{"title":"Cancer Driver Topologically Associated Domains identify oncogenic and tumor suppressive lncRNAs","authors":"Ziyan Rao, Min Zhang, Shaodong Huang, Chenyang Wu, Yuheng Zhou, Weijie Zhang, Xia Lin, Dongyu Zhao","doi":"10.1101/gr.280235.124","DOIUrl":"https://doi.org/10.1101/gr.280235.124","url":null,"abstract":"Cancer long noncoding RNAs (lncRNAs) have been identified by experimental and in silico methods. However, current approaches for identifying cancer lncRNAs are not sufficient and effective. To uncover them, we focused on the core cancer driver lncRNAs, which directly interact with cancer driver protein-coding genes (PCGs). We investigated various aspects of cancer lncRNAs, including their expression patterns, genomic locations, and direct interactions with cancer driver PCGs, and developed a pipeline to unearth candidate cancer driver lncRNAs. Finally, we validated the reliability of potential cancer driver lncRNAs through functional analysis of bioinformatics data and CRISPR-Cas9 knockout experiments. We found that cancer lncRNAs were more concentrated in cancer driver topologically associated domains (CDTs), and CDT is an important feature in identifying cancer lncRNAs. Moreover, cancer lncRNAs showed a high tendency to coexpress with and bind to cancer driver PCGs. Utilizing these distinctive characteristics, we developed a pipeline CADTAD to unearth candidate cancer driver lncRNAs in pan-cancer, including 256 oncogenic lncRNAs, 177 tumor suppressive lncRNAs, and 75 dual-function lncRNAs, as well as in three individual cancer types, and validated their cancer-related function. More importantly, the function of 10 putative cancer driver lncRNAs in prostate cancer was subsequently validated to influence cancer phenotype through cell studies. In light of these findings, our study offers a new perspective from the 3D genome to study the roles of lncRNAs in cancer. Furthermore, we provide a valuable set of potential lncRNAs that could deepen our understanding of the oncogenic mechanism of cancer driver lncRNAs.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"98 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144154227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genome researchPub Date : 2025-05-20DOI: 10.1101/gr.280051.124
Aliza Batya Rubenstein, Gregory R. Smith, Zidong Zhang, Xi Chen, Toby Leigh Chambers, Frederique Ruf-Zamojski, Natalia Mendelev, Wan Sze Cheng, Michel Zamojski, Mary Anne S. Amper, Venugopalan D. Nair, Andrew Reid Marderstein, Stephen B. Montgomery, Olga G. Troyanskaya, Elena Zaslavsky, Todd Trappe, Scott Trappe, Stuart C. Sealfon
{"title":"Integrated single-cell multiome analysis reveals muscle fiber-type gene regulatory circuitry modulated by endurance exercise","authors":"Aliza Batya Rubenstein, Gregory R. Smith, Zidong Zhang, Xi Chen, Toby Leigh Chambers, Frederique Ruf-Zamojski, Natalia Mendelev, Wan Sze Cheng, Michel Zamojski, Mary Anne S. Amper, Venugopalan D. Nair, Andrew Reid Marderstein, Stephen B. Montgomery, Olga G. Troyanskaya, Elena Zaslavsky, Todd Trappe, Scott Trappe, Stuart C. Sealfon","doi":"10.1101/gr.280051.124","DOIUrl":"https://doi.org/10.1101/gr.280051.124","url":null,"abstract":"Endurance exercise induces multi-system adaptations that improve performance and benefit health. Gene regulatory circuit responses within individual skeletal muscle cell types, which are key mediators of exercise effects, have not been studied. We mapped transcriptome, chromatin, and regulatory circuit responses to acute endurance exercise in muscle using same-cell RNA-seq/ATAC-seq multiome assay. High-quality data was obtained from 37,154 nuclei comprising 14 cell types in vastus lateralis samples collected before and 3.5 hours after either 40 min cycling exercise at 70% VO2max or 40 min supine rest. Both shared and cell type specific regulatory programs were identified. Differential gene expression and accessibility sites were largely distinct within nuclei for each cell type and muscle fiber, with the largest numbers of regulatory events observed in the three muscle fiber types (slow, fast, and intermediate) and lumican (LUM) expressing fibro-adipogenic progenitor cells. Single-cell regulatory circuit triad reconstruction (transcription factor, chromatin interaction site, regulated gene) also identified largely distinct gene regulatory circuits modulated by exercise in the three muscle fiber types and LUM-expressing fibro-adipogenic progenitor cells, involving a total of 328 transcription factors acting at chromatin sites regulating 2,025 genes. This web-accessible single-cell dataset and regulatory circuitry map serve as a resource for understanding the molecular underpinnings of the metabolic and physiological effects of exercise and to guide interpretation of the exercise response literature in bulk tissue.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"32 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144104614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genome researchPub Date : 2025-05-20DOI: 10.1101/gr.279380.124
Jianing Yao, Jinglun Yu, Brian Caffo, Stephanie C Page, Keri Martinowich, Stephanie C Hicks
{"title":"Spatial domain detection using contrastive self-supervised learning for spatial multi-omics technologies","authors":"Jianing Yao, Jinglun Yu, Brian Caffo, Stephanie C Page, Keri Martinowich, Stephanie C Hicks","doi":"10.1101/gr.279380.124","DOIUrl":"https://doi.org/10.1101/gr.279380.124","url":null,"abstract":"Recent advances in spatially-resolved single-omics and multi-omics technologies have led to the emergence of computational tools to detect or predict spatial domains. Additionally, histological images and immunofluorescence (IF) staining of proteins and cell types provide multiple perspectives and a more complete understanding of tissue architecture. Here, we introduce Proust, a scalable tool to predict discrete domains using spatial multi-omics data by combining the low-dimensional representation of biological profiles based on graph-based contrastive self-supervised learning. Our scalable method integrates multiple data modalities, such as RNA, protein, and H&E images, and predicts spatial domains within tissue samples. Through the integration of multiple modalities, Proust consistently demonstrates enhanced accuracy in detecting spatial domains, as evidenced across various benchmark datasets and technological platforms.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"397 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144104613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genome researchPub Date : 2025-05-20DOI: 10.1101/gr.279741.124
Kevin W Currin, Hannah J Perrin, Gautam K Pandey, Abdalla A Alkhawaja, Swarooparani Vadlamudi, Annie E Musser, Amy S Etheridge, K Alaine Broadaway, Jonathan D Rosen, Arushi Varshney, Amarjit S Chaudhry, Paul J Gallins, Fred A Wright, Yi-Hui Zhou, Stephen CJ Parker, Laura M. Raffield, Erin G Schuetz, Federico Innocenti, Karen L. Mohlke
{"title":"Genetic effects on chromatin accessibility uncover mechanisms of liver gene regulation and quantitative traits","authors":"Kevin W Currin, Hannah J Perrin, Gautam K Pandey, Abdalla A Alkhawaja, Swarooparani Vadlamudi, Annie E Musser, Amy S Etheridge, K Alaine Broadaway, Jonathan D Rosen, Arushi Varshney, Amarjit S Chaudhry, Paul J Gallins, Fred A Wright, Yi-Hui Zhou, Stephen CJ Parker, Laura M. Raffield, Erin G Schuetz, Federico Innocenti, Karen L. Mohlke","doi":"10.1101/gr.279741.124","DOIUrl":"https://doi.org/10.1101/gr.279741.124","url":null,"abstract":"Chromatin accessibility quantitative trait locus (caQTL) studies have identified regulatory elements that underlie genetic effects on gene expression and metabolic traits. However, caQTL discovery has been limited by small sample sizes. Here, we mapped caQTLs in liver tissue from 138 human donors and identified caQTLs for 35,361 regulatory elements, including population-specific caQTLs driven by differences in allele frequency across populations. We identified 2,126 genetic signals associated with multiple, presumably coordinately regulated elements. Coordinately regulated elements linked distal elements to target genes and were more likely to be associated with gene expression compared to single-element caQTLs. We predicted driver and response elements at coordinated loci and found that driver elements were enriched for transcription factor binding sites of key liver regulators. We identified colocalized caQTLs at 667 genome-wide association (GWAS) signals for metabolic and liver traits and annotated these loci with predicted target genes and disrupted transcription factor binding sites. CaQTLs identified three-fold more GWAS colocalizations than liver expression QTLs (eQTLs) in a larger sample size, suggesting that caQTLs can detect mechanisms missed by eQTLs. At a GWAS signal colocalized with a caQTL and an eQTL for <em>TENM2</em>, we validated regulatory activity for a variant within a predicted driver element that was coordinately regulated with 39 other elements. At another locus, we validated a predicted enhancer of <em>RALGPS2</em> using CRISPR interference and demonstrated allelic effects on transcription for a haplotype within this enhancer. These results demonstrate the power of caQTLs to characterize regulatory mechanisms at GWAS loci.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"15 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144104612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genome researchPub Date : 2025-05-19DOI: 10.1101/gr.280383.124
Dmitry Antipov, Mikko Rautiainen, Sergey Nurk, Brian P Walenz, Steven J Solar, Adam M Phillippy, Sergey Koren
{"title":"Verkko2 integrates proximity ligation data with long-read De Bruijn graphs for efficient telomere-to-telomere genome assembly, phasing, and scaffolding","authors":"Dmitry Antipov, Mikko Rautiainen, Sergey Nurk, Brian P Walenz, Steven J Solar, Adam M Phillippy, Sergey Koren","doi":"10.1101/gr.280383.124","DOIUrl":"https://doi.org/10.1101/gr.280383.124","url":null,"abstract":"The Telomere-to-Telomere Consortium recently finished the first truly complete sequence of a human genome. To resolve the most complex repeats, this project relied on the semi-manual combination of long, accurate PacBio HiFi and ultra-long Oxford Nanopore sequencing reads. The Verkko assembler later automated this process, achieving complete assemblies for approximately half of the chromosomes in a diploid human genome. However, the first version of Verkko was computationally expensive and could not resolve all regions of a typical human genome. Here we present Verkko2, which implements a more efficient read correction algorithm, improves repeat resolution and gap closing, introduces proximity-ligation-based haplotype phasing and scaffolding, and adds support for multiple long-read data types. These enhancements allow Verkko to assemble all regions of a diploid human genome, including the short arms of the acrocentric chromosomes and both sex chromosomes. Together, these changes increase the number of telomere-to-telomere scaffolds by twofold, reduce runtime by fourfold, and improve assembly correctness. On a panel of 19 human genomes, Verkko2 assembles an average of 39 of 46 complete chromosomes as scaffolds, with 21 of these assembled as gapless contigs. Together, these improvements enable telomere-to-telomere comparative genomics and pangenomics, at scale.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"234 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144088315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genome researchPub Date : 2025-05-19DOI: 10.1101/gr.280149.124
Mira Mastoras, Mobin Asri, Lucas Brambrink, Prajna Hebbar, Alexey Kolesnikov, Daniel E. Cook, Maria Nattestad, Julian Lucas, Taylor S. Won, Pi-Chuan Chang, Andrew Carroll, Benedict Paten, Kishwar Shafin
{"title":"Highly accurate assembly polishing with DeepPolisher","authors":"Mira Mastoras, Mobin Asri, Lucas Brambrink, Prajna Hebbar, Alexey Kolesnikov, Daniel E. Cook, Maria Nattestad, Julian Lucas, Taylor S. Won, Pi-Chuan Chang, Andrew Carroll, Benedict Paten, Kishwar Shafin","doi":"10.1101/gr.280149.124","DOIUrl":"https://doi.org/10.1101/gr.280149.124","url":null,"abstract":"Accurate genome assemblies are essential for biological research, but even the highest quality assemblies retain errors caused by the technologies used to construct them. Base-level errors are typically fixed with an additional polishing step that uses reads aligned to the draft assembly to identify necessary edits. However, current methods struggle to find a balance between over- and under-polishing. Here, we present an encoder-only transformer model for assembly polishing called DeepPolisher, which predicts corrections to the underlying sequence using PacBio HiFi read alignments to a diploid assembly. Our pipeline introduces a method, PHARAOH (Phasing Reads in Areas Of Homozygosity), which uses ultra-long ONT data to ensure alignments are accurately phased and to correctly introduce heterozygous edits in falsely homozygous regions. We demonstrate that the DeepPolisher pipeline can reduce assembly errors by approximately half, mostly driven by reductions in indel errors. We have applied our DeepPolisher-based pipeline to 180 assemblies from the next Human Pangenome Reference Consortium (HPRC) data release, producing an average predicted Quality Value (QV) improvement of 3.4 (54% error reduction) for the majority of the genome.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"10 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144088314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genome researchPub Date : 2025-05-15DOI: 10.1101/gr.280090.124
Kavindu Jayasooriya, Sasha P Jenner, Pasindu Marasinghe, Udith Senanayake, Hassaan Saadat, David Taubman, Roshan Ragel, Hasindu Gamaarachchi, Ira W Deveson
{"title":"A new compression strategy to reduce the size of nanopore sequencing data","authors":"Kavindu Jayasooriya, Sasha P Jenner, Pasindu Marasinghe, Udith Senanayake, Hassaan Saadat, David Taubman, Roshan Ragel, Hasindu Gamaarachchi, Ira W Deveson","doi":"10.1101/gr.280090.124","DOIUrl":"https://doi.org/10.1101/gr.280090.124","url":null,"abstract":"Nanopore sequencing is an increasingly central tool for genomics. Despite rapid advances in the field, large data volumes and computational bottlenecks continue to pose major challenges. Here we introduce ex-zd, a new data compression strategy that helps address the large size of raw signal data generated during nanopore experiments. Ex-zd encompasses both a lossless compression method, which modestly outperforms all current methods for nanopore signal data compression, and a 'lossy' method, which can be used to achieve dramatic additional savings. The latter component works by reducing the number of bits used to encode signal data. We show that the three least significant bits in signal data generated on instruments from Oxford Nanopore Technologies (ONT) predominantly encode noise. Their removal reduces file sizes by half without impacting downstream analyses, including basecalling and detection of modified DNA or RNA bases. Ex-zd compression saves hundreds of gigabytes on a single ONT sequencing experiment, thereby increasing the scalability, portability, and accessibility of nanopore sequencing.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"54 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genome researchPub Date : 2025-05-13DOI: 10.1101/gr.279398.124
Xuan Qu, Yonghao Liang, Colin McCornack, Xiaoyun Xing, Heather Schmidt, Chad Tomlinson, Catrina Fronick, Edward A. Belter, Jr., Juan F. Macias-Velasco, Ting Wang
{"title":"Charting the regulatory landscape of TP53 on transposable elements in cancer","authors":"Xuan Qu, Yonghao Liang, Colin McCornack, Xiaoyun Xing, Heather Schmidt, Chad Tomlinson, Catrina Fronick, Edward A. Belter, Jr., Juan F. Macias-Velasco, Ting Wang","doi":"10.1101/gr.279398.124","DOIUrl":"https://doi.org/10.1101/gr.279398.124","url":null,"abstract":"The relationship between TP53 and transposable elements (TEs) has been obscure. Given the important role of TEs in oncogenesis, a comprehensive profiling of TE expression dynamics under the regulation of TP53 provides valuable resources for more clarity in TP53's roles in cancer. In this study, we characterized the TE transcriptomic landscape using long-read RNA-seq and short-read RNA-seq in three cancer cell lines varying only in <em>TP53</em> genetic status. To identify transcripts that use TEs as potential promoters, we developed a computational pipeline, TEProf3, and identified in total 1942 transcripts with high confidence. Among these TE-derived transcripts, 239 are activated by TP53 and 221 are repressed by TP53. These TP53-responsive TE-derived transcripts are mainly driven by members of the ERV and LINE families. Following knockdown of wild-type (WT) TP53 expression, rescuing WT TP53 expression allows for partial recovery of the TE expression profile observed in the context of chronic TP53 expression. TP53 mutations R175H and R273H manifest their oncogenic characteristic partially through activating TE promoters in a cell type–specific manner. Lastly, we identified important sequence motifs that help govern the interactions between TEs and TP53, where TP53 activates TEs with TP53 binding motifs through direct binding and represses TEs indirectly via other pathways. Overall, we present a comprehensive profiling of the impact of TP53 on the activity of TE-derived promoters in isogenic cancer cell lines and provide a high-confidence TE expression atlas of TE promoters that are direct and indirect targets of TP53.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"3 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Genome researchPub Date : 2025-05-13DOI: 10.1101/gr.280305.124
Maria Grazia Mendoza-Ferri, Gwendoline Lozachmeur, Maximilien Duvina, Laetitia Perret, Didier Merciris, Anne Gigout, Marco Antonio Mendoza-Parra
{"title":"Tissular chromatin states cartography based on double-barcoded DNA arrays capturing unloaded PA-Tn5 Transposase","authors":"Maria Grazia Mendoza-Ferri, Gwendoline Lozachmeur, Maximilien Duvina, Laetitia Perret, Didier Merciris, Anne Gigout, Marco Antonio Mendoza-Parra","doi":"10.1101/gr.280305.124","DOIUrl":"https://doi.org/10.1101/gr.280305.124","url":null,"abstract":"Recent developments in spatial omics are revoluzionating our understanding of tissue structures organization and their deregulation in disease. Here, we present a strategy for capturing chromatin histone modification signatures across tissue sections by taking advantage of a double-barcoded DNA arrays design compatible with in situ protein A-Transposase Tn5 tagmentation. This approach has been validated in presence of fresh-frozen mouse brain tissues but also in decalcified formalin-fixed paraffin-embedded (FFPE) mouse paws samples, where either the histone modification H3K4 tri-methylation or H3K27-acethylation has been used as proxy for interrogating active promoter signatures. Furthermore, since combinatorial enrichment of multiple histone modifications were shown to code for various states of gene transcriptional status (active, bivalent, repressed), we have integrated several histone modifications issued from consecutive mouse embryos to reveal changes in chromatin states across the tissue. Overall, this spatial epigenomics technology combined with the use of a spatial chromatin states analytical strategy paves the way for future epigenetics studies for addressing tissue architecture complexity.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"4 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143946067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"STCC enhances spatial domain detection through consensus clustering of spatial transcriptomics data","authors":"Congcong Hu, Nana Wei, Jiyuan Yang, Hua-Jun Wu, Xiaoqi Zheng","doi":"10.1101/gr.280031.124","DOIUrl":"https://doi.org/10.1101/gr.280031.124","url":null,"abstract":"The rapid advance of spatially resolved transcriptomics technologies has yielded substantial spatial transcriptomics data. Deriving biological insights from these data poses nontrivial computational and analysis challenges, of which the most fundamental step is spatial domain detection (or spatial clustering). Although a number of tools for spatial domain detection have been proposed in recent years, their performance varies across data sets and experimental platforms. It is thus an important task to take full advantage of different tools to get a more accurate and stable result through consensus strategy. In this work, we developed STCC, a novel consensus clustering framework for spatial transcriptomics data that aggregates outcomes from state-of-the-art tools using a variety of consensus strategies, including Onehot-based, average-based, hypergraph-based, and wNMF-based methods. Comprehensive assessments on simulated and real data from distinct experimental platforms show that consensus clustering significantly improves clustering accuracy over individual methods under varied input parameters. For normal tissue samples exhibiting clear layered structure, consensus clustering by integrating multiple baseline methods leads to improved results. Conversely, when analyzing tumor samples that display scattered cell type distribution patterns, integration of a single baseline method yields satisfactory performance. For consensus strategies, average-based and hypergraph-based approaches demonstrate optimal precision and stability. Overall, STCC provides a scalable and practical solution for spatial domain detection in spatial transcriptomics data, laying a solid foundation for future research and applications in spatial transcriptomics.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"25 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}