ToTem: a tool for variant calling pipeline optimization

• Published in: BMC bioinformatics Vol. 19; no. 1; p. 243
• Main Authors: Tom, Nikola, Tom, Ondrej, Malcikova, Jitka, Pavlova, Sarka, Kubesova, Blanka, Rausch, Tobias, Kolarik, Miroslav, Benes, Vladimir, Bystry, Vojtech, Pospisilova, Sarka
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 26-06-2018; BioMed Central; BMC
• Subjects: Analysis; Artificial intelligence; Automation; Benchmarking; Bioinformatics; C plus plus; Computational Biology - methods; Computer graphics; Data processing; Gene sequencing; Genomes; Genomics; Graphical user interface; High-Throughput Nucleotide Sequencing - methods; High-throughput screening (Biochemical assaying); Leukemia; Mathematical functions; Medical research; Mutation; Next generation sequencing; Optimization; Parameter estimation; Parameter optimization; Parameters; Process controls; Recall; Reproducibility; Reproducibility of Results; Research Design; Software; Variant calling; Web applications; Benchmarking; Parameter optimization; Next generation sequencing; Variant calling
• ISSN: 1471-2105; 1471-2105
• DOI: 10.1186/s12859-018-2227-x

High-throughput bioinformatics analyses of next generation sequencing (NGS) data often require challenging pipeline optimization. The key problem is choosing appropriate tools and selecting the best parameters for optimal precision and recall.
Here we introduce ToTem, a tool for automated pipeline optimization. ToTem is a stand-alone web application with a comprehensive graphical user interface (GUI). ToTem is written in Java and PHP with an underlying connection to a MySQL database. Its primary role is to automatically generate, execute and benchmark different variant calling pipeline settings. Our tool allows an analysis to be started from any level of the process and with the possibility of plugging almost any tool or code. To prevent an over-fitting of pipeline parameters, ToTem ensures the reproducibility of these by using cross validation techniques that penalize the final precision, recall and F-measure. The results are interpreted as interactive graphs and tables allowing an optimal pipeline to be selected, based on the user's priorities. Using ToTem, we were able to optimize somatic variant calling from ultra-deep targeted gene sequencing (TGS) data and germline variant detection in whole genome sequencing (WGS) data.
ToTem is a tool for automated pipeline optimization which is freely available as a web application at  https://totem.software .