bioRxiv Channel: Somatic Mosaicism across the Human Tissues Network (SMaHT) https://biorxiv.org This feed contains articles for bioRxiv Channel "Somatic Mosaicism across the Human Tissues Network (SMaHT)" bioRxiv bioRxiv https://biorxiv.org <![CDATA[ A personalized multi-platform assessment of somatic mosaicism in the human frontal cortex ]]> https://biorxiv.org/cgi/content/short/2024.12.18.629274v1?rss=1" Zhou, W. Mumm, C. Gan, Y. Switzenberg, J. A. Wang, J. De Oliveira, P. Kathuria, K. Losh, S. J. McDonald, T. L. Bessell, B. Van Deynze, K. McConnell, M. J. Boyle, A. P. Mills, R. E. 2024-12-21 doi:10.1101/2024.12.18.629274 Cold Spring Harbor Laboratory Press 2024-12-21 <![CDATA[ Image-based DNA Sequencing Encoding for Detecting Low-Mosaicism Somatic Mobile Element Insertions ]]> https://biorxiv.org/cgi/content/short/2024.11.07.619809v1?rss=1" Tan, M. Lin, Z. Chen, Z. Park, J. He, Z. Zhou, H. Lee, E. A. Gao, Z. Zhu, X. 2024-11-08 doi:10.1101/2024.11.07.619809 Cold Spring Harbor Laboratory Press 2024-11-08 <![CDATA[ Deaminase-assisted single-molecule and single-cell chromatin fiber sequencing ]]> https://biorxiv.org/cgi/content/short/2024.11.06.622310v1?rss=1" Swanson, E. G. Mao, Y. Mallory, B. J. Vollger, M. R. Ranchalis, J. Bohaczuk, S. C. Parmalee, N. L. Bennett, J. T. Stergachis, A. B. 2024-11-06 doi:10.1101/2024.11.06.622310 Cold Spring Harbor Laboratory Press 2024-11-06 <![CDATA[ Characterization of Cancer Evolution Landscape Based on Accurate Detection of Somatic Mutations in Single Tumor Cells ]]> https://biorxiv.org/cgi/content/short/2023.10.09.561356v1?rss=1" Niu, M. Zhang, Y. Luo, J. Sinson, J. C. Thompson, A. M. Zong, C. 2023-10-09 doi:10.1101/2023.10.09.561356 Cold Spring Harbor Laboratory Press 2023-10-09 <![CDATA[ Multi-platform framework for mapping somatic retrotransposition in human tissues ]]> https://biorxiv.org/cgi/content/short/2025.10.07.680917v1?rss=1" Wang, S. Bae, M. Wang, J. Zhao, B. Nguyen, K. Mallett, S. Switzenberg, J. A. Losh, S. J. Sexton, C. E. Miao, B. Dong, S. Zeng, X. Wang, Z. McDonald, T. L. Mumm, C. Gadde, R. K. Tariq, A. M. Chen, Z. Feng, W. C. Burn, A. Park, J. Chu, C. Shen, H. Wang, T. Urban, A. E. Zhu, X. Li, H. Burns, K. H. Chun, H.-J. E. Park, P. J. SMaHT MEI Working Group, Boyle, A. P. Mills, R. E. Zhou, W. Lee, E. A. 2025-10-07 doi:10.1101/2025.10.07.680917 Cold Spring Harbor Laboratory Press 2025-10-07 <![CDATA[ Comprehensive benchmarking of somatic mutation detection by the SMaHT Network ]]> https://biorxiv.org/cgi/content/short/2025.10.09.678885v1?rss=1" 1,000x short-read and 100-400x long-read data for each of the nine analyzed samples. We determined effective strategies for utilizing short- and long-reads sequencing for mutation detection and demonstrated that using donor-specific assemblies and human pangenome improved calling, extending mutation catalogs to challenging genomic regions. We benchmarked six duplex 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 tissues. Together, these findings provide a roadmap for accurate, genome-wide somatic mutation discovery and analysis. ]]> The Somatic Mosaicism across Human Tissues Network (SMaHT), Abyzov, A. 2025-10-10 doi:10.1101/2025.10.09.678885 Cold Spring Harbor Laboratory Press 2025-10-10 <![CDATA[ A telomere-to-telomere map of somatic mutation burden and functional impact in cancer ]]> https://biorxiv.org/cgi/content/short/2025.10.10.681725v1?rss=1" Sohn, M.-H. Dubocanin, D. Vollger, M. R. Kwon, Y. Minkina, A. Munson, K. M. Hart, S. F. Ranchalis, J. E. Parmalee, N. L. Sedeno-Cortes, A. E. Ou, J. Au, N. Y. Bohaczuk, S. Carroll, B. Frazar, C. D. Harvey, W. T. Hoekzema, K. Huang, M.-F. Jacques, C. N. Jensen, D. M. Kolar, J. T. Lee, R. Lin, J. Loy, K. Mack, T. Mao, Y. Pham, M. M. Ryke, E. Smith, J. D. Sutherlin, L. Swanson, E. G. Weiss, J. M. SMaHT Assembly Working Group, Carvalho, C. Coorens, T. H. Harris, K. Wei, C.-L. Eichler, E. E. Altemose, N. Bennett, J. T. Stergachis, A. B. 2025-10-13 doi:10.1101/2025.10.10.681725 Cold Spring Harbor Laboratory Press 2025-10-13 <![CDATA[ A comprehensive view of somatic mosaicism by single-cell DNA analysis ]]> https://biorxiv.org/cgi/content/short/2025.10.31.685648v1?rss=1" Luquette, L. J. Coorens, T. H. H. Natu, A. Suvakov, M. Caplin, A. Jun, M. S. Mo, A. Pelt, J. Anderson, L. Berselli, M. Bhamidipati, S. Blanchard, T. Brew, J. Chun, H.-J. E. Chun, H. Dehankar, M. K. Feng, W. C. Furatero, R. Grochowski, C. M. Ho, E. Jang, Y. Kottapalli, K. Leonard, M. K. Lim, N. S. Lindsay, T. Nicholson, S. Raimondi, I. Runnels, A. Scharlee, C. Shin, J. Veit, A. D. VonDran, M. Wang, Y. Yuan, D. J. Zhao, Y. Bell, T. J. Ardlie, K. Doddapaneni, H. Fulton, R. Germer, S. Landau, D. Oh, J. W. Park, P. J. Vaccarino, F. M. Walsh, C. A. Abyzov 2025-11-03 doi:10.1101/2025.10.31.685648 Cold Spring Harbor Laboratory Press 2025-11-03 <![CDATA[ Comprehensive benchmarking of somatic single-nucleotide variant and indel detection at ultra-low allele fractions using short- and long-read data ]]> https://biorxiv.org/cgi/content/short/2025.10.13.681545v1?rss=1" 2% VAF SNVs, sensitivity and precision approached [~]80% at [≥]300x, with little gain from additional sequencing. This work provides a comprehensive framework for reliable detection of low-VAF mutations in non-cancer tissues and a valuable resource for the community. ]]> Ha, Y.-J. J. Maziec, D. Markowski, J. Georges, S. J. Parmalee, N. L. Berselli, M. Coorens, T. H. Dong, S. Gardiner, S. Kalra, D. Li, D. Miao, B. Musunuri, R. Xue, L. Yu, Z. Walker, K. Anderson, L. Au, N. Y. Cibulskis, C. Doddapaneni, H. Grochowski, C. M. Jensen, D. M. Lindsay, T. Loy, K. Narayan, A. Narzisi, G. Ou, J. Pham, M. M. Runnels, A. M. Stergachis, A. B. Sutherlin, L. M. Wang, T. Jin, H. Feng, W. C. Zhang, Y. Veit, A. D. Kim, C. T. Chun, H.-J. E. Ardlie, K. Fulton, R. S. Germer, S. Gibbs, R. A. Marth, G. T. Bennett, J. T. Park, P. J. 2025-10-14 doi:10.1101/2025.10.13.681545 Cold Spring Harbor Laboratory Press 2025-10-14 <![CDATA[ Comprehensive benchmarking of somatic structural variant detection at ultra-low allele fractions ]]> https://biorxiv.org/cgi/content/short/2025.09.18.677206v1?rss=1" Zhang, Y. English, A. C. Paulin, L. F. Grochowski, C. M. Maheshwari, S. Mack, T. Berselli, M. Veit, A. D. Fu, Y. SMAHT SV working group, Park, P. J. Sedlazeck, F. J. 2025-09-20 doi:10.1101/2025.09.18.677206 Cold Spring Harbor Laboratory Press 2025-09-20 <![CDATA[ A Pangenomic Method for Establishing a Somatic Variant Detection Resource in HapMap Mixtures ]]> https://biorxiv.org/cgi/content/short/2025.09.29.679336v1?rss=1" 6M single-nucleotide variants, 1.8M small insertions/deletions, 49K structural variations, and 10K mobile element insertions across autosomes, X, and mitochondrial chromosomes. We validated the variants using ultra-deep simulated reads and developed a binomial-based model to estimate coverage requirements for variant detection. Evaluating multiple callers showed CHM13 alignment improves structural variant detection and offers advantages in difficult-to-map regions compared to GRCh38. Systematic characterization showed regions with low detection rate are enriched in centromeres, satellite sequences, tandem repeats, and falsely duplicated genes. This accurate, versatile resource enables systematic evaluation of somatic variant detection technologies. ]]> Kong, N. Tang, Z. Ruttenberg, A. Macias-Velasco, J. F. Li, Z. Zhang, W. Miao, B. Xin, Z. Fu, Q. Park, H. Zhuo, X. Mehinovic, E. Belter, E. Garza, J. E. Dong, S. Casey, E. Johnson, B. K. Majewski, M. F. Palmer, T. Cheng, Y. Lindsay, T. Schedl, T. Li, D. Shen, H. SMaHT Network Assembly/Pangenome Working Group, Fulton, R. Wang, T. Jin, S. C. 2025-10-01 doi:10.1101/2025.09.29.679336 Cold Spring Harbor Laboratory Press 2025-10-01 <![CDATA[ Expanding the Genome in a Bottle Truth Set: Detection and Validation of Novel Low-frequency Variants Using High-accuracy NanoSeq ]]> https://biorxiv.org/cgi/content/short/2025.12.05.692678v1?rss=1" Zhang, Y. Chao, H. Niu, M. Grochowski, C. M. Kottapalli, K. Bhamidipati, S. V. muzny, d. m. Gibbs, R. A. Zong, C. Doddapaneni, H. V. 2025-12-06 doi:10.64898/2025.12.05.692678 Cold Spring Harbor Laboratory Press 2025-12-06 <![CDATA[ MosaicSim: A Novel Mosaic Variant Simulator Reveals Diminishing Returns of Ultra-High Coverage for Mosaic Variant Detection ]]> https://biorxiv.org/cgi/content/short/2025.12.03.692191v1?rss=1" Stricker, E. Jaryani, F. Izydorczyk, M. Poon, C.-L. Sanio, P. Alexander, A. Deb, S. Sedlazeck, F. Rogers, J. Atkinson, E. G. 2025-12-07 doi:10.64898/2025.12.03.692191 Cold Spring Harbor Laboratory Press 2025-12-07 <![CDATA[ Single cell whole genome and transcriptome sequencing links somatic mutations to cell identity and ancestry ]]> https://biorxiv.org/cgi/content/short/2025.10.28.685157v1?rss=1" Natu, A. Dehankar, M. K. Pattni, R. Suvakov, M. Olisov, D. Tomasini, L. Jang, Y. Huang, Y. Benito-Garragori, E. Hasenfeld, P. Korbel, J. Urban, A. E. Abyzov, A. Vaccarino, F. M. 2025-10-29 doi:10.1101/2025.10.28.685157 Cold Spring Harbor Laboratory Press 2025-10-29 <![CDATA[ ToxiTaRGET: a multi-omics resource for toxicant-responsive molecular targets ]]> https://biorxiv.org/cgi/content/short/2025.07.28.667228v1?rss=1" Kumar, R. Fu, T. Kuntala, P. K. Fu, S. Li, D. Bartolomei, M. S. Walker, C. L. Wang, T. Zhang, B. A. 2025-08-02 doi:10.1101/2025.07.28.667228 Cold Spring Harbor Laboratory Press 2025-08-02 <![CDATA[ Long-read MitoScope reveals tissue-resolved somatic mitochondrial variation and landscape of nuclear-embedded mitochondrial sequences ]]> https://biorxiv.org/cgi/content/short/2026.04.13.718259v1?rss=1" 2-fold more NUMTs than short-read surveys--with evidence of nonrandom trinucleotide contexts at breakpoints. These findings expose pervasive, tissue-resolved somatic mtDNA and NUMT instability with direct relevance for variant interpretation, aging, and human disease. ]]> Zakarian, C. Smith, J. D. Wong, C. H. Frazar, C. D. Ryke, E. McGee, S. R. Richardson, M. Weiss, J. M. Munson, K. M. Hoekzema, K. Mack, T. Kwon, Y. Ou, J. Neph, S. J. Sohn, M.-H. Minkina, A. Bennett, J. T. Stergachis, A. B. Eichler, E. E. Wei, C.-L. 2026-04-15 doi:10.64898/2026.04.13.718259 Cold Spring Harbor Laboratory Press 2026-04-15 <![CDATA[ Leveraging Human Pangenome for Improved Somatic Variant Detection ]]> https://biorxiv.org/cgi/content/short/2026.01.04.697580v1?rss=1" Fu, Q. Xin, Z. Miao, B. Zhang, W. Kong, N. Tang, Z. Ruttenberg, A. Albracht, D. Belter, E. A. Garza, J. E. Tomlinson, C. Mehinovic, E. Shen, J. Zhuo, X. Dong, S. Johnson, B. K. Majewski, M. F. Palmer, T. Jang, H. J. Cheng, Y. Li, Z. Lawson, H. A. Lindsay, T. Li, D. Fulton, R. Shen, H. Jin, S. C. SMaHT Network Assembly/Pangenome Working Group, Macias-Velasco, J. F. Wang, T. 2026-01-04 doi:10.64898/2026.01.04.697580 Cold Spring Harbor Laboratory Press 2026-01-04 <![CDATA[ Donor-specific assemblies enhance somatic structural variant detection in complex genomic regions ]]> https://biorxiv.org/cgi/content/short/2026.02.20.707061v1?rss=1" Mack, T. M. Lin, J. Ren, L. Sohn, M.-H. Minkina, A. Kwon, Y. Yoo, D. Sui, Y. Munson, K. M. Hoekzema, K. Mastrorosa, F. K. Sorensen, M. Ayllon, M. Sun, K. A. Koundiya, N. Ou, J. Noyes, M. D. Sedeno-Cortes, A. Leonardson, A. Jacques, C. N. Oliviera, C. Frazar, C. D. Zakarian, C. Jensen, D. M. Swanson, E. G. Ryke, E. Kolar, J. T. Ranchalis, J. Sutherlin, L. Vollger, M. R. Loy, K. Pham, M. M. Huang, M.-F. Au, N. Y. Nielsen, P. M. McGee, S. R. Neph, S. Bohaczuk, S. Shaffer, T. Freeman, V. Mao, Y. Cohen Stillman, B. Richardson, M. Smith, J. D. Weiss, J. M. 2026-02-20 doi:10.64898/2026.02.20.707061 Cold Spring Harbor Laboratory Press 2026-02-20 <![CDATA[ Protamine lacunae preserve the paternal chromatin landscape in sperm ]]> https://biorxiv.org/cgi/content/short/2025.10.03.680364v1?rss=1" Tullius, T. W. Heuer, R. A. Bohaczuk, S. C. Mallory, B. Dubocanin, D. Ranchalis, J. Ayaz, A. Mason, C. Seli, E. Phillippy, A. M. Stergachis, A. Lesch, B. J. 2025-10-05 doi:10.1101/2025.10.03.680364 Cold Spring Harbor Laboratory Press 2025-10-05 <![CDATA[ Benchmarking of duplex sequencing approaches to reveal somatic mutation landscapes ]]> https://biorxiv.org/cgi/content/short/2025.12.12.692823v1?rss=1" View larger version (46K): org.highwire.dtl.DTLVardef@123b221org.highwire.dtl.DTLVardef@83ba0aorg.highwire.dtl.DTLVardef@2b0ab0org.highwire.dtl.DTLVardef@1cae35e_HPS_FORMAT_FIGEXP M_FIG C_FIG ]]> Zhang, Y. Viswanadham, V. Andreopoulos, M. Glodzik, D. Liu, R. Luquette, L. Jo, S.-Y. Narayan, A. Niu, M. Anderson, L. Brew, J. Chao, H. Cibulskis, C. Dong, G. Evani, U. Feng, W. Gronska-Peski, M. Helland, A. Hilal, N. Jabara, N. Jin, H. Li, N. Manam, M. Mallett, S. Runnels, A. Scharlee, C. Smith, C. The SMaHT Duplex Sequencing Working Group, Shao, D. Walsh, C. Adalsteinsson, V. Germer, S. Gibbs, R. Choudhury, S. Doddapaneni, H. Evrony, G. Zong, C. Coorens, T. 2025-12-15 doi:10.64898/2025.12.12.692823 Cold Spring Harbor Laboratory Press 2025-12-15 <![CDATA[ As48, a First-in-Class Dual-Function TREM2 Modulator: Receptor Activation and Shedding Inhibition ]]> https://biorxiv.org/cgi/content/short/2025.08.23.671919v1?rss=1" View larger version (38K): org.highwire.dtl.DTLVardef@1b67c28org.highwire.dtl.DTLVardef@1913034org.highwire.dtl.DTLVardef@f3bf58org.highwire.dtl.DTLVardef@97448a_HPS_FORMAT_FIGEXP M_FIG C_FIG ]]> Cho, S. El gaamouch, F. Upadhyay, S. Nada, H. Kuncewicz, K. Gabr, M. 2025-08-28 doi:10.1101/2025.08.23.671919 Cold Spring Harbor Laboratory Press 2025-08-28 <![CDATA[ Nanopore whole-genome sequencing reveals conserved chromosome-specific telomere architecture across tissues and populations ]]> https://biorxiv.org/cgi/content/short/2025.12.10.693405v1?rss=1" 250 individuals from 1000 Genomes and the SMaHT projects, chromosome-specific telomere length patterns are conserved across individuals and tissues, with tissues from the same individual showing highly similar patterns. This conserved landscape suggests coordinated regulation, whose disruption may contribute to genomic instability. Nanopore sequencing also allows simultaneous detection of structural variants, including disruption of TERT and NHP2 that drive global telomere shortening. Furthermore, our quantification of telomere variant repeats in positional context indicates active telomerase-mediated elongation. Our integrated profiling of telomere length and structural variation enables inference of variant effects on chromosome-specific telomere dynamics and may uncover risk factors for short telomere syndromes and cancer. Importantly, positionally fully resolved telomeric variant repeat patterns may predict activated telomere maintenance mechanisms with high accuracy. SignificanceResolving chromosome-specific telomere length and variant-repeat architecture across tissues and individuals provides a framework to dissect coordinated telomere maintenance, its disruption by genetic variants, and how this shapes telomere mosaicism and disease risk. ]]> Engel, N. L. Brors, B. Feuerbach, L. Park, P. J. 2025-12-12 doi:10.64898/2025.12.10.693405 Cold Spring Harbor Laboratory Press 2025-12-12 <![CDATA[ Integrated map of somatic mosaicism across human tissues in 25 individuals ]]> https://biorxiv.org/cgi/content/short/2026.09.01.748636v1?rss=1" The Somatic Mosaicism across Human Tissues Network, Sedlazeck, F. J. Coorens, T. H. H. Park, P. J. Stergachis, A. B. 2026-09-03 doi:10.64898/2026.09.01.748636 Cold Spring Harbor Laboratory Press 2026-09-03 <![CDATA[ Pansoma, a machine learning tool for identifying somatic variants using pangenome graphs ]]> https://biorxiv.org/cgi/content/short/2026.05.27.726245v1?rss=1" Shen, J. Fu, Q. Macias, J. F. Human Pangenome Reference Consortium, Li, D. Wang, T. 2026-05-29 doi:10.64898/2026.05.27.726245 Cold Spring Harbor Laboratory Press 2026-05-29 <![CDATA[ Short-Read Sequencing Benchmarking with Donor-Specific Assemblies ]]> https://biorxiv.org/cgi/content/short/2026.06.24.734333v1?rss=1" McGee, S. R. Smith, J. D. Frazar, C. D. Ryke, E. Vollger, M. R. Kwon, Y. Bennett, J. T. Eichler, E. E. Stergachis, A. Wei, C.-L. 2026-06-28 doi:10.64898/2026.06.24.734333 Cold Spring Harbor Laboratory Press 2026-06-28 <![CDATA[ Somatic variant detection in normal tissues from single-cell sequencing data ]]> https://biorxiv.org/cgi/content/short/2026.06.10.731451v1?rss=1" Luo, R. Wang, Z. Dou, J. Bhamidipati, S. V. Kalra, D. Grochowski, C. M. Doddapaneni, H. V. Gibbs, R. A. Chen, K. Chen, R. 2026-06-14 doi:10.64898/2026.06.10.731451 Cold Spring Harbor Laboratory Press 2026-06-14 <![CDATA[ MosaicTR: tandem repeat somatic instability quantification from long-read sequencing ]]> https://biorxiv.org/cgi/content/short/2026.03.16.712141v1?rss=1" Kim, J. 2026-03-18 doi:10.64898/2026.03.16.712141 Cold Spring Harbor Laboratory Press 2026-03-18 <![CDATA[ Himito: a Graph-based Toolkit for Mitochondrial Genome Analysis using Long Reads ]]> https://biorxiv.org/cgi/content/short/2025.11.03.686348v1?rss=1" Su, H. Huang, Y. Durham, T. Kong, N. Casey,, E. Benjamin, D. Jin, S. C. Garimella, K. V. 2025-11-05 doi:10.1101/2025.11.03.686348 Cold Spring Harbor Laboratory Press 2025-11-05 <![CDATA[ LongcallD: joint calling and phasing of small, structural and mosaic variants from long reads ]]> https://biorxiv.org/cgi/content/short/2026.03.20.713111v1?rss=1" Gao, Y. Liao, W.-W. Qin, Q. Hall, I. M. Li, H. 2026-03-22 doi:10.64898/2026.03.20.713111 Cold Spring Harbor Laboratory Press 2026-03-22 <![CDATA[ Timing the onset of homologous recombination deficiency before cancer diagnosis ]]> https://biorxiv.org/cgi/content/short/2025.10.17.683157v1?rss=1" Andreopoulos, M. Niu, M. Zhang, Y. Viswanadham, V. V. Gulhan, D. C. Jin, H. Batalini, F. Wulf, G. Zong, C. Park, P. J. Glodzik, D. 2025-10-19 doi:10.1101/2025.10.17.683157 Cold Spring Harbor Laboratory Press 2025-10-19 <![CDATA[ SigFormer: an Attention-Based Framework for Robust Single-Sample Mutational Signature Decomposition ]]> https://biorxiv.org/cgi/content/short/2026.01.20.700228v1?rss=1" Zhang, Y. Niu, M. Zong, C. 2026-01-21 doi:10.64898/2026.01.20.700228 Cold Spring Harbor Laboratory Press 2026-01-21 <![CDATA[ Pangenome discovery and characterization of human protein-coding duplicated genes ]]> https://biorxiv.org/cgi/content/short/2026.08.05.743125v1?rss=1" Ren, L. Yoo, D. Vlajic, K. Dishuck, P. C. Guitart, X. Kwon, Y. Lin, J. Munson, K. M. Hoekzema, K. Stergachis, A. Vollger, M. R. Schweppe, D. K. Eichler, E. E. 2026-08-06 doi:10.64898/2026.08.05.743125 Cold Spring Harbor Laboratory Press 2026-08-06 <![CDATA[ SomaMutDB 2.0: A comprehensive database for exploring somatic mutations and their functional impact in normal human tissues ]]> https://biorxiv.org/cgi/content/short/2025.09.14.676124v1?rss=1" View larger version (39K): org.highwire.dtl.DTLVardef@1c76484org.highwire.dtl.DTLVardef@1984f71org.highwire.dtl.DTLVardef@8789a9org.highwire.dtl.DTLVardef@5ed54a_HPS_FORMAT_FIGEXP M_FIG C_FIG ]]> Shea, A. Sun, S. Kennedy, J. Zhang, L. Vijg, J. Dong, X. 2025-09-17 doi:10.1101/2025.09.14.676124 Cold Spring Harbor Laboratory Press 2025-09-17 <![CDATA[ Cell-type-specific patterns and consequences of somatic mutation in development and aging brain ]]> https://biorxiv.org/cgi/content/short/2025.05.30.656844v1?rss=1" 10,000-fold while eliminating artifactual mutational signatures. When applied to 98%/2% mixed cell lines, Duplex-Multiome identified sSNVs present in 2% of cells with 92% precision and accurately captured known sSNV mutational spectra, while revealing unexpected subclonal lineages. Duplex-Multiome of > 51,400 nuclei from postmortem brain tissue captured sSNV burdens and spectra across all major brain cell types and subtypes, including those difficult to assay by single-cell whole-genome sequencing (scWGS). This revealed for the first time that diverse neuronal and glial cell types show distinct rates and patterns of age-related mutation, while also directly discovering developmental cell lineage relationships. Duplex-Multiome identified clonal sSNVs occurring at increased rates in glia of certain aged brains, as well as clonal sSNVs that correlated with changes in expression of nearby genes, in both neurotypical and autism spectrum disorder (ASD) individuals, directly demonstrating that somatic mutagenesis can contribute to gene expression phenotypes. Duplex-Multiome can be easily adopted into the 10X Multiome protocol and will bridge somatic mosaicism to a wide range of phenotypic readouts across cell types and tissues. ]]> Kriz, A. J. Mao, S. Shao, D. D. Snellings, D. A. Andersen, R. Dong, G. Ma, C. C. Cline, H. E. Huang, A. Y. Lee, E. A. Walsh, C. A. 2025-06-01 doi:10.1101/2025.05.30.656844 Cold Spring Harbor Laboratory Press 2025-06-01 <![CDATA[ A haplotype-resolved view of human gene regulation ]]> https://biorxiv.org/cgi/content/short/2024.06.14.599122v1?rss=1" Vollger, M. R. Swanson, E. G. Neph, S. J. Ranchalis, J. Munson, K. M. Ho, C.-H. Sedeno-Cortes, A. E. Fondrie, W. E. Bohaczuk, S. C. Mao, Y. Parmalee, N. L. Mallory, B. J. Harvey, W. T. Kwon, Y. Garcia, G. H. Hoekzema, K. Meyer, J. G. Cicek, M. Eichler, E. E. Noble, W. S. Witten, D. M. Bennett, J. T. Ray, J. P. Stergachis, A. B. 2024-06-16 doi:10.1101/2024.06.14.599122 Cold Spring Harbor Laboratory Press 2024-06-16 <![CDATA[ Transgenerational transmission of post-zygotic mutations suggests symmetric contribution of first two blastomeres to human germline ]]> https://biorxiv.org/cgi/content/short/2024.06.18.599438v1?rss=1" Jang, Y. Tomasini, L. Bae, T. Szekely, A. Vaccarino, F. M. Abyzov, A. 2024-06-22 doi:10.1101/2024.06.18.599438 Cold Spring Harbor Laboratory Press 2024-06-22 <![CDATA[ Threshold of somatic mosaicism disrupting the brain function ]]> https://biorxiv.org/cgi/content/short/2023.12.30.573716v1?rss=1" Kim, J. Park, S. M. Koh, H. Y. Ko, A. Kang, H.-C. Chang, W. S. Kim, D. S. Lee, J. H. 2023-12-30 doi:10.1101/2023.12.30.573716 Cold Spring Harbor Laboratory Press 2023-12-30