Genome research最新文献_第6页

Genetic variation in recalcitrant repetitive regions of the Drosophila melanogaster genome 果蝇基因组中顽固性重复区域的遗传变异

IF 7 2区生物学

Genome research Pub Date : 2025-07-16 DOI: 10.1101/gr.280728.125

Harsh G. Shukla, Mahul Chakraborty, J.J. Emerson

{"title":"Genetic variation in recalcitrant repetitive regions of the Drosophila melanogaster genome","authors":"Harsh G. Shukla, Mahul Chakraborty, J.J. Emerson","doi":"10.1101/gr.280728.125","DOIUrl":"https://doi.org/10.1101/gr.280728.125","url":null,"abstract":"Many essential functions of organisms are encoded in highly repetitive genomic regions, including histones involved in DNA packaging, centromeres that are core components of chromosome segregation, ribosomal RNA comprising the protein translation machinery, telomeres that ensure chromosome integrity, piRNA clusters encoding host defenses against selfish elements, and virtually the entire Y Chromosome. These regions, formed by highly similar tandem arrays, pose significant challenges for experimental and computational studies, impeding sequence-level descriptions essential for understanding genetic variation. Here, we report the assembly and variation analysis of such repetitive regions in Drosophila melanogaster, offering significant improvements to the existing community reference assembly. Our work successfully recovers previously elusive segments, including complete reconstructions of the histone locus and the pericentric heterochromatin of the X Chromosome, spanning the Stellate locus to the distal flank of the rDNA cluster. To infer structural changes in these regions where alignments are often not practicable, we introduce landmark anchors based on unique variants that are putatively orthologous. These regions display considerable structural variation between different D. melanogaster strains, exhibiting differences in copy number and organization of homologous repeat units between haplotypes. In the histone cluster, although we observe minimal genetic exchange indicative of meiotic crossing over, the variation patterns suggest mechanisms such as unequal sister chromatid exchange. We also examine the prevalence and scale of concerted evolution in the histone and Stellate clusters and discuss the mechanisms underlying these observed patterns.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"94 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639724","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}

引用次数: 0

Alternative splicing generates HER2 isoform diversity underlying antibody-drug conjugate resistance in breast cancer 选择性剪接产生HER2亚型多样性是乳腺癌抗体-药物偶联耐药的基础

IF 7 2区生物学

Genome research Pub Date : 2025-07-15 DOI: 10.1101/gr.280304.124

Gabriela D. A. Guardia, Carlos H dos Anjos, Aline Rangel-Pozzo, Filipe F dos Santos, Alexander Birbrair, Paula F Asprino, Anamaria A Camargo, Pedro A F Galante

{"title":"Alternative splicing generates HER2 isoform diversity underlying antibody-drug conjugate resistance in breast cancer","authors":"Gabriela D. A. Guardia, Carlos H dos Anjos, Aline Rangel-Pozzo, Filipe F dos Santos, Alexander Birbrair, Paula F Asprino, Anamaria A Camargo, Pedro A F Galante","doi":"10.1101/gr.280304.124","DOIUrl":"https://doi.org/10.1101/gr.280304.124","url":null,"abstract":"Breast cancer (BC) is a heterogeneous disease that can be molecularly classified based on the expression of the ERBB2 receptor (also known as HER2) and hormone receptors. Targeted therapies for HER2-positive BC, such as trastuzumab, antibody-drug conjugates (ADCs) and tyrosine kinase inhibitors, have improved patient outcomes but primary/acquired resistance still pose challenges that can limit treatments' long-term efficacy. Addressing these obstacles is vital for enhancing therapeutic strategies and patient care. Alternative splicing, a post-transcriptional mechanism that enhances transcript diversity (isoforms), can produce proteins with varied functions, cellular localizations, or binding properties. Here, we comprehensively characterized the HER2 alternative splicing isoforms, assessed their expression in primary BC patients and cell lines, and explored their role in resistance to anti-HER2 therapies. We expanded the catalog of known HER2 protein-coding isoforms from 13 to 90, revealing distinct patterns of protein domains, cellular localizations, and protein structures, along with their antibody-binding sites. By profiling expression in 561 primary BC samples and mass spectrometry data, we discovered a complex landscape of HER2 isoform, revealing novel transcripts that were previously unrecognized and are not assessed in routine clinical practice. Finally, the assessment of HER2 isoform expression in BC cell cultures sensitive or resistant to trastuzumab and ADCs revealed that drug-resistant cells shifted their expression toward isoforms lacking antibody-binding domains. Our results broaden the understanding of HER2 isoforms, revealing distinct mechanisms of potential resistance to anti-HER2 therapies, particularly ADCs. This expanded landscape of HER2 isoforms emphasizes the crucial role of alternative splicing investigations in advancing precision-targeted cancer therapies.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"95 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639723","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}

引用次数: 0

A high-throughput screening method for selecting feature SNPs to evaluate breed diversity and infer ancestry 一种高通量筛选特征snp的方法来评估品种多样性和推断祖先

IF 7 2区生物学

Genome research Pub Date : 2025-07-15 DOI: 10.1101/gr.280176.124

Meilin Zhang, Heng Du, Yu Zhang, Yue Zhuo, Zhen Liu, Yahui Xue, Lei Zhou, Sixuan Zhou, Wanying Li, Jian-Feng Liu

{"title":"A high-throughput screening method for selecting feature SNPs to evaluate breed diversity and infer ancestry","authors":"Meilin Zhang, Heng Du, Yu Zhang, Yue Zhuo, Zhen Liu, Yahui Xue, Lei Zhou, Sixuan Zhou, Wanying Li, Jian-Feng Liu","doi":"10.1101/gr.280176.124","DOIUrl":"https://doi.org/10.1101/gr.280176.124","url":null,"abstract":"As the scale of deep whole-genome sequencing (WGS) data has grown exponentially, hundreds of millions of single nucleotide polymorphisms (SNPs) have been identified in livestock. Utilizing these massive SNP data in population stratification analysis, ancestry prediction, and breed diversity assessments leads to overfitting issues in computational models and creates computational bottlenecks. Therefore, selecting genetic variants that express high amounts of information for use in population diversity studies and ancestry inference becomes critically important. Here, we develop a method, HITSNP, that combines feature selection and machine learning algorithms to select high-representative SNPs that can effectively estimate breed diversity and infer ancestry. HITSNP outperforms existing feature selection methods in estimating accuracy and computational stability. Furthermore, HITSNP offers a new algorithm to predict the number and composition of ancestral populations using a small number of SNPs, and avoiding calculating the number of clusters. Taken together, HITSNP facilitates the research of population structure, animal breeding, and animal resource protection.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"109 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639721","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}

引用次数: 0

CGC1, a new reference genome for Caenorhabditis elegans 秀丽隐杆线虫新的参考基因组CGC1

IF 7 2区生物学

Genome research Pub Date : 2025-07-15 DOI: 10.1101/gr.280274.124

Kazuki Ichikawa, Massa J. Shoura, Karen L. Artiles, Dae-Eun Jeong, Chie Owa, Haruka Kobayashi, Yoshihiko Suzuki, Manami Kanamori, Yu Toyoshima, Yuichi Iino, Ann E. Rougvie, Lamia Wahba, Andrew Z. Fire, Erich M. Schwarz, Shinichi Morishita

{"title":"CGC1, a new reference genome for Caenorhabditis elegans","authors":"Kazuki Ichikawa, Massa J. Shoura, Karen L. Artiles, Dae-Eun Jeong, Chie Owa, Haruka Kobayashi, Yoshihiko Suzuki, Manami Kanamori, Yu Toyoshima, Yuichi Iino, Ann E. Rougvie, Lamia Wahba, Andrew Z. Fire, Erich M. Schwarz, Shinichi Morishita","doi":"10.1101/gr.280274.124","DOIUrl":"https://doi.org/10.1101/gr.280274.124","url":null,"abstract":"The original 100.3 Mb reference genome for Caenorhabditis elegans, generated from the wild-type laboratory strain N2, has been crucial for analysis of C. elegans since 1998 and has been considered complete since 2005. Unexpectedly, this long-standing reference was shown to be incomplete in 2019 by a genome assembly from the N2-derived strain VC2010. Moreover, genetically divergent versions of N2 have arisen over decades of research and hindered reproducibility of C. elegans genetics and genomics. Here we provide a 106.4 Mb gap-free, telomere-to-telomere genome assembly of C. elegans, generated from CGC1, an isogenic derivative of the N2 strain. We use improved long-read sequencing and manual assembly of 43 recalcitrant genomic regions to overcome deficiencies of prior N2 and VC2010 assemblies and to assemble tandem repeat loci, including a 772 kb sequence for the 45S rRNA genes. Although many differences from earlier assemblies come from repeat regions, unique additions to the genome are also found. Of 19,972 protein-coding genes in the N2 assembly, 19,790 (99.1%) encode products that are unchanged in the CGC1 assembly. The CGC1 assembly also may encode 183 new protein-coding and 163 new ncRNA genes. CGC1 thus provides both a completely defined reference genome and corresponding isogenic wild-type strain for C. elegans, allowing unique opportunities for model and systems biology.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"1 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629691","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}

引用次数: 0

A novel multislice framework for precision 3D spatial domain reconstruction and disease pathology analysis 一种用于精确三维空间域重建和疾病病理分析的新型多层框架

IF 7 2区生物学

Genome research Pub Date : 2025-07-14 DOI: 10.1101/gr.280281.124

Daijun Zhang, Ren Qi, Xun Lan, Bin Liu

{"title":"A novel multislice framework for precision 3D spatial domain reconstruction and disease pathology analysis","authors":"Daijun Zhang, Ren Qi, Xun Lan, Bin Liu","doi":"10.1101/gr.280281.124","DOIUrl":"https://doi.org/10.1101/gr.280281.124","url":null,"abstract":"The development of spatial transcriptomics (ST) technologies has revolutionized the way we map the complex organization and functions of tissues. These technologies offer valuable insights into the organization and function of complex biological systems. However, existing methods often focus too narrowly on single modalities or resolutions, thereby hindering the comprehensive capture of multilayered biological heterogeneity. Here, STMSC is proposed as a multislice joint analysis framework featuring a precorrection mechanism that enables the precise identification of complex spatial domains, advancing disease pathology insights. STMSC assumes that precise three-dimensional (3D) reconstruction is essential for an in-depth investigation of tissue components and mechanisms. Incorporating hematoxylin and eosin (H&E) imaging data, STMSC enhances slice alignment accuracy in 3D reconstruction. By deconstructing microenvironments, it reconstructs fine-grained cellular landscapes and emphasizes collective cellular behavior in defining spatial domains. Its graph attention autoencoder with precorrection balances biological information at different levels, improving the accuracy of ST analyses. By analyzing consecutive tissue slices and pathological data sets, STMSC accurately reconstructs 3D structures and provides deeper insights into complex cancer environments. Specifically, STMSC captures intra- and interstage heterogeneity in cancer development, offering novel insights into the complexity of pathological tissue structures.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"51 1 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622370","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}

引用次数: 0

Uncovering methylation-dependent genetic effects on regulatory element function in diverse genomes 揭示甲基化依赖性基因对不同基因组调控元件功能的影响

IF 7 2区生物学

Genome research Pub Date : 2025-07-14 DOI: 10.1101/gr.279957.124

Rachel M. Petersen, Christopher M. Vockley, Amanda J. Lea

{"title":"Uncovering methylation-dependent genetic effects on regulatory element function in diverse genomes","authors":"Rachel M. Petersen, Christopher M. Vockley, Amanda J. Lea","doi":"10.1101/gr.279957.124","DOIUrl":"https://doi.org/10.1101/gr.279957.124","url":null,"abstract":"A major goal in evolutionary biology and biomedicine is to understand the complex interactions between genetic variants, the epigenome, and gene expression. However, the causal relationships between these factors remain poorly understood. mSTARR-seq, a methylation-sensitive massively parallel reporter assay, is capable of identifying methylation-dependent regulatory activity at many thousands of genomic regions simultaneously and allows for the testing of causal relationships between DNA methylation and gene expression on a region-by-region basis. Here, we develop a multiplexed mSTARR-seq protocol to assay naturally occurring human genetic variation from 25 individuals from 10 localities in Europe and Africa. We identify 6957 regulatory elements in either the unmethylated or methylated state, and this set was enriched for enhancer and promoter chromatin annotations, as expected. The expression of 58% of these regulatory elements is modulated by methylation, which is generally associated with decreased transcription. Within our set of regulatory elements, we use allele-specific expression analyses to identify 8020 sites with genetic effects on gene regulation; further, we find that 42.3% of these genetic effects vary in direction or magnitude between methylated and unmethylated states. Sites exhibiting methylation-dependent genetic effects are enriched for GWAS and EWAS annotations, implicating them in human disease. Compared with data sets that assay DNA from a single European ancestry individual, our multiplexed assay is able to uncover more genetic effects and methylation-dependent genetic effects, highlighting the importance of including diverse genomes in assays that aim to understand gene regulatory processes.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"45 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622378","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}

引用次数: 0

A map of enhancer regions in primary human neural progenitor cells using capture STARR-seq 利用捕获的STARR-seq技术绘制人类原代神经祖细胞的增强子区域图

IF 7 2区生物学

Genome research Pub Date : 2025-07-11 DOI: 10.1101/gr.279584.124

Sophia C. Gaynor-Gillett, Lijun Cheng, Manman Shi, Jason Liu, Gaoyuan Wang, Megan Spector, Qiuyu Guo, Le Qi, Mary Flaherty, Martha Wall, Ahyeon Hwang, Mengting Gu, Zhanlin Chen, Yuhang Chen, PsychENCODE Consortium, Jennifer R. Moran, Jing Zhang, Donghoon Lee, Mark Gerstein, Daniel Geschwind, Kevin P. White

{"title":"A map of enhancer regions in primary human neural progenitor cells using capture STARR-seq","authors":"Sophia C. Gaynor-Gillett, Lijun Cheng, Manman Shi, Jason Liu, Gaoyuan Wang, Megan Spector, Qiuyu Guo, Le Qi, Mary Flaherty, Martha Wall, Ahyeon Hwang, Mengting Gu, Zhanlin Chen, Yuhang Chen, PsychENCODE Consortium, Jennifer R. Moran, Jing Zhang, Donghoon Lee, Mark Gerstein, Daniel Geschwind, Kevin P. White","doi":"10.1101/gr.279584.124","DOIUrl":"https://doi.org/10.1101/gr.279584.124","url":null,"abstract":"Genome-wide association studies (GWASs) and expression analyses implicate noncoding regulatory regions as harboring risk factors for psychiatric disease, but functional characterization of these regions remains limited. Here, we perform capture STARR-sequencing of over 70,000 candidate regions to identify active enhancers in primary human neural progenitor cells (phNPCs). We select candidate regions by integrating data from NPCs, prefrontal cortex, developmental timepoints, and GWASs. Over 8000 regions demonstrate enhancer activity in the phNPCs, and we link these regions to over 2200 predicted target genes. These genes are involved in neuronal and psychiatric disease-associated pathways, including neuronal system, nervous system development, and developmental delay. We functionally validate a subset of these enhancers using mutation STARR-sequencing and CRISPR deletions, demonstrating the effects of genetic variation on enhancer activity and enhancer deletion on gene expression. Overall, we identify thousands of highly active enhancers and functionally validated a subset of these enhancers, improving our understanding of regulatory networks underlying brain function and disease.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"12 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144611024","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}

引用次数: 0

De novo gene birth and the conundrum of ORFan genes in bacteria 细菌中新生基因的诞生和ORFan基因的难题

IF 7 2区生物学

Genome research Pub Date : 2025-07-10 DOI: 10.1101/gr.280157.124

Md. Hassan uz-Zaman, Howard Ochman

引用次数: 0

Lambdoid phages with abundant Chi recombination hotspots reflect diverse viral strategies for recombination-dependent growth 具有丰富Chi重组热点的羔羊样噬菌体反映了重组依赖性生长的多种病毒策略

IF 7 2区生物学

Genome research Pub Date : 2025-07-10 DOI: 10.1101/gr.280248.124

Clarence Zheng, Sherwood R. Casjens, Alan R. Davidson, Susan K. Amundsen, Gerald R. Smith

{"title":"Lambdoid phages with abundant Chi recombination hotspots reflect diverse viral strategies for recombination-dependent growth","authors":"Clarence Zheng, Sherwood R. Casjens, Alan R. Davidson, Susan K. Amundsen, Gerald R. Smith","doi":"10.1101/gr.280248.124","DOIUrl":"https://doi.org/10.1101/gr.280248.124","url":null,"abstract":"Many phages encode recombination-mediating enzymes, but characterization of their roles in phage lifecycles is limited, and their impact on phage replication is controversial. To address these issues, we have searched for phages whose growth is impacted by the major recombination-promoting helicase-nuclease of Escherichia coli, the RecBCD enzyme. Although no phages inhibited by RecBCD are identified, growth of a newly isolated phage, named LLS, is enhanced by RecBCD. LLS's genome sequence reveals it is related to bacteriophage λ but encodes no recombination-promoting (Rec) proteins or associated RecBCD inhibitor. However, it contains an unexpectedly high number of Chi sites, activators of RecBCD-dependent recombination. Through analysis of 325 genomes of phages related to λ (lambdoid phages), we have found 71 other phage genomes that encode no Rec proteins but mostly possess large numbers of Chi sites. Conversely, phages encoding Rec proteins and a RecBCD inhibitor (collectively a Rec module) mostly lack Chi sites. Lambdoid phages of both diverse enteric bacteria and a pseudomonad have these properties. For this study, we thoroughly analyze the Rec modules of 246 lambdoid phage genomes. These analyses reveal a remarkable heterogeneity of Rec module protein types, both in sequence and in function, and allow us to identify phages that do not contain Rec modules. We conclude that phages lacking their own recombination systems have compensated by becoming enriched in Chi sites, enabling them to use the host's RecBCD to fulfill the requirement for recombination to efficiently replicate. This study highlights the importance of recombination for phage survival and the diversity of strategies to achieve it.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"688 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593970","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}

引用次数: 0

Integration of hyperspectral imaging and transcriptomics from individual cells with SpectralSeq 利用SpectralSeq整合来自单个细胞的高光谱成像和转录组学

IF 7 2区生物学

Genome research Pub Date : 2025-07-08 DOI: 10.1101/gr.280014.124

Yike Xie, Abbas Habibalahi, Ayad G. Anwer, Kanu Wahi, Jacqueline Bailey, Francis Lin, Catherine Gatt, Emma M.V. Johansson, Tatyana Chtanova, Jeff Holst, Ewa Goldys, Fabio Zanini

{"title":"Integration of hyperspectral imaging and transcriptomics from individual cells with SpectralSeq","authors":"Yike Xie, Abbas Habibalahi, Ayad G. Anwer, Kanu Wahi, Jacqueline Bailey, Francis Lin, Catherine Gatt, Emma M.V. Johansson, Tatyana Chtanova, Jeff Holst, Ewa Goldys, Fabio Zanini","doi":"10.1101/gr.280014.124","DOIUrl":"https://doi.org/10.1101/gr.280014.124","url":null,"abstract":"Microscopy and omics are complementary approaches to probe cellular molecular states in health and disease, combining granularity with scalability. However, integrating both imaging- and sequencing-based assays on the same cell has proven challenging. This study demonstrates a new approach called SpectralSeq that combines hyperspectral autofluorescence imaging with transcriptomics on the same cell. SpectralSeq is applied to Michigan Cancer Foundation-7 (MCF-7) breast cancer cells and identifies a subpopulation of cells exhibiting bright autofluorescence rings at the plasma membrane in optical channel 13 (λex = 431 nm, λem = 594 nm). Correlating the presence of a ring with the gene expression in the same cell indicates that ringed cells show higher expression of apoptosis-related genes and lower expression of ATP production genes. Furthermore, correlation of cell morphology with gene expression reveals downregulation of multiple spliceosome members in larger MCF-7 cells. Multiple genes exhibit consistent expression across cell sizes but varied exon usage. Finally, correlation between gene expression and fluorescence within the spectral range of nicotinamide adenine dinucleotide hydrogen (NADH) provides insights into the metabolic states of MCF-7 cells. Overall, SpectralSeq links optical spectrum with internal molecular states, offering a single streamlined workflow for single-cell resolution studies integrating spectral, morphological, and transcriptomic analyses.","PeriodicalId":12678,"journal":{"name":"Genome research","volume":"27 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586556","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}

引用次数: 0