| Title: | TinkerHap - A Novel Read-Based Phasing Algorithm with Integrated Multi-Method Support for Enhanced Accuracy |
| Journal: | GigaScience |
| Published: | 28 Oct 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41147705/ |
| DOI: | https://doi.org/10.1093/gigascience/giaf138 |
| URL: | https://academic.oup.com/gigascience/advance-article-pdf/doi/10.1093/gigascience/giaf138/65003814/giaf138.pdf |
Publication 16628
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Abstract
Phasing, the assignment of alleles to their respective parental chromosomes, is fundamental to studying genetic variation and identifying disease-causing variants. Traditional approaches, including statistical, pedigree-based, and read-based phasing, face challenges such as limited accuracy for rare variants and reliance on external reference panels. To address these limitations, we developed TinkerHap, a novel phasing algorithm that integrates a read-based phaser, based on a pairwise distance-based unsupervised classification, with external phased data, such as statistical or pedigree phasing. We evaluated TinkerHap's performance against other phasing algorithms using 1,040 parent-offspring trios from the UK Biobank (Illumina short-reads) and GIAB Ashkenazi trio (PacBio long-reads). TinkerHap's read-based phaser alone achieved higher phasing accuracies than all other algorithms with 95.1% for short-reads (second best: 94.8%) and 97.5% for long-reads (second best: 95.5%). Its hybrid approach further enhanced short-read performance to 96.3% accuracy and was able to phase 99.5% of all heterozygous sites. TinkerHap also extended haplotype block sizes to a median of 79,449 base-pairs for long-reads (second best: 68,303 bp) and demonstrated higher accuracy for both SNPs and indels. This combination of a robust read-based algorithm and hybrid strategy makes TinkerHap a uniquely powerful tool for genomic analyses.</p>
5 Authors
- Uri Hartmann
- Eran Shaham
- Dafna Nathan
- Ilana Blech
- Danny Zeevi
1 Application
| Application ID | Title |
|---|---|
| 74655 | Elucidating the genetic basis of type 1 diabetes |
Enabling scientific discoveries that improve human health