Biology subjects

Mainzer, L. S.

Publications and source records attributed to Mainzer, L. S..

5 recordsLinked to original sources

bioRxiv2021

Design considerations for workflow management systems use in production genomics research and the clinic

BackgroundThe changing landscape of genomics research and clinical practice has created a need for computational pipelines capable of efficiently orchestrating complex analysis stages while handling large volumes of data across heterogeneous computational environments. Workflow Management Systems (WfMSs) are the software components employed to fill this gap. ResultsThis work provides an approach and systematic evaluation of key features of popular bioinformatics WfMSs in use today: Nextflow, CWL, and WDL and some of their executors, along with Swift/T, a workflow manager commonly used in high-scale physics applications. We employed two use cases: a variant-calling genomic pipeline and a scalability-testing framework, where both were run locally, on an HPC cluster, and in the cloud. This allowed for evaluation of those four WfMSs in terms of language expressiveness, modularity, scalability, robustness, reproducibility, interoperability, ease of development, along with adoption and usage in research labs and healthcare settings. This article is trying to answer, "which WfMS should be chosen for a given bioinformatics application regardless of analysis type?". ConclusionsThe choice of a given WfMS is a function of both its intrinsic language and engine features. Within bioinformatics, where analysts are a mix of dry and wet lab scientists, the choice is also governed by collaborations and adoption within large consortia and technical support provided by the WfMS team/community. As the community and its needs continue to evolve along with computational infrastructure, WfMSs will also evolve, especially those with permissive licenses that allow commercial use. In much the same way as the dataflow paradigm and containerization are now well understood to be very useful in bioinformatics applications, we will continue to see innovations of tools and utilities for other purposes, like big data technologies, interoperability, and provenance.

bioinformatics↗

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↗

bioRxiv2018

Computational performance and accuracy of Sentieon DNASeq variant calling workflow

As reliable, efficient genome sequencing becomes more ubiquitous, the need for similarly reliable and efficient variant calling becomes increasingly important. The Genome Analysis Toolkit (GATK), maintained by the Broad Institute, is currently the widely accepted standard for variant calling software. However, alternative solutions may provide faster variant calling without sacrificing accuracy. One such alternative is Sentieon DNASeq, a toolkit analogous to GATK but built on a highly optimized backend. We evaluated the DNASeq single-sample variant calling pipeline in comparison to that of GATK. Our results confirm the near-identical accuracy of the two software packages, showcase perfect scalability and great speed from Sentieon, and describe computational performance considerations for the deployment of Sentieon DNASeq.

bioinformatics↗

bioRxiv2018

Performance benchmarking of GATK3.8 and GATK4

Use of the Genome Analysis Toolkit (GATK) continues to be the standard practice in genomic variant calling in both research and the clinic. Recently the toolkit has been rapidly evolving. Significant computational performance improvements have been introduced in GATK3.8 through collaboration with Intel in 2017. The first release of GATK4 in early 2018 revealed significant rewrites in the code base, as the stepping stone toward a Spark implementation. As the software continues to be a moving target for optimal deployment in highly productive environments, we present a detailed analysis of these improvements, to help the community stay abreast with changes in performance. We re-evaluated the options previously identified as advantageous, such as threading, parallel garbage collection, I/O options and data-level parallelization. Based on our results, we consider the performance and cost trade-offs of using GATK3.8 and GATK4 for different types of analyses.

bioinformatics↗