{"doi":"10.1101/2025.10.09.678885","title":"Comprehensive benchmarking of somatic mutation detection by the SMaHT Network","abstract":"Somatic mosaicism is increasingly recognized as a fundamental feature of human biology, yet the detection of somatic mutations remains challenging. The SMaHT Network conducted four large-scale benchmarking experiments to evaluate sequencing technologies, experimental approaches, and computational methods for detecting diverse somatic mutations. Cumulative sequencing coverage exceeded 1,000× with short reads and 100-400× with long reads for each of nine analyzed samples. We defined optimal strategies for integrating bulk short- and long-read sequencing for mutation detection and demonstrated that using donor-specific assemblies and human pangenome improved variant calling and extended mutation catalogs to challenging genomic regions. We benchmarked six duplex-seq technologies and showed that single-cell sequencing resolves cell type-specific mutational patterns and heterogeneity. Our results indicate that bulk, single-cell, and duplex analyses are complementary - and leveraging all three provides comprehensive characterization of mosaicism within a tissue. Together, these findings provide a roadmap for accurate, genome-wide somatic mutation discovery and analysis.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":555283,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7317,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":21363,"name":"Alexej Abyzov","orcid":"0000-0001-5405-6729","position":1,"is_corresponding":false},{"id":1454081,"name":"The Somatic Mosaicism across Human Tissues Network (SMaHT)","orcid":null,"position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T02:54:59.329539Z","pmid":"41279200","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}