title: HIVE-heptagon: A sensible variant-calling algorithm with post-alignment quality controls.
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.
  
  
  
  https://hive.biochemistry.gwu.edu/.
authors.affiliation: Center for Biologics Evaluation and Research, US Food and Drug Administration, 10993 New Hampshire Ave., Silver Spring, MD, United States. Electronic address: Vahan.simonyan@fda.hhs.gov.
authors.forename: Vahan
authors.initials: V
authors.lastname: Simonyan
authors.affiliation: Center for Biologics Evaluation and Research, US Food and Drug Administration, 10993 New Hampshire Ave., Silver Spring, MD, United States. Electronic address: Konstantin.Chumakov@fda.hhs.gov.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Chumakov
authors.affiliation: Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, 10993 New Hampshire Ave., United States. Electronic address: Eric.Donaldson@fda.hhs.gov.
authors.forename: Eric
authors.initials: E
authors.lastname: Donaldson
authors.affiliation: 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: Konstantinos.Karagiannis@fda.hhs.gov.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Karagiannis
authors.affiliation: Center for Biologics Evaluation and Research, US Food and Drug Administration, 10993 New Hampshire Ave., Silver Spring, MD, United States. Electronic address: LamPhuc.VinhNguyen@fda.hhs.gov.
authors.forename: Phuc VinhNguyen
authors.initials: PV
authors.lastname: Lam
authors.affiliation: 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: Dingerdissen@fda.hhs.gov.
authors.forename: Hayley
authors.initials: H
authors.lastname: Dingerdissen
authors.affiliation: Center for Biologics Evaluation and Research, US Food and Drug Administration, 10993 New Hampshire Ave., Silver Spring, MD, United States. Electronic address: Alin.Voskanian-Kordi@fda.hhs.gov.
authors.forename: Alin
authors.initials: A
authors.lastname: Voskanian
mesh_terms: D000465:Algorithms; D015894:Genome, Human; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D011110:Polymorphism, Genetic; D011786:Quality Control; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA / Q000379:methods
keywords: Genome assembly; HTS; NGS; Post-alignment quality control; SNP; Variant-calling