research settings as described in the software's extensive manual. The user interface has been optimized for supporting these protocols. Users can install VarFish on their own in-house servers where it provides additional lab notebook features for collaborative analysis and allows re-analysis of cases, e.g., after update of genotype or phenotype databases.

WiNGS: Widely integrated NGS platform for federated genome analysis

“…Commercial tools, such as Golden Helix (https://www.goldenhelix.com/), genoox (https://www.genoox.com/), GeneGrid [4], or Illumina baseSpace (https://www.illumina.com/products/by-type/informatics-products/basespace-sequence-hub.html), tend to confine customers to the walled garden of the supplier, are often expensive, and can add considerable cost and maintenance overhead. Alternatively, several free or open source tools are available, including VariantDB [21], Highlander (https://sites.uclouvain.be/highlander/), VCF-server [5], VCF.filter [3], Maser [10], VarFish [6], VarAFT [8], CSI NGS Portal [9], and NGS-Logistics [1]. These tools typically provide predefined or user-based annotations and filtering strategies, but can present significant shortcomings with regard to end-to-end functionality or privacy-oriented collaboration.…”