appreci8: a pipeline for precise variant calling integrating 8 tools

Sarah Sandmann, Mohsen Karimi, Aniek O. de Graaf, Christian Rohde, Stefanie Göllner, Julian Varghese, Jan Ernsting, Gunilla Walldin, Bert A. van der Reijden, Carsten Müller-Tidow, Luca Malcovati, Eva Hellström-Lindberg, Joop H. Jansen, Martin Dugas

Research output: Contribution to journalArticle

Abstract

Motivation: The application of next-generation sequencing in research and particularly in clinical routine requires valid variant calling results. However, evaluation of several commonly used tools has pointed out that not a single tool meets this requirement. False positive as well as false negative calls necessitate additional experiments and extensive manual work. Intelligent combination and output filtration of different tools could significantly improve the current situation. Results: We developed appreci8, an automatic variant calling pipeline for calling single nucleotide variants and short indels by combining and filtering the output of eight open-source variant calling tools, based on a novel artifact- and polymorphism score. Appreci8 was trained on two data sets from patients with myelodysplastic syndrome, covering 165 Illumina samples. Subsequently, appreci8's performance was tested on five independent data sets, covering 513 samples. Variation in sequencing platform, target region and disease entity was considered. All calls were validated by re-sequencing on the same platform, a different platform or expert-based review. Sensitivity of appreci8 ranged between 0.93 and 1.00, while positive predictive value ranged between 0.65 and 1.00. In all cases, appreci8 showed superior performance compared to any evaluated alternative approach. Availability and implementation: Appreci8 is freely available at https://hub.docker.com/r/wwuimi/appreci8/. Sequencing data (BAM files) of the 678 patients analyzed with appreci8 have been deposited into the NCBI Sequence Read Archive (BioProjectID: 388411; https://www.ncbi.nlm.nih.gov/bioproject/PRJNA388411). Supplementary information: Supplementary data are available at Bioinformatics online.

Original languageEnglish
Pages (from-to)4205-4212
Number of pages8
JournalBioinformatics (Oxford, England)
Volume34
Issue number24
DOIs
Publication statusPublished - Dec 15 2018

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ASJC Scopus subject areas

  • Statistics and Probability
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Computational Mathematics

Cite this

Sandmann, S., Karimi, M., de Graaf, A. O., Rohde, C., Göllner, S., Varghese, J., Ernsting, J., Walldin, G., van der Reijden, B. A., Müller-Tidow, C., Malcovati, L., Hellström-Lindberg, E., Jansen, J. H., & Dugas, M. (2018). appreci8: a pipeline for precise variant calling integrating 8 tools. Bioinformatics (Oxford, England), 34(24), 4205-4212. https://doi.org/10.1093/bioinformatics/bty518