Kendzior, M. | Search bioRxiv

bioRxiv2020

VarSAn: Associating pathways with a set of genomic variants using network analysis

There is a pressing need today to mechanistically interpret sets of genomic variants associated with diseases. Here we present a tool called VarSAn that uses a network analysis algorithm to identify pathways relevant to a given set of variants. VarSAn analyzes a configurable network whose nodes represent variants, genes and pathways, using a Random Walk with Restarts algorithm to rank pathways for relevance to the given variants, and reports p-values for pathway relevance. It treats non-coding and coding variants differently, properly accounts for the number of pathways impacted by each variant and identifies relevant pathways even if many variants do not directly impact genes of the pathway. We use VarSAn to identify pathways relevant to variants related to cancer and several other diseases, as well as drug response variation. We find VarSAns pathway ranking to be complementary to the standard approach of enrichment tests on genes related to the query set. We adopt a novel benchmarking strategy to quantify its advantage over this baseline approach. Finally, we use VarSAn to discover key pathways, including the VEGFA-VEGFR2 pathway, related to de novo variants in patients of Hypoplastic Left Heart Syndrome, a rare and severe congenital heart defect.

bioinformatics↗

bioRxiv2019

Managing genomic variant calling workflows with Swift/T

Genomic variant discovery is frequently performed using the GATK Best Practices variant calling pipeline, a complex workflow with multiple steps, fans/merges, and conditionals. This complexity makes management of the workflow difficult on a computer cluster, especially when running in parallel on large batches of data: hundreds or thousands of samples at a time. Here we describe a wrapper for the GATK-based variant calling workflow using the Swift/T parallel scripting language. Standard built-in features include the flexibility to split by chromosome before variant calling, optionally permitting the analysis to continue when faulty samples are detected, and allowing users to analyze multiple samples in parallel within each cluster node. The use of Swift/T conveys two key advantages: (1) Thanks to the embedded ability of Swift/T to transparently operate in multiple cluster scheduling environments (PBS Torque, SLURM, Cray aprun environment, etc.,) a single workflow is trivially portable across numerous clusters; (2) The leaf functions of Swift/T permit developers to easily swap executables in and out of the workflow, conditional on the analysts choice, which makes the workflow easy to maintain. This modular design permits separation of the workflow into multiple stages and the request of resources optimal for each stage of the pipeline. While Swift/Ts implicit data-level parallelism eliminates the need for the developer to code parallel analysis of multiple samples, it does make debugging of the workflow a bit more difficult, as is the case with any implicitly parallel code. With the above features, users have a powerful and portable way to scale up their variant calling analysis to run in many traditional computer cluster architectures.\n\nhttps://github.com/ncsa/Swift-T-Variant-Calling\n\nhttp://swift-t-variant-calling.readthedocs.io/en/latest/

bioinformatics↗