---
title: "LongPhase-TO: tumor-only long-read method for somatic haplotype reconstruction and variant recalib"
id: "biorxiv-8-somatic-haplotype-reconstruction-and-variant-recalibration-from-tumor-only-long"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-8-somatic-haplotype-reconstruction-and-variant-recalibration-from-tumor-only-long"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.14.751225v1?rss=1"
published_at: "2026-09-19T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# LongPhase-TO: tumor-only long-read method for somatic haplotype reconstruction and variant recalib
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-8-somatic-haplotype-reconstruction-and-variant-recalibration-from-tumor-only-long
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.14.751225v1?rss=1)
- **Published At:** 2026-09-19T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study introduces **LongPhase-TO**, a method to reconstruct **somatic haplotypes** and recalibrate somatic variant calls using only tumor long-read sequencing, without a matched normal sample. - LongPhase-TO co-phases germline and somatic alleles in a single graph rather than projecting somatic calls onto germline haplotypes, enabling unified handling of linkage information from long reads. - The algorithm resolves chromosome-scale **loss of heterozygosity (LOH)** and estimates **tumor DNA fraction** internally from patterns of heterozygosity depletion and haplotype imbalance, avoiding an explicit copy-number and ploidy model. - Across eight datasets from six cancer cell lines (including breast, melanoma and lung models), LongPhase-TO increased haplotype block N50 by a median 2.9-fold compared with germline phasers. - LongPhase-TO improved somatic single-nucleotide variant (**SNV**) and **indel** calling when used with existing callers: raising mean F1 for SNVs from 0.55 to 0.62 (with ClairS-TO) and to 0.65 (with DeepSomatic-TO), and for indels from 0.19 to 0.23. - The largest gains in phasing and variant recalibration were observed at low tumor DNA fraction, where distinguishing somatic from germline variants is most challenging. - The method reconstructs megabase-scale somatic haplotypes, leveraging long-read linkage to span large genomic regions affected by LOH. - Competing interests: one author (R.L.) receives research funding from Oxford Nanopore Technologies; other authors declared no competing interests. - Details such as specific implementation parameters, per-dataset metrics, and full validation procedures were reported in the preprint but are not enumerated in this summary.
## Clinical Analysis & Structured Key Points
Somatic haplotype reconstruction and variant recalibration from tumor-only long-read sequencing | bioRxiv Skip to main content New Results Somatic haplotype reconstruction and variant recalibration from tumor-only long-read sequencing Zhen-Yu Chen , Zhenxian Zheng , Ruibang Luo , Hsu-Fen Fu , Yung-Jen Yang , View ORCID Profile Yao-Ting Huang doi: https://doi.org/10.64898/2026.09.14.751225 Zhen-Yu Chen 1 Department of Computer Science and Information Engineering, National Chung Cheng University, Taiwan; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Zhenxian Zheng 2 School of Computing and Data Science, The University of Hong Kong, Hong Kong, China; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ruibang Luo 2 School of Computing and Data Science, The University of Hong Kong, Hong Kong, China; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Hsu-Fen Fu 1 Department of Computer Science and Information Engineering, National Chung Cheng University, Taiwan; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Yung-Jen Yang 3 Department of Computer Science and Information Engineering, National Chung Cheng University Find this author on Google Scholar Find this author on PubMed Search for this author on this site Yao-Ting Huang 1 Department of Computer Science and Information Engineering, National Chung Cheng University, Taiwan; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Yao-Ting Huang For correspondence: ythuang{at}cs.ccu.edu.tw Abstract Info/History Metrics Supplementary material Preview PDF Abstract Separating somatic from germline variants and reconstructing somatic haplotypes are the two central problems of tumor-only cancer genome analysis. Long reads carry the linkage needed to solve both, but chromosome-scale loss of heterozygosity (LOH) and an unknown degree of normal-cell admixture blur the distinction between somatic and germline haplotypes. Here we present LongPhase-TO, the first method to reconstruct somatic haplotypes from a tumor sample alone. Rather than mapping somatic variants onto germline haplotypes, LongPhase-TO co-phases germline and somatic alleles in a unified graph, in which LOH and tumor DNA fraction are resolved internally from heterozygosity depletion and haplotype imbalance rather than a copy-number and ploidy model. Across eight datasets from six cancer cell lines, LongPhase-TO increased haplotype block N50 by a median of 2.9-fold relative to germline phasers. It also consistently improved somatic single-nucleotide variant (SNV) and indel calls from ClairS-TO and DeepSomatic-TO, raising mean F1 from 0.55 to 0.62 and 0.65 for SNVs and from 0.19 to 0.23 for indels, with the largest gains at low tumor DNA fraction. Across breast, melanoma and lung cancer cell lines, LongPhase-TO improves the accuracy of existing somatic callers and reconstructs megabase-scale somatic haplotypes. Competing Interest Statement R.L. receives research funding from Oxford Nanopore Technologies. The other authors declare no competing interests. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Back to top Previous Posted September 19, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Somatic haplotype reconstruction and variant recalibration from tumor-only long-read sequencing Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Somatic haplotype reconstruction and variant recalibration from tumor-only long-read sequencing Zhen-Yu Chen , Zhenxian Zheng , Ruibang Luo , Hsu-Fen Fu , Yung-Jen Yang , Yao-Ting Huang bioRxiv 2026.09.14.751225; doi: https://doi.org/10.64898/2026.09.14.751225 Share This Article: Copy Citation Tools Somatic haplotype reconstruction and variant recalibration from tumor-only long-read sequencing Zhen-Yu Chen , Zhenxian Zheng , Ruibang Luo , Hsu-Fen Fu , Yung-Jen Yang , Yao-Ting Huang bioRxiv 2026.09.14.751225; doi: https://doi.org/10.64898/2026.09.14.751225 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (8013) Biochemistry (18737) Bioengineering (14888) Bioinformatics (44415) Biophysics (22597) Cancer Biology (19722) Cell Biology (26899) Clinical Trials (138) Developmental Biology (13964) Ecology (21005) Epidemiology (2067) Evolutionary Biology (25454) Genetics (16165) Genomics (23505) Immunology (18703) Microbiology (42484) Molecular Biology (18058) Neuroscience (93440) Paleontology (700) Pathology (2977) Pharmacology and Toxicology (5094) Physiology (8114) Plant Biology (15999) Scientific Communication and Education (2095) Synthetic Biology (4560) Systems Biology (10235) Zoology (2391)
## Related Clinical Research

- [Immune-pressure redistribution as a framework for resistance to PD-1/PD-L1 blockade](https://medichelpline.com/clinical-feed/pubmed-42763389.md) (DOI: 10.1186/s12943-026-02786-4)
- [Cancer type–specific chromatin regulator mutations linked to better survival after immune checkpoi](https://medichelpline.com/clinical-feed/medrxiv-17-cancer-type-specific-profiling-of-chromatin-regulator-mutations-identifies.md)
- [Key 2025 Advances in Autologous Cellular Therapy for Melanoma and Solid Tumors](https://medichelpline.com/clinical-feed/pubmed-42734903.md) (DOI: 10.1002/cncr.70612)
- [PD-L1 PET/CT with 89Zr-atezolizumab to assess tumour saturation during atezolizumab therapy](https://medichelpline.com/clinical-feed/british-journal-of-cancer-0-programmed-death-ligand-1-pd-l1-pet-ct-imaging-to-evaluate-tumour-saturation.md)
- [Optimized extraction of hepatic TIF-sEVs and ncRNA profiles for HCC biomarker discovery](https://medichelpline.com/clinical-feed/plos-one-5-optimization-of-extracellular-vesicle-extraction-from-hepatic-tissue.md)

## Navigation
- [← Back to Oncology Feed](https://medichelpline.com/clinical-feed/oncology.md)
- [← All Clinical Specialties](https://medichelpline.com/clinical-feed.md)
## Medical & Regulatory Disclaimer

> [!CAUTION]
> MedicHelpline content is structured for research, educational, and professional discovery purposes. It does not constitute individual medical advice, clinical diagnosis, or treatment recommendations.
> Always verify dosing, contraindications, and regulatory alerts against official product labeling and primary regulatory sources before clinical decision-making.