HipHap: Haplotype Assignment and Confidence Scoring for Diploid Reference Genomes
- 1Dana-Farber Cancer Institute and Harvard University
Abstract
Diploid genome assemblies are now routinely available, but most read aligners were designed for haploid references, which have long been the gold standard. When reads are aligned to a diploid assembly, the aligner sees two nearly identical alignments to either haplotype, thus reducing the mapping quality (MapQ) score to reflect this ambiguity. This can cause downstream tools to discard reads from easily mappable regions. Here, we present HipHap (HIgh- Performance HAPlotype assigner) to resolve this issue by aligning reads to each haplotype assembly separately and assigning each read to its best-supported haplotype. HipHap increased the fraction of reads mapping to the diploid genome with high MapQ, outperforming alignment to either parental haplotype. Additionally, we introduce a haplotype assignment quality score (HapQ) in HipHap to quantify confidence in the haplotype of origin of a read. HipHap is implemented in Rust, supports SAM, BAM, CRAM, and PAF formats, and is freely available at: https://github.com/jheinz27/hiphap.
Related
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BibTeX
@misc{heinz2026hiphap,
title = {{HipHap: Haplotype Assignment and Confidence Scoring for Diploid Reference Genomes}},
author = {J. M. Heinz and M. G. Marin and M. Meyerson and H. Li},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.24.754153},
url = {https://www.biorxiv.org/content/10.64898/2026.09.24.754153v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - HipHap: Haplotype Assignment and Confidence Scoring for Diploid Reference Genomes
AU - J. M. Heinz
AU - M. G. Marin
AU - M. Meyerson
AU - H. Li
PY - 2026
DA - 2026/09/24
PB - bioRxiv
DO - 10.64898/2026.09.24.754153
UR - https://www.biorxiv.org/content/10.64898/2026.09.24.754153v1
AB - Diploid genome assemblies are now routinely available, but most read aligners were designed for haploid references, which have long been the gold standard. When reads are aligned to a diploid assembly, the aligner sees two nearly identical alignments to either haplotype, thus reducing the mapping quality (MapQ) score to reflect this ambiguity. This can cause downstream tools to discard reads from easily mappable regions. Here, we present HipHap (HIgh- Performance HAPlotype assigner) to resolve this issue by aligning reads to each haplotype assembly separately and assigning each read to its best-supported haplotype. HipHap increased the fraction of reads mapping to the diploid genome with high MapQ, outperforming alignment to either parental haplotype. Additionally, we introduce a haplotype assignment quality score (HapQ) in HipHap to quantify confidence in the haplotype of origin of a read. HipHap is implemented in Rust, supports SAM, BAM, CRAM, and PAF formats, and is freely available at: https://github.com/jheinz27/hiphap.
ER -