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. 2022 Dec 27;23(1):271.
doi: 10.1186/s13059-022-02840-6.

Truvari: refined structural variant comparison preserves allelic diversity

Adam C English  1 , Vipin K Menon  2 , Richard A Gibbs  2 , Ginger A Metcalf  2 , Fritz J Sedlazeck  2
Affiliations

Truvari: refined structural variant comparison preserves allelic diversity

Adam C English et al. Genome Biol. .

Abstract

The fundamental challenge of multi-sample structural variant (SV) analysis such as merging and benchmarking is identifying when two SVs are the same. Common approaches for comparing SVs were developed alongside technologies which produce ill-defined boundaries. As SV detection becomes more exact, algorithms to preserve this refined signal are needed. Here, we present Truvari-an SV comparison, annotation, and analysis toolkit-and demonstrate the effect of SV comparison choices by building population-level VCFs from 36 haplotype-resolved long-read assemblies. We observe over-merging from other SV merging approaches which cause up to a 2.2× inflation of allele frequency, relative to Truvari.

Keywords: SV annotation; SV benchmarking; SV comparison; SV merging; Structural variation.

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Conflict of interest statement

FJS received research support from PacBio and Oxford Nanopore.

Figures

Fig. 1
Fig. 1
Overview of the Truvari method and comparison metrics. a Schematic illustrating the Truvari bench matching approach of a baseline and comparison (comp) VCF. b–e Comparison metrics used by Truvari to measure similarity
Fig. 2
Fig. 2
Intra-sample merging. a Distributions of similarity metrics of SVs between NA24385 haplotypes. Colors are thresholds for sequence and size similarity. b Effect of stringency on intra-sample merging SV counts for GRCh38. The trend line is the average number of SVs per merge. Separation of samples is attributable to ancestry
Fig. 3
Fig. 3
Merging strategies’ impact on pVCF number of SVs and their allele frequency over Ensembl genes. a Count of deletions and insertions produced by each merging strategy. b Average allele frequency of SVs as merging leniency increases
Fig. 4
Fig. 4
Investigation of tandem repeats to assess merging strategies’ performance. a Illustration of a locus where eight insertion alleles (Input) have between + 2 and + 5 copies of a 29-bp repeat across 10 samples. Four of the alleles are annotated as redundant representations (blue) since they have a counterpart with an equal number of copies (orange). A correct merge would preserve each of the unique alleles and remove all redundant alleles, leaving 0 missing and 0 redundant SVs in the locus. An incorrect merge removes two unique insertions (+ 3, + 4) and leaves 1 redundant insertion. b Boxplot of the number of missing variants per locus for each merging strategy. c Barplot of the number of loci with none or any redundant alleles post-merging
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