Variant calling and benchmarking in an era of complete human genome sequences

Published

April 14, 2023

Author(s)

Nathanael David Olson, Justin Wagner, Nathan Dwarshuis, Karen Miga, Marc L. Salit, Justin Zook

Abstract

Genetic variant calling from DNA sequencing has enabled understanding of germline variation in hundreds of thousands of humans. Sequencing technologies and variant-calling methods have advanced rapidly, routinely providing reliable variant calls in most of the human genome. We describe how advances in long reads, deep learning, de novo assembly and pangenomes have expanded access to variant calls in increasingly challenging, repetitive genomic regions, including medically relevant regions, and how new benchmark sets and benchmarking methods illuminate their strengths and limitations. Finally, we explore the possible future of more complete characterization of human genome variation in light of the recent completion of a telomere-to-telomere human genome reference assembly and human pangenomes, and we consider the innovations needed to benchmark their newly accessible repetitive regions and complex variants.

Citation

Nature Reviews Genetics

Pub Type

Journals

Download Paper

https://doi.org/10.1038/s41576-023-00590-0

Local Download

Keywords

genomics, variant calling, benchmarking

Citation

Olson, N. , Wagner, J. , Dwarshuis, N. , Miga, K. , Salit, M. and Zook, J. (2023), Variant calling and benchmarking in an era of complete human genome sequences, Nature Reviews Genetics, [online], https://doi.org/10.1038/s41576-023-00590-0, https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=935532 (Accessed October 13, 2025)