{"title":"Contribution of germline and somatic mutations to risk of neuromyelitis optica spectrum disorder.","authors":"Tomohiro Yata, Go Sato, Kotaro Ogawa, Tatsuhiko Naito, Kyuto Sonehara, Ryunosuke Saiki, Ryuya Edahiro, Shinichi Namba, Mitsuru Watanabe, Yuya Shirai, Kenichi Yamamoto, Ho NamKoong, Tomoko Nakanishi, Yuji Yamamoto, Akiko Hosokawa, Mamoru Yamamoto, Eri Oguro-Igashira, Takuro Nii, Yuichi Maeda, Kimiko Nakajima, Rika Nishikawa, Hiroaki Tanaka, Shingo Nakayamada, Koichi Matsuda, Chikako Nishigori, Shigetoshi Sano, Makoto Kinoshita, Ryuji Koike, Akinori Kimura, Seiya Imoto, Satoru Miyano, Koichi Fukunaga, Masahito Mihara, Yuko Shimizu, Izumi Kawachi, Katsuichi Miyamoto, Yoshiya Tanaka, Atsushi Kumanogoh, Masaaki Niino, Yuji Nakatsuji, Seishi Ogawa, Takuya Matsushita, Jun-Ichi Kira, Hideki Mochizuki, Noriko Isobe, Tatsusada Okuno, Yukinori Okada","doi":"10.1016/j.xgen.2025.100776","DOIUrl":"10.1016/j.xgen.2025.100776","url":null,"abstract":"<p><p>Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease characterized by optic neuritis and transverse myelitis, with an unclear genetic background. A genome-wide meta-analysis of NMOSD in Japanese individuals (240 patients and 50,578 controls) identified significant associations with the major histocompatibility complex region and a common variant close to CCR6 (rs12193698; p = 1.8 × 10<sup>-8</sup>, odds ratio [OR] = 1.73). In single-cell RNA sequencing (scRNA-seq) analysis (25 patients and 101 controls), the CCR6 risk variant showed disease-specific expression quantitative trait loci effects in CD4<sup>+</sup> T (CD4T) cell subsets. Furthermore, we detected somatic mosaic chromosomal alterations (mCAs) in various autoimmune diseases and found that mCAs increase the risk of NMOSD (OR = 3.37 for copy number alteration). In scRNA-seq data, CD4T cells with 21q loss, a recurrently observed somatic event in NMOSD, showed dysregulation of type I interferon-related genes. Our integrated study identified novel germline and somatic mutations associated with NMOSD pathogenesis.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100776"},"PeriodicalIF":11.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell genomicsPub Date : 2025-03-12Epub Date: 2025-02-21DOI: 10.1016/j.xgen.2025.100774
Jiyun Zhou, Chongyuan Luo, Hanqing Liu, Matthew G Heffel, Richard E Straub, Joel E Kleinman, Thomas M Hyde, Joseph R Ecker, Daniel R Weinberger, Shizhong Han
{"title":"Deep learning imputes DNA methylation states in single cells and enhances the detection of epigenetic alterations in schizophrenia.","authors":"Jiyun Zhou, Chongyuan Luo, Hanqing Liu, Matthew G Heffel, Richard E Straub, Joel E Kleinman, Thomas M Hyde, Joseph R Ecker, Daniel R Weinberger, Shizhong Han","doi":"10.1016/j.xgen.2025.100774","DOIUrl":"10.1016/j.xgen.2025.100774","url":null,"abstract":"<p><p>DNA methylation (DNAm) is a key epigenetic mark with essential roles in gene regulation, mammalian development, and human diseases. Single-cell technologies enable profiling DNAm at cytosines in individual cells, but they often suffer from low coverage for CpG sites. We introduce scMeFormer, a transformer-based deep learning model for imputing DNAm states at each CpG site in single cells. Comprehensive evaluations across five single-nucleus DNAm datasets from human and mouse demonstrate scMeFormer's superior performance over alternative models, achieving high-fidelity imputation even with coverage reduced to 10% of original CpG sites. Applying scMeFormer to a single-nucleus DNAm dataset from the prefrontal cortex of patients with schizophrenia and controls identified thousands of schizophrenia-associated differentially methylated regions that would have remained undetectable without imputation and added granularity to our understanding of epigenetic alterations in schizophrenia. We anticipate that scMeFormer will be a valuable tool for advancing single-cell DNAm studies.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100774"},"PeriodicalIF":11.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell genomicsPub Date : 2025-03-12DOI: 10.1016/j.xgen.2025.100808
Gabrielle A Hartley, Mariam Okhovat, Savannah J Hoyt, Emily Fuller, Nicole Pauloski, Nicolas Alexandre, Ivan Alexandrov, Ryan Drennan, Danilo Dubocanin, David M Gilbert, Yizi Mao, Christine McCann, Shane Neph, Fedor Ryabov, Takayo Sasaki, Jessica M Storer, Derek Svendsen, William Troy, Jackson Wells, Leighton Core, Andrew Stergachis, Lucia Carbone, Rachel J O'Neill
{"title":"Centromeric transposable elements and epigenetic status drive karyotypic variation in the eastern hoolock gibbon.","authors":"Gabrielle A Hartley, Mariam Okhovat, Savannah J Hoyt, Emily Fuller, Nicole Pauloski, Nicolas Alexandre, Ivan Alexandrov, Ryan Drennan, Danilo Dubocanin, David M Gilbert, Yizi Mao, Christine McCann, Shane Neph, Fedor Ryabov, Takayo Sasaki, Jessica M Storer, Derek Svendsen, William Troy, Jackson Wells, Leighton Core, Andrew Stergachis, Lucia Carbone, Rachel J O'Neill","doi":"10.1016/j.xgen.2025.100808","DOIUrl":"10.1016/j.xgen.2025.100808","url":null,"abstract":"<p><p>Great apes have maintained a stable karyotype with few large-scale rearrangements; in contrast, gibbons have undergone a high rate of chromosomal rearrangements coincident with rapid centromere turnover. Here, we characterize fully assembled centromeres in the eastern hoolock gibbon, Hoolock leuconedys (HLE), finding a diverse group of transposable elements (TEs) that differ from the canonical alpha-satellites found across centromeres of other apes. We find that HLE centromeres contain a CpG methylation centromere dip region, providing evidence that this epigenetic feature is conserved in the absence of satellite arrays. We uncovered a variety of atypical centromeric features, including protein-coding genes and mismatched replication timing. Further, we identify duplications and deletions in HLE centromeres that distinguish them from other gibbons. Finally, we observed differentially methylated TEs, topologically associated domain boundaries, and segmental duplications at chromosomal breakpoints, and thus propose that a combination of multiple genomic attributes with propensities for chromosome instability shaped gibbon centromere evolution.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100808"},"PeriodicalIF":11.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell genomicsPub Date : 2025-03-12DOI: 10.1016/j.xgen.2025.100809
Sool Lee, Hakhamanesh Mostafavi
{"title":"Missing regulatory effects on complex traits: Contribution of distal variants.","authors":"Sool Lee, Hakhamanesh Mostafavi","doi":"10.1016/j.xgen.2025.100809","DOIUrl":"10.1016/j.xgen.2025.100809","url":null,"abstract":"<p><p>Most genetic effects on complex traits lie in non-coding regions, yet many show no regulatory activity in standard gene expression assays. In this issue of Cell Genomics, Arthur et al.<sup>1</sup> add early development-like cell types and chromatin assays, showing that distal variants missed in expression assays partly explain this discrepancy.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":"5 3","pages":"100809"},"PeriodicalIF":11.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell genomicsPub Date : 2025-03-12Epub Date: 2025-02-27DOI: 10.1016/j.xgen.2025.100780
Sahin Naqvi, Seungsoo Kim, Saman Tabatabaee, Anusri Pampari, Anshul Kundaje, Jonathan K Pritchard, Joanna Wysocka
{"title":"Transfer learning reveals sequence determinants of the quantitative response to transcription factor dosage.","authors":"Sahin Naqvi, Seungsoo Kim, Saman Tabatabaee, Anusri Pampari, Anshul Kundaje, Jonathan K Pritchard, Joanna Wysocka","doi":"10.1016/j.xgen.2025.100780","DOIUrl":"10.1016/j.xgen.2025.100780","url":null,"abstract":"<p><p>Deep learning models have advanced our ability to predict cell-type-specific chromatin patterns from transcription factor (TF) binding motifs, but their application to perturbed contexts remains limited. We applied transfer learning to predict how concentrations of the dosage-sensitive TFs TWIST1 and SOX9 affect regulatory element (RE) chromatin accessibility in facial progenitor cells, achieving near-experimental accuracy. High-affinity motifs that allow for heterotypic TF co-binding and are concentrated at the center of REs buffer against quantitative changes in TF dosage and predict unperturbed accessibility. Conversely, low-affinity or homotypic binding motifs distributed throughout REs drive sensitive responses with minimal impact on unperturbed accessibility. Both buffering and sensitizing features display purifying selection signatures. We validated these sequence features through reporter assays and demonstrated that TF-nucleosome competition can explain low-affinity motifs' sensitizing effects. This combination of transfer learning and quantitative chromatin response measurements provides a novel approach for uncovering additional layers of the cis-regulatory code.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100780"},"PeriodicalIF":11.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A highland-adaptation variant near MCUR1 reduces its transcription and attenuates erythrogenesis in Tibetans.","authors":"Jie Ping, Xinyi Liu, Yiming Lu, Cheng Quan, Pengcheng Fan, Hao Lu, Qi Li, Cuiling Wang, Zheng Zhang, Mengyu Liu, Shunqi Chen, Lingle Chang, Yuqing Jiang, Qilin Huang, Jie Liu, Tana Wuren, Huifang Liu, Ying Hao, Longli Kang, Guanjun Liu, Hui Lu, Xiaojun Wei, Yuting Wang, Yuanfeng Li, Hao Guo, Yongquan Cui, Haoxiang Zhang, Yang Zhang, Yujia Zhai, Yaoxi He, Wangshan Zheng, Xuebin Qi, Ouzhuluobu, Huiping Ma, Linpeng Yang, Xin Wang, Wanjun Jin, Ying Cui, Rili Ge, Shizheng Wu, Yuan Wei, Bing Su, Fuchu He, Hongxing Zhang, Gangqiao Zhou","doi":"10.1016/j.xgen.2025.100782","DOIUrl":"10.1016/j.xgen.2025.100782","url":null,"abstract":"<p><p>To identify genomic regions subject to positive selection that might contain genes involved in high-altitude adaptation (HAA), we performed a genome-wide scan by whole-genome sequencing of Tibetan highlanders and Han lowlanders. We revealed a collection of candidate genes located in 30 genomic loci under positive selection. Among them, MCUR1 at 6p23 was a novel pronounced candidate. By single-cell RNA sequencing and comprehensive functional studies, we demonstrated that MCUR1 depletion leads to impairment of erythropoiesis under hypoxia and normoxia. Mechanistically, MCUR1 knockdown reduced mitochondrial Ca<sup>2+</sup> uptake and then concomitantly increased cytosolic Ca<sup>2+</sup> levels, which thereby reduced erythropoiesis via the CAMKK2-AMPK-mTOR axis. Further, we revealed rs61644582 at 6p23 as an expression quantitative trait locus for MCUR1 and a functional variant that confers an allele-specific transcriptional regulation of MCUR1. Overall, MCUR1-mediated mitochondrial Ca<sup>2+</sup> homeostasis is highlighted as a novel regulator of erythropoiesis, deepening our understanding of the genetic mechanism of HAA.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100782"},"PeriodicalIF":11.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell genomicsPub Date : 2025-03-12Epub Date: 2025-03-04DOI: 10.1016/j.xgen.2025.100784
Hung-Hsin Chen, Heather M Highland, Elizabeth G Frankel, Alyssa C Scartozzi, Xinruo Zhang, Rashedeh Roshani, Priya Sharma, Asha Kar, Victoria L Buchanan, Hannah G Polikowsky, Lauren E Petty, Jungkyun Seo, Mohammad Yaser Anwar, Daeeun Kim, Mariaelisa Graff, Kristin L Young, Wanying Zhu, Kalypso Karastergiou, Douglas M Shaw, Anne E Justice, Lindsay Fernández-Rhodes, Mohanraj Krishnan, Absalon Gutierrez, Peter J McCormick, Carlos A Aguilar-Salinas, Maria Teresa Tusié-Luna, Linda Liliana Muñoz-Hernandez, Miguel Herrera-Hernandez, Miryoung Lee, Eric R Gamazon, Nancy J Cox, Päivi Pajukanta, Susan K Fried, Penny Gordon-Larsen, Ravi V Shah, Susan P Fisher-Hoch, Joseph B McCormick, Kari E North, Jennifer E Below
{"title":"Multiomics reveal key inflammatory drivers of severe obesity: IL4R, LILRA5, and OSM.","authors":"Hung-Hsin Chen, Heather M Highland, Elizabeth G Frankel, Alyssa C Scartozzi, Xinruo Zhang, Rashedeh Roshani, Priya Sharma, Asha Kar, Victoria L Buchanan, Hannah G Polikowsky, Lauren E Petty, Jungkyun Seo, Mohammad Yaser Anwar, Daeeun Kim, Mariaelisa Graff, Kristin L Young, Wanying Zhu, Kalypso Karastergiou, Douglas M Shaw, Anne E Justice, Lindsay Fernández-Rhodes, Mohanraj Krishnan, Absalon Gutierrez, Peter J McCormick, Carlos A Aguilar-Salinas, Maria Teresa Tusié-Luna, Linda Liliana Muñoz-Hernandez, Miguel Herrera-Hernandez, Miryoung Lee, Eric R Gamazon, Nancy J Cox, Päivi Pajukanta, Susan K Fried, Penny Gordon-Larsen, Ravi V Shah, Susan P Fisher-Hoch, Joseph B McCormick, Kari E North, Jennifer E Below","doi":"10.1016/j.xgen.2025.100784","DOIUrl":"10.1016/j.xgen.2025.100784","url":null,"abstract":"<p><p>Polygenic severe obesity (body mass index [BMI] ≥40 kg/m<sup>2</sup>) has increased, especially in Hispanic/Latino populations, yet we know little about the underlying mechanistic pathways. We analyzed whole-blood multiomics data to identify genes differentially regulated in severe obesity in Mexican Americans from the Cameron County Hispanic Cohort. Our RNA sequencing analysis identified 124 genes significantly differentially expressed between severe obesity cases (BMI ≥40 kg/m<sup>2</sup>) and controls (BMI <25 kg/m<sup>2</sup>); 33% replicated in an independent sample from the same population. Our integrative approach identified inflammatory genes, including IL4R, ZNF438, and LILRA5. Several genes displayed transcriptomic effects on severe obesity in subcutaneous adipose tissue. We further showed that the genetic regulation of these genes is associated with several traits in a large biobank, including bone fractures, obstructive sleep apnea, and hyperaldosteronism, illuminating potential risk mechanisms. Our findings furnish a molecular architecture of the severe obesity phenotype across multiple molecular domains.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100784"},"PeriodicalIF":11.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell genomicsPub Date : 2025-03-12DOI: 10.1016/j.xgen.2025.100817
Masahiro Nagano, Anders S Hansen
{"title":"Distance matters: How protein regulators facilitate enhancer-promoter interactions and transcription.","authors":"Masahiro Nagano, Anders S Hansen","doi":"10.1016/j.xgen.2025.100817","DOIUrl":"10.1016/j.xgen.2025.100817","url":null,"abstract":"<p><p>Cohesin, transcription factors (TFs), and mediator complex components regulate gene expression partly by regulating enhancer-promoter (E-P) communication. A new study combined E-P distance-controlled reporter screens with the inhibition or degradation of regulatory proteins and uncovered a distance-dependent effect across cohesin, TFs, and mediator complex components.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":"5 3","pages":"100817"},"PeriodicalIF":11.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell genomicsPub Date : 2025-03-12Epub Date: 2025-02-25DOI: 10.1016/j.xgen.2025.100778
Sjoerd J D Tjalsma, Niels J Rinzema, Marjon J A M Verstegen, Michelle J Robers, Andrea Nieto-Aliseda, Richard A Gremmen, Amin Allahyar, Mauro J Muraro, Peter H L Krijger, Wouter de Laat
{"title":"Long-range enhancer-controlled genes are hypersensitive to regulatory factor perturbations.","authors":"Sjoerd J D Tjalsma, Niels J Rinzema, Marjon J A M Verstegen, Michelle J Robers, Andrea Nieto-Aliseda, Richard A Gremmen, Amin Allahyar, Mauro J Muraro, Peter H L Krijger, Wouter de Laat","doi":"10.1016/j.xgen.2025.100778","DOIUrl":"10.1016/j.xgen.2025.100778","url":null,"abstract":"<p><p>Cell-type-specific gene activation is regulated by enhancers, sometimes located at large genomic distances from target gene promoters. Whether distal enhancers require specific factors to orchestrate gene regulation remains unclear. Here, we used enhancer distance-controlled reporter screens to find candidate factors. We depleted them and employed activity-by-contact predictions to genome-wide classify genes based on enhancer distance. Predicted distal enhancers typically control tissue-restricted genes and often are strong enhancers. We find cohesin, but also mediator, most specifically required for long-range activation, with cohesin repressing short-range gene activation and prioritizing distal over proximal HBB genes competing for shared enhancers. Long-range controlled genes are also most sensitive to perturbations of other regulatory proteins and to BET inhibitor JQ1, this being more a consequence of their distinct enhancer features than distance. Our work predicts that lengthening of intervening sequences can help limit the expression of target genes to specialized cells with optimal trans-factor environments.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100778"},"PeriodicalIF":11.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell genomicsPub Date : 2025-03-12Epub Date: 2025-03-05DOI: 10.1016/j.xgen.2025.100806
Mengjie Chen
{"title":"Capturing cell-type-specific activities of cis-regulatory elements from peak-based single-cell ATAC-seq.","authors":"Mengjie Chen","doi":"10.1016/j.xgen.2025.100806","DOIUrl":"10.1016/j.xgen.2025.100806","url":null,"abstract":"<p><p>Single-cell ATAC sequencing (scATAC-seq), a state-of-the-art genomic technique designed to map chromatin accessibility at the single-cell level, presents unique analytical challenges due to limited sampling and data sparsity. In this study, we use case studies to highlight the limitations of conventional peak-based methods for processing scATAC-seq data. These methods can fail to capture precise cell-type-specific regulatory signals, producing results that are difficult to interpret and lack portability, thereby compromising the reproducibility of research findings. To overcome these issues, we introduce CREscendo, a method that utilizes Tn5 cleavage frequencies and regulatory annotations to identify differential usage of candidate regulatory elements (CREs) across cell types. Our research advocates for moving away from traditional peak-based quantification in scATAC-seq toward a more robust framework that relies on a standardized reference of annotated CREs, enhancing both the accuracy and reproducibility of genomic studies.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100806"},"PeriodicalIF":11.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
