HIVE-heptagon: A sensible variant-calling algorithm with post-alignment quality controls

Vahan Simonyan; Konstantin Chumakov; Eric Donaldson; Konstantinos Karagiannis; Phuc VinhNguyen Lam; Hayley Dingerdissen; Alin Voskanian

doi:10.1016/j.ygeno.2017.01.002

HIVE-heptagon: A sensible variant-calling algorithm with post-alignment quality controls

Genomics. 2017 Jul;109(3-4):131-140. doi: 10.1016/j.ygeno.2017.01.002. Epub 2017 Feb 8.

Authors

Vahan Simonyan¹, Konstantin Chumakov², Eric Donaldson³, Konstantinos Karagiannis⁴, Phuc VinhNguyen Lam⁵, Hayley Dingerdissen⁶, Alin Voskanian⁷

Affiliations

¹ Center for Biologics Evaluation and Research, US Food and Drug Administration, 10993 New Hampshire Ave., Silver Spring, MD, United States. Electronic address: [email protected].
² Center for Biologics Evaluation and Research, US Food and Drug Administration, 10993 New Hampshire Ave., Silver Spring, MD, United States. Electronic address: [email protected].
³ Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, 10993 New Hampshire Ave., United States. Electronic address: [email protected].
⁴ Center for Biologics Evaluation and Research, US Food and Drug Administration, 10993 New Hampshire Ave., Silver Spring, MD, United States; Department of Biochemistry and Molecular Medicine, George Washington University Medical Center, 2300 Eye St. NW, Washington DC, United States. Electronic address: [email protected].
⁵ Center for Biologics Evaluation and Research, US Food and Drug Administration, 10993 New Hampshire Ave., Silver Spring, MD, United States. Electronic address: [email protected].
⁶ Center for Biologics Evaluation and Research, US Food and Drug Administration, 10993 New Hampshire Ave., Silver Spring, MD, United States; Department of Biochemistry and Molecular Medicine, George Washington University Medical Center, 2300 Eye St. NW, Washington DC, United States. Electronic address: [email protected].
⁷ Center for Biologics Evaluation and Research, US Food and Drug Administration, 10993 New Hampshire Ave., Silver Spring, MD, United States. Electronic address: [email protected].

PMID: 28188908
DOI: 10.1016/j.ygeno.2017.01.002

Abstract

Advances in high-throughput sequencing (HTS) technologies have greatly increased the availability of genomic data and potential discovery of clinically significant genomic variants. However, numerous issues still exist with the analysis of these data, including data complexity, the absence of formally agreed upon best practices, and inconsistent reproducibility. Toward a more robust and reproducible variant-calling paradigm, we propose a series of selective noise filtrations and post-alignment quality control (QC) techniques that may reduce the rate of false variant calls. We have implemented both novel and refined post-alignment QC mechanisms to augment existing pre-alignment QC measures. These techniques can be used independently or in combination to identify and correct issues caused during data generation or early analysis stages. The adoption of these procedures by the broader scientific community is expected to improve the identification of clinically significant variants both in terms of computational efficiency and in the confidence of the results.

Availability: https://hive.biochemistry.gwu.edu/.

Keywords: Genome assembly; HTS; NGS; Post-alignment quality control; SNP; Variant-calling.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural

MeSH terms

Algorithms*
Genome, Human*
Genomics / methods
High-Throughput Nucleotide Sequencing / methods*
Humans
Polymorphism, Genetic*
Quality Control*
Reproducibility of Results
Sequence Analysis, DNA / methods