A synthetic-diploid benchmark for accurate variant calling evaluation

By Heng Li, Jonathan M. Bloom, Y. Farjoun, M. Fleharty, Laura D. Gauthier, Benjamin M. Neale, Daniel G. MacArthur. 2018

209 citations recorded by the source corpus.

Existing benchmark datasets for use in evaluating variant-calling accuracy are constructed from a consensus of known short-variant callers, and they are thus biased toward easy regions that are accessible by these algorithms. We derived a new benchmark dataset from the de novo PacBio assemblies of two fully homozygous human cell lines, which provides a relatively more accurate and less biased estimate of small-variant-calling error rates in a realistic context. The synthetic-diploid (Syndip) benchmark dataset, constructed from two fully homozygous long-read assemblies, provides more accurate assessments of error rates in small-variant-calling algorithms than existing benchmarks.

Subfields: Molecular Biology, Plant Science

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. Heng Li
2. Steven L. Salzberg
3. Sergey Koren
4. Adam M. Phillippy
5. Michael C. Schatz
6. Brian Walenz
7. Mihai Pop
8. Richard Durbin

In Plant Science

1. Heng Li
2. Sergey Koren
3. Adam M. Phillippy
4. Steven L. Salzberg
5. Michael C. Schatz
6. Pavel A. Pevzner
7. Brian Walenz
8. Arang Rhie

Citations in the corpus

• Accurate circular consensus long-read sequencing improves variant detection and assembly of a human genome (2019, methodology): “Structural variants in the maternal and paternal Canu and FALCON assemblies from CCS reads (see “De novo assembly”) were called using a previously described workflow 52 .”
• New strategies to improve minimap2 alignment accuracy (2021, unknown): “3 (Li et al., 2018) for HG002 assemblies (AC: GCA 018852605.1 and GCA 018852615.1) and compared to the GIAB truth (Zook et al., 2020) using “truvari -r 2000 -s 1000 -”
• The design and construction of reference pangenome graphs with minigraph (2020, methodology): “We mapped short reads used in [4] with minimap2 and called variants with GATK v4.”
• Best practices for variant calling in clinical sequencing (2020, background): “For example, the synthetic diploid (Syndip) dataset is derived from de novo long-read assemblies of two homozygous human cell lines and aims to provide a less biased view of variant calling accuracy genome-wide [71].”
• A draft human pangenome reference (2022, unknown): “2.4) (Li et al., 2018).”
• The complete sequence of a human genome (2021, background): “com/lh3/dipcall) (65), through direct alignment of the CHM13 v1.”