Cell genomics最新文献_第8页

Missing regulatory effects and viral triggers explored for childhood-onset asthma. 探索儿童期哮喘的缺失调节效应和病毒诱因。

IF 11.1

Cell genomics Pub Date : 2024-09-11 DOI: 10.1016/j.xgen.2024.100652

Hai Fang

引用次数: 0

Genetic and functional analysis of Raynaud's syndrome implicates loci in vasculature and immunity. 雷诺氏综合征的遗传和功能分析涉及血管和免疫系统中的基因位点。

IF 11.1

Cell genomics Pub Date : 2024-09-11 Epub Date: 2024-08-13 DOI: 10.1016/j.xgen.2024.100630

Anniina Tervi, Markus Ramste, Erik Abner, Paul Cheng, Jacqueline M Lane, Matthew Maher, Jesse Valliere, Vilma Lammi, Satu Strausz, Juha Riikonen, Trieu Nguyen, Gabriella E Martyn, Maya U Sheth, Fan Xia, Mauro Lago Docampo, Wenduo Gu, Tõnu Esko, Richa Saxena, Matti Pirinen, Aarno Palotie, Samuli Ripatti, Nasa Sinnott-Armstrong, Mark Daly, Jesse M Engreitz, Marlene Rabinovitch, Caroline A Heckman, Thomas Quertermous, Samuel E Jones, Hanna M Ollila

{"title":"Genetic and functional analysis of Raynaud's syndrome implicates loci in vasculature and immunity.","authors":"Anniina Tervi, Markus Ramste, Erik Abner, Paul Cheng, Jacqueline M Lane, Matthew Maher, Jesse Valliere, Vilma Lammi, Satu Strausz, Juha Riikonen, Trieu Nguyen, Gabriella E Martyn, Maya U Sheth, Fan Xia, Mauro Lago Docampo, Wenduo Gu, Tõnu Esko, Richa Saxena, Matti Pirinen, Aarno Palotie, Samuli Ripatti, Nasa Sinnott-Armstrong, Mark Daly, Jesse M Engreitz, Marlene Rabinovitch, Caroline A Heckman, Thomas Quertermous, Samuel E Jones, Hanna M Ollila","doi":"10.1016/j.xgen.2024.100630","DOIUrl":"10.1016/j.xgen.2024.100630","url":null,"abstract":"Raynaud's syndrome is a dysautonomia where exposure to cold causes vasoconstriction and hypoxia, particularly in the extremities. We performed meta-analysis in four cohorts and discovered eight loci (ADRA2A, IRX1, NOS3, ACVR2A, TMEM51, PCDH10-DT, HLA, and RAB6C) where ADRA2A, ACVR2A, NOS3, TMEM51, and IRX1 co-localized with expression quantitative trait loci (eQTLs), particularly in distal arteries. CRISPR gene editing further showed that ADRA2A and NOS3 loci modified gene expression and in situ RNAscope clarified the specificity of ADRA2A in small vessels and IRX1 around small capillaries in the skin. A functional contraction assay in the cold showed lower contraction in ADRA2A-deficient and higher contraction in ADRA2A-overexpressing smooth muscle cells. Overall, our study highlights the power of genome-wide association testing with functional follow-up as a method to understand complex diseases. The results indicate temperature-dependent adrenergic signaling through ADRA2A, effects at the microvasculature by IRX1, endothelial signaling by NOS3, and immune mechanisms by the HLA locus in Raynaud's syndrome.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100630"},"PeriodicalIF":11.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141984069","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}

引用次数: 0

Predicting T cell receptor functionality against mutant epitopes. 预测 T 细胞受体对突变表位的功能。

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Cell genomics Pub Date : 2024-09-11 Epub Date: 2024-08-15 DOI: 10.1016/j.xgen.2024.100634

Felix Drost, Emilio Dorigatti, Adrian Straub, Philipp Hilgendorf, Karolin I Wagner, Kersten Heyer, Marta López Montes, Bernd Bischl, Dirk H Busch, Kilian Schober, Benjamin Schubert

{"title":"Predicting T cell receptor functionality against mutant epitopes.","authors":"Felix Drost, Emilio Dorigatti, Adrian Straub, Philipp Hilgendorf, Karolin I Wagner, Kersten Heyer, Marta López Montes, Bernd Bischl, Dirk H Busch, Kilian Schober, Benjamin Schubert","doi":"10.1016/j.xgen.2024.100634","DOIUrl":"10.1016/j.xgen.2024.100634","url":null,"abstract":"Cancer cells and pathogens can evade T cell receptors (TCRs) via mutations in immunogenic epitopes. TCR cross-reactivity (i.e., recognition of multiple epitopes with sequence similarities) can counteract such escape but may cause severe side effects in cell-based immunotherapies through targeting self-antigens. To predict the effect of epitope point mutations on T cell functionality, we here present the random forest-based model Predicting T Cell Epitope-Specific Activation against Mutant Versions (P-TEAM). P-TEAM was trained and tested on three datasets with TCR responses to single-amino-acid mutations of the model epitope SIINFEKL, the tumor neo-epitope VPSVWRSSL, and the human cytomegalovirus antigen NLVPMVATV, totaling 9,690 unique TCR-epitope interactions. P-TEAM was able to accurately classify T cell reactivities and quantitatively predict T cell functionalities for unobserved single-point mutations and unseen TCRs. Overall, P-TEAM provides an effective computational tool to study T cell responses against mutated epitopes.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100634"},"PeriodicalIF":11.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141997007","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}

引用次数: 0

Diversity of ribosomes at the level of rRNA variation associated with human health and disease. 与人类健康和疾病相关的 rRNA 变异水平上的核糖体多样性。

IF 11.1

Cell genomics Pub Date : 2024-09-11 Epub Date: 2024-08-06 DOI: 10.1016/j.xgen.2024.100629

Daphna Rothschild, Teodorus Theo Susanto, Xin Sui, Jeffrey P Spence, Ramya Rangan, Naomi R Genuth, Nasa Sinnott-Armstrong, Xiao Wang, Jonathan K Pritchard, Maria Barna

{"title":"Diversity of ribosomes at the level of rRNA variation associated with human health and disease.","authors":"Daphna Rothschild, Teodorus Theo Susanto, Xin Sui, Jeffrey P Spence, Ramya Rangan, Naomi R Genuth, Nasa Sinnott-Armstrong, Xiao Wang, Jonathan K Pritchard, Maria Barna","doi":"10.1016/j.xgen.2024.100629","DOIUrl":"10.1016/j.xgen.2024.100629","url":null,"abstract":"With hundreds of copies of rDNA, it is unknown whether they possess sequence variations that form different types of ribosomes. Here, we developed an algorithm for long-read variant calling, termed RGA, which revealed that variations in human rDNA loci are predominantly insertion-deletion (indel) variants. We developed full-length rRNA sequencing (RIBO-RT) and in situ sequencing (SWITCH-seq), which showed that translating ribosomes possess variation in rRNA. Over 1,000 variants are lowly expressed. However, tens of variants are abundant and form distinct rRNA subtypes with different structures near indels as revealed by long-read rRNA structure probing coupled to dimethyl sulfate sequencing. rRNA subtypes show differential expression in endoderm/ectoderm-derived tissues, and in cancer, low-abundance rRNA variants can become highly expressed. Together, this study identifies the diversity of ribosomes at the level of rRNA variants, their chromosomal location, and unique structure as well as the association of ribosome variation with tissue-specific biology and cancer.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100629"},"PeriodicalIF":11.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903761","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}

引用次数: 0

An isoform-resolution transcriptomic atlas of colorectal cancer from long-read single-cell sequencing. 利用长线程单细胞测序技术绘制结直肠癌同工酶分辨转录组图谱。

IF 11.1

Cell genomics Pub Date : 2024-09-11 Epub Date: 2024-08-30 DOI: 10.1016/j.xgen.2024.100641

Zhongxiao Li, Bin Zhang, Jia Jia Chan, Hossein Tabatabaeian, Qing Yun Tong, Xiao Hong Chew, Xiaonan Fan, Patrick Driguez, Charlene Chan, Faith Cheong, Shi Wang, Bei En Siew, Ian Jse-Wei Tan, Kai-Yin Lee, Bettina Lieske, Wai-Kit Cheong, Dennis Kappei, Ker-Kan Tan, Xin Gao, Yvonne Tay

{"title":"An isoform-resolution transcriptomic atlas of colorectal cancer from long-read single-cell sequencing.","authors":"Zhongxiao Li, Bin Zhang, Jia Jia Chan, Hossein Tabatabaeian, Qing Yun Tong, Xiao Hong Chew, Xiaonan Fan, Patrick Driguez, Charlene Chan, Faith Cheong, Shi Wang, Bei En Siew, Ian Jse-Wei Tan, Kai-Yin Lee, Bettina Lieske, Wai-Kit Cheong, Dennis Kappei, Ker-Kan Tan, Xin Gao, Yvonne Tay","doi":"10.1016/j.xgen.2024.100641","DOIUrl":"10.1016/j.xgen.2024.100641","url":null,"abstract":"Colorectal cancer (CRC) ranks as the second leading cause of cancer deaths globally. In recent years, short-read single-cell RNA sequencing (scRNA-seq) has been instrumental in deciphering tumor heterogeneities. However, these studies only enable gene-level quantification but neglect alterations in transcript structures arising from alternative end processing or splicing. In this study, we integrated short- and long-read scRNA-seq of CRC samples to build an isoform-resolution CRC transcriptomic atlas. We identified 394 dysregulated transcript structures in tumor epithelial cells, including 299 resulting from various combinations of splicing events. Second, we characterized genes and isoforms associated with epithelial lineages and subpopulations exhibiting distinct prognoses. Among 31,935 isoforms with novel junctions, 330 were supported by The Cancer Genome Atlas RNA-seq and mass spectrometry data. Finally, we built an algorithm that integrated novel peptides derived from open reading frames of recurrent tumor-specific transcripts with mass spectrometry data and identified recurring neoepitopes that may aid the development of cancer vaccines.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100641"},"PeriodicalIF":11.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115576","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}

引用次数: 0

Isotype-aware inference of B cell clonal lineage trees from single-cell sequencing data. 从单细胞测序数据推断同种型B细胞克隆系谱树。

IF 11.1

Cell genomics Pub Date : 2024-09-11 Epub Date: 2024-08-28 DOI: 10.1016/j.xgen.2024.100637

Leah L Weber, Derek Reiman, Mrinmoy S Roddur, Yuanyuan Qi, Mohammed El-Kebir, Aly A Khan

{"title":"Isotype-aware inference of B cell clonal lineage trees from single-cell sequencing data.","authors":"Leah L Weber, Derek Reiman, Mrinmoy S Roddur, Yuanyuan Qi, Mohammed El-Kebir, Aly A Khan","doi":"10.1016/j.xgen.2024.100637","DOIUrl":"10.1016/j.xgen.2024.100637","url":null,"abstract":"Single-cell RNA sequencing (scRNA-seq) enables comprehensive characterization of the micro-evolutionary processes of B cells during an adaptive immune response, capturing features of somatic hypermutation (SHM) and class switch recombination (CSR). Existing phylogenetic approaches for reconstructing B cell evolution have primarily focused on the SHM process alone. Here, we present tree inference of B cell clonal lineages (TRIBAL), an algorithm designed to optimally reconstruct the evolutionary history of B cell clonal lineages undergoing both SHM and CSR from scRNA-seq data. Through simulations, we demonstrate that TRIBAL produces more comprehensive and accurate B cell lineage trees compared to existing methods. Using real-world datasets, TRIBAL successfully recapitulates expected biological trends in a model affinity maturation system while reconstructing evolutionary histories with more parsimonious class switching than state-of-the-art methods. Thus, TRIBAL significantly improves B cell lineage tracing, useful for modeling vaccine responses, disease progression, and the identification of therapeutic antibodies.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100637"},"PeriodicalIF":11.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115577","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}

引用次数: 0

Analysis across Taiwan Biobank, Biobank Japan, and UK Biobank identifies hundreds of novel loci for 36 quantitative traits. 通过对台湾生物数据库、日本生物数据库和英国生物数据库的分析，确定了 36 个数量性状的数百个新基因位点。

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Cell genomics Pub Date : 2024-09-11 Epub Date: 2024-08-15 DOI: 10.1016/j.xgen.2024.100640

Chia-Yen Chen, Tzu-Ting Chen, Yen-Chen Anne Feng, Mingrui Yu, Shu-Chin Lin, Ryan J Longchamps, Shi-Heng Wang, Yi-Hsiang Hsu, Hwai-I Yang, Po-Hsiu Kuo, Mark J Daly, Wei J Chen, Hailiang Huang, Tian Ge, Yen-Feng Lin

引用次数: 0

Overcoming drug-resistant tumors with selection gene drives. 利用选择基因驱动克服耐药性肿瘤。

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Cell genomics Pub Date : 2024-09-11 DOI: 10.1016/j.xgen.2024.100653

Hui Wang, Mingqi Xie

引用次数: 0

Rhinovirus infection of airway epithelial cells uncovers the non-ciliated subset as a likely driver of genetic risk to childhood-onset asthma. 气道上皮细胞的鼻病毒感染揭示了非纤毛亚群可能是儿童期哮喘遗传风险的驱动因素。

IF 11.1

Cell genomics Pub Date : 2024-09-11 Epub Date: 2024-08-27 DOI: 10.1016/j.xgen.2024.100636

Sarah Djeddi, Daniela Fernandez-Salinas, George X Huang, Vitor R C Aguiar, Chitrasen Mohanty, Christina Kendziorski, Steven Gazal, Joshua A Boyce, Carole Ober, James E Gern, Nora A Barrett, Maria Gutierrez-Arcelus

{"title":"Rhinovirus infection of airway epithelial cells uncovers the non-ciliated subset as a likely driver of genetic risk to childhood-onset asthma.","authors":"Sarah Djeddi, Daniela Fernandez-Salinas, George X Huang, Vitor R C Aguiar, Chitrasen Mohanty, Christina Kendziorski, Steven Gazal, Joshua A Boyce, Carole Ober, James E Gern, Nora A Barrett, Maria Gutierrez-Arcelus","doi":"10.1016/j.xgen.2024.100636","DOIUrl":"10.1016/j.xgen.2024.100636","url":null,"abstract":"Asthma is a complex disease caused by genetic and environmental factors. Studies show that wheezing during rhinovirus infection correlates with childhood asthma development. Over 150 non-coding risk variants for asthma have been identified, many affecting gene regulation in T cells, but the effects of most risk variants remain unknown. We hypothesized that airway epithelial cells could also mediate genetic susceptibility to asthma given they are the first line of defense against respiratory viruses and allergens. We integrated genetic data with transcriptomics of airway epithelial cells subject to different stimuli. We demonstrate that rhinovirus infection significantly upregulates childhood-onset asthma-associated genes, particularly in non-ciliated cells. This enrichment is also observed with influenza infection but not with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or cytokine activation. Overall, our results suggest that rhinovirus infection is an environmental factor that interacts with genetic risk factors through non-ciliated airway epithelial cells to drive childhood-onset asthma.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100636"},"PeriodicalIF":11.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094262","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}

引用次数: 0

Genomic patterns of somatic mutations provide new prognostic, therapeutic, and biological insights in cancer. 体细胞突变的基因组模式为癌症的预后、治疗和生物学研究提供了新的视角。

IF 11.1

Cell genomics Pub Date : 2024-08-14 DOI: 10.1016/j.xgen.2024.100635

Dana Tseitline, Yuval Cohen, Sheera Adar

引用次数: 0