Scientific Publications by FDA Staff

Genomics 2017 Jul;109(3-4):131-40

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

Simonyan V, Chumakov K, Donaldson E, Karagiannis K, Lam PV, Dingerdissen H, Voskanian A

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.