ToTem: a tool for variant calling pipeline optimization

BMC Bioinformatics. 2018 Jun 26;19(1):243. doi: 10.1186/s12859-018-2227-x.

Abstract

Background: 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.

Results: 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.

Conclusions: ToTem is a tool for automated pipeline optimization which is freely available as a web application at https://totem.software .

Keywords: Benchmarking; Next generation sequencing; Parameter optimization; Variant calling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computational Biology / methods*
  • High-Throughput Nucleotide Sequencing / methods*
  • Reproducibility of Results
  • Research Design
  • Software