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. 2018 Feb 5;19(1):120.
doi: 10.1186/s12864-018-4508-1.

CoVaCS: a consensus variant calling system

Matteo Chiara  1 , Silvia Gioiosa  2   3 , Giovanni Chillemi  2 , Mattia D'Antonio  2 , Tiziano Flati  2   3 , Ernesto Picardi  3   4 , Federico Zambelli  1 , David Stephen Horner  1 , Graziano Pesole  5   6 , Tiziana Castrignanò  2
Affiliations

CoVaCS: a consensus variant calling system

Matteo Chiara et al. BMC Genomics. .

Abstract

Background: The advent and ongoing development of next generation sequencing technologies (NGS) has led to a rapid increase in the rate of human genome re-sequencing data, paving the way for personalized genomics and precision medicine. The body of genome resequencing data is progressively increasing underlining the need for accurate and time-effective bioinformatics systems for genotyping - a crucial prerequisite for identification of candidate causal mutations in diagnostic screens.

Results: Here we present CoVaCS, a fully automated, highly accurate system with a web based graphical interface for genotyping and variant annotation. Extensive tests on a gold standard benchmark data-set -the NA12878 Illumina platinum genome- confirm that call-sets based on our consensus strategy are completely in line with those attained by similar command line based approaches, and far more accurate than call-sets from any individual tool. Importantly our system exhibits better sensitivity and higher specificity than equivalent commercial software.

Conclusions: CoVaCS offers optimized pipelines integrating state of the art tools for variant calling and annotation for whole genome sequencing (WGS), whole-exome sequencing (WES) and target-gene sequencing (TGS) data. The system is currently hosted at Cineca, and offers the speed of a HPC computing facility, a crucial consideration when large numbers of samples must be analysed. Importantly, all the analyses are performed automatically allowing high reproducibility of the results. As such, we believe that CoVaCS can be a valuable tool for the analysis of human genome resequencing studies. CoVaCS is available at: https://bioinformatics.cineca.it/covacs .

Keywords: Consensus method; Graphical user interface; Variant annotation; Variant calling; Variant prioritization; Web server; Workflow.

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Conflict of interest statement

Ethics approval and consent to participate

The authors testify that this work was performed in accordance with the Declaration of Helsinki and have been approved by the Ethical, Legal and Social Implications (ELSI) Committee of the Istituto di Biomembrane Bioenergetica e Biotecnologie Molecolari, Consiglio Nazionale delle Ricerche, Bari, Italy (Ref. 2017/06/29).

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Schematic of the variant calling pipelines implemented in CoVaCS: Single steps of the pipelines are indicated by capital letters: A to G. Tools are indicated in yellow boxes. a Single sample variant calling, b Joint sample variant calling
Fig. 2
Fig. 2
Comparison of variant calling algorithms on WES data. Sensitivity and specificity, at varying levels of coverage, of variant detection algorithms used in the course of the present study, in the analysis of the golden standard WES benchmark based on the NA12878 platinum genome
Fig. 3
Fig. 3
Comparison of variant calling algorithms on WGS data. Sensitivity and specificity, at high (200X) and low (50X) levels of coverage, of variant detection algorithms used in the present study, for the analysis of the golden standard WGS benchmark based on the NA12878 platinum genome
Fig. 4
Fig. 4
Comparison of variant calling CGES and CoVaCS on regions of low coverage. Comparison of accuracy and specificity levels achieved by the CoVaCS and CGES on genomic regions encompassed by less than 30 uniquely mapping reads, for the WES (A) and WGS (B) data
See this image and copyright information in PMC

References

    1. Chan IS, Ginsburg GS. Personalized medicine: progress and promise. Annu Rev Genomics Hum Genet. 2011;12:217–244. doi: 10.1146/annurev-genom-082410-101446. - DOI - PubMed
    1. Rabbani B, Nakaoka H, Akhondzadeh S, Tekin M, Mahdieh N. Next generation sequencing: implications in personalized medicine and pharmacogenomics. Mol BioSyst. 2016;12(6):1818–1830. doi: 10.1039/C6MB00115G. - DOI - PubMed
    1. Stranneheim H, Wedell A. Exome and genome sequencing: a revolution for the discovery and diagnosis of monogenic disorders. J Intern Med. 2016;279(1):3–15. doi: 10.1111/joim.12399. - DOI - PubMed
    1. UK10K Consortium. (2015). The UK10K project identifies rare variants in health and disease. Nature. 1;526(7571):82–90. - PMC - PubMed
    1. Talenti A, Pierce LCT, Biggs WH, et al. Deep sequencing of 10,000 human genomes. Proc Natl Acad Sci U S A. 2016;113(42):11901–11906. doi: 10.1073/pnas.1613365113. - DOI - PMC - PubMed

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