Cell genomics最新文献_第10页

Identifying compound-protein interactions with knowledge graph embedding of perturbation transcriptomics. 通过扰动转录组学的知识图嵌入识别化合物与蛋白质之间的相互作用。

IF 11.1

Cell genomics Pub Date : 2024-10-09 Epub Date: 2024-09-19 DOI: 10.1016/j.xgen.2024.100655

Shengkun Ni, Xiangtai Kong, Yingying Zhang, Zhengyang Chen, Zhaokun Wang, Zunyun Fu, Ruifeng Huo, Xiaochu Tong, Ning Qu, Xiaolong Wu, Kun Wang, Wei Zhang, Runze Zhang, Zimei Zhang, Jiangshan Shi, Yitian Wang, Ruirui Yang, Xutong Li, Sulin Zhang, Mingyue Zheng

{"title":"Identifying compound-protein interactions with knowledge graph embedding of perturbation transcriptomics.","authors":"Shengkun Ni, Xiangtai Kong, Yingying Zhang, Zhengyang Chen, Zhaokun Wang, Zunyun Fu, Ruifeng Huo, Xiaochu Tong, Ning Qu, Xiaolong Wu, Kun Wang, Wei Zhang, Runze Zhang, Zimei Zhang, Jiangshan Shi, Yitian Wang, Ruirui Yang, Xutong Li, Sulin Zhang, Mingyue Zheng","doi":"10.1016/j.xgen.2024.100655","DOIUrl":"10.1016/j.xgen.2024.100655","url":null,"abstract":"The emergence of perturbation transcriptomics provides a new perspective for drug discovery, but existing analysis methods suffer from inadequate performance and limited applicability. In this work, we present PertKGE, a method designed to deconvolute compound-protein interactions from perturbation transcriptomics with knowledge graph embedding. By considering multi-level regulatory events within biological systems that share the same semantic context, PertKGE significantly improves deconvoluting accuracy in two critical \"cold-start\" settings: inferring targets for new compounds and conducting virtual screening for new targets. We further demonstrate the pivotal role of incorporating multi-level regulatory events in alleviating representational biases. Notably, it enables the identification of ectonucleotide pyrophosphatase/phosphodiesterase-1 as the target responsible for the unique anti-tumor immunotherapy effect of tankyrase inhibitor K-756 and the discovery of five novel hits targeting the emerging cancer therapeutic target aldehyde dehydrogenase 1B1 with a remarkable hit rate of 10.2%. These findings highlight the potential of PertKGE to accelerate drug discovery.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100655"},"PeriodicalIF":11.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302298","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

CXCR4 orchestrates the TOX-programmed exhausted phenotype of CD8⁺ T cells via JAK2/STAT3 pathway. CXCR4 通过 JAK2/STAT3 通路协调 CD8+ T 细胞的毒素编程衰竭表型。

IF 11.1

Cell genomics Pub Date : 2024-10-09 Epub Date: 2024-09-23 DOI: 10.1016/j.xgen.2024.100659

Canhui Cao, Miaochun Xu, Ye Wei, Ting Peng, Shitong Lin, Xiaojie Liu, Yashi Xu, Tian Chu, Shiyi Liu, Ping Wu, Bai Hu, Wencheng Ding, Li Li, Ding Ma, Peng Wu

{"title":"CXCR4 orchestrates the TOX-programmed exhausted phenotype of CD8+ T cells via JAK2/STAT3 pathway.","authors":"Canhui Cao, Miaochun Xu, Ye Wei, Ting Peng, Shitong Lin, Xiaojie Liu, Yashi Xu, Tian Chu, Shiyi Liu, Ping Wu, Bai Hu, Wencheng Ding, Li Li, Ding Ma, Peng Wu","doi":"10.1016/j.xgen.2024.100659","DOIUrl":"10.1016/j.xgen.2024.100659","url":null,"abstract":"Evidence from clinical trials suggests that CXCR4 antagonists enhance immunotherapy effectiveness in several cancers. However, the specific mechanisms through which CXCR4 contributes to immune cell phenotypes are not fully understood. Here, we employed single-cell transcriptomic analysis and identified CXCR4 as a marker gene in T cells, with CD8+PD-1high exhausted T (Tex) cells exhibiting high CXCR4 expression. By blocking CXCR4, the Tex phenotype was attenuated in vivo. Mechanistically, CXCR4-blocking T cells mitigated the Tex phenotype by regulating the JAK2-STAT3 pathway. Single-cell RNA/TCR/ATAC-seq confirmed that Cxcr4-deficient CD8+ T cells epigenetically mitigated the transition from functional to exhausted phenotypes. Notably, clinical sample analysis revealed that CXCR4+CD8+ T cells showed higher expression in patients with a non-complete pathological response. Collectively, these findings demonstrate the mechanism by which CXCR4 orchestrates CD8+ Tex cells and provide a rationale for combining CXCR4 antagonists with immunotherapy in clinical trials.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100659"},"PeriodicalIF":11.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333608","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

A genome-wide association study of neonatal metabolites. 新生儿代谢物的全基因组关联研究。

IF 11.1

Cell genomics Pub Date : 2024-10-09 DOI: 10.1016/j.xgen.2024.100668

Quanze He, Hankui Liu, Lu Lu, Qin Zhang, Qi Wang, Benjing Wang, Xiaojuan Wu, Liping Guan, Jun Mao, Ying Xue, Chunhua Zhang, Xinye Cao, Yuxing He, Xiangwen Peng, Huanhuan Peng, Kangrong Zhao, Hong Li, Xin Jin, Lijian Zhao, Jianguo Zhang, Ting Wang

引用次数: 0

The hidden costs of aneuploidy: New insights from yeast. 非整倍体的隐性成本：来自酵母的新见解

IF 11.1

Cell genomics Pub Date : 2024-10-09 DOI: 10.1016/j.xgen.2024.100673

Yuerong Wang, Xian Fu, Yue Shen

引用次数: 0

Unlocking the genetic influence on milk variation and its potential implication for infant health. 揭示基因对牛奶变异的影响及其对婴儿健康的潜在影响。

IF 11.1

Cell genomics Pub Date : 2024-10-09 DOI: 10.1016/j.xgen.2024.100676

Claudia Nussbaum, Sarah Kim-Hellmuth

引用次数: 0

Genome-wide association study of maternal plasma metabolites during pregnancy. 孕期母体血浆代谢物的全基因组关联研究。

IF 11.1

Cell genomics Pub Date : 2024-10-09 DOI: 10.1016/j.xgen.2024.100657

Siyang Liu, Jilong Yao, Liang Lin, Xianmei Lan, Linlin Wu, Xuelian He, Nannan Kong, Yan Li, Yuqing Deng, Jiansheng Xie, Huanhuan Zhu, Xiaoxia Wu, Zilong Li, Likuan Xiong, Yuan Wang, Jinghui Ren, Xuemei Qiu, Weihua Zhao, Ya Gao, Yuanqing Chen, Fengxia Su, Yun Zhou, Weiqiao Rao, Jing Zhang, Guixue Hou, Liping Huang, Linxuan Li, Xinhong Liu, Chao Nie, Liqiong Luo, Mei Zhao, Zengyou Liu, Fang Chen, Shengmou Lin, Lijian Zhao, Qingmei Fu, Dan Jiang, Ye Yin, Xun Xu, Jian Wang, Huanming Yang, Rong Wang, Jianmin Niu, Fengxiang Wei, Xin Jin, Siqi Liu

{"title":"Genome-wide association study of maternal plasma metabolites during pregnancy.","authors":"Siyang Liu, Jilong Yao, Liang Lin, Xianmei Lan, Linlin Wu, Xuelian He, Nannan Kong, Yan Li, Yuqing Deng, Jiansheng Xie, Huanhuan Zhu, Xiaoxia Wu, Zilong Li, Likuan Xiong, Yuan Wang, Jinghui Ren, Xuemei Qiu, Weihua Zhao, Ya Gao, Yuanqing Chen, Fengxia Su, Yun Zhou, Weiqiao Rao, Jing Zhang, Guixue Hou, Liping Huang, Linxuan Li, Xinhong Liu, Chao Nie, Liqiong Luo, Mei Zhao, Zengyou Liu, Fang Chen, Shengmou Lin, Lijian Zhao, Qingmei Fu, Dan Jiang, Ye Yin, Xun Xu, Jian Wang, Huanming Yang, Rong Wang, Jianmin Niu, Fengxiang Wei, Xin Jin, Siqi Liu","doi":"10.1016/j.xgen.2024.100657","DOIUrl":"10.1016/j.xgen.2024.100657","url":null,"abstract":"Metabolites are key indicators of health and therapeutic targets, but their genetic underpinnings during pregnancy-a critical period for human reproduction-are largely unexplored. Using genetic data from non-invasive prenatal testing, we performed a genome-wide association study on 84 metabolites, including 37 amino acids, 24 elements, 13 hormones, and 10 vitamins, involving 34,394 pregnant Chinese women, with sample sizes ranging from 6,394 to 13,392 for specific metabolites. We identified 53 metabolite-gene associations, 23 of which are novel. Significant differences in genetic effects between pregnant and non-pregnant women were observed for 16.7%-100% of these associations, indicating gene-environment interactions. Additionally, 50.94% of genetic associations exhibited pleiotropy among metabolites and between six metabolites and eight pregnancy phenotypes. Mendelian randomization revealed potential causal relationships between seven maternal metabolites and 15 human traits and diseases. These findings provide new insights into the genetic basis of maternal plasma metabolites during pregnancy.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":"4 10","pages":"100657"},"PeriodicalIF":11.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402180","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

FUSE: Improving the estimation and imputation of variant impacts in functional screening. FUSE：改进功能筛选中变异影响的估计和估算。

IF 11.1

Cell genomics Pub Date : 2024-10-09 DOI: 10.1016/j.xgen.2024.100667

Tian Yu, James D Fife, Vineel Bhat, Ivan Adzhubey, Richard Sherwood, Christopher A Cassa

{"title":"FUSE: Improving the estimation and imputation of variant impacts in functional screening.","authors":"Tian Yu, James D Fife, Vineel Bhat, Ivan Adzhubey, Richard Sherwood, Christopher A Cassa","doi":"10.1016/j.xgen.2024.100667","DOIUrl":"10.1016/j.xgen.2024.100667","url":null,"abstract":"Deep mutational scanning enables high-throughput functional assessment of genetic variants. While phenotypic measurements from screening assays generally align with clinical outcomes, experimental noise may affect the accuracy of individual variant estimates. We developed the FUSE (functional substitution estimation) pipeline, which leverages measurements collectively within screening assays to improve the estimation of variant impacts. Drawing data from 115 published functional assays, FUSE assesses the mean functional effect per amino acid position and makes estimates for individual allelic variants. It enhances the correlation of variant functional effects from different assay platforms and increases the classification accuracy of missense variants in ClinVar across 29 genes (area under the receiver operating characteristic [ROC] curve [AUC] from 0.83 to 0.90). In UK Biobank patients with rare missense variants in BRCA1, LDLR, or TP53, FUSE improves the classification accuracy of associated phenotypes. FUSE can also impute variant effects for substitutions not experimentally screened. This approach improves accuracy and broadens the utility of data from functional screening.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":"4 10","pages":"100667"},"PeriodicalIF":11.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402203","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

Stable and robust Xi and Y transcriptomes drive cell-type-specific autosomal and Xa responses in vivo and in vitro in four human cell types. 在四种人类细胞类型中，稳定而强大的Xi和Y转录组在体内和体外驱动细胞类型特异的常染色体和Xa反应。

IF 11.1

Cell genomics Pub Date : 2024-09-11 Epub Date: 2024-08-06 DOI: 10.1016/j.xgen.2024.100628

Laura V Blanton, Adrianna K San Roman, Geryl Wood, Ashley Buscetta, Nicole Banks, Helen Skaletsky, Alexander K Godfrey, Thao T Pham, Jennifer F Hughes, Laura G Brown, Paul Kruszka, Angela E Lin, Daniel L Kastner, Maximilian Muenke, David C Page

{"title":"Stable and robust Xi and Y transcriptomes drive cell-type-specific autosomal and Xa responses in vivo and in vitro in four human cell types.","authors":"Laura V Blanton, Adrianna K San Roman, Geryl Wood, Ashley Buscetta, Nicole Banks, Helen Skaletsky, Alexander K Godfrey, Thao T Pham, Jennifer F Hughes, Laura G Brown, Paul Kruszka, Angela E Lin, Daniel L Kastner, Maximilian Muenke, David C Page","doi":"10.1016/j.xgen.2024.100628","DOIUrl":"10.1016/j.xgen.2024.100628","url":null,"abstract":"Recent in vitro studies of human sex chromosome aneuploidy showed that the Xi (\"inactive\" X) and Y chromosomes broadly modulate autosomal and Xa (\"active\" X) gene expression. We tested these findings in vivo. Linear modeling of CD4+ T cells and monocytes from individuals with one to three X chromosomes and zero to two Y chromosomes revealed 82 sex-chromosomal and 344 autosomal genes whose expression changed significantly with Xi and/or Y dosage in vivo. Changes in sex-chromosomal expression were remarkably constant in vivo and in vitro; autosomal responses to Xi and/or Y dosage were largely cell-type specific (∼2.6-fold more variation than sex-chromosomal responses). Targets of the sex-chromosomal transcription factors ZFX and ZFY accounted for a significant fraction of these autosomal responses both in vivo and in vitro. We conclude that the human Xi and Y transcriptomes are surprisingly robust and stable, yet they modulate autosomal and Xa genes in a cell-type-specific fashion.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100628"},"PeriodicalIF":11.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903762","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

ONCOLINER: A new solution for monitoring, improving, and harmonizing somatic variant calling across genomic oncology centers. ONCOLINER：用于监测、改进和协调各基因组肿瘤中心体细胞变异调用的新解决方案。

IF 11.1

Cell genomics Pub Date : 2024-09-11 Epub Date: 2024-08-30 DOI: 10.1016/j.xgen.2024.100639

Rodrigo Martín, Nicolás Gaitán, Frédéric Jarlier, Lars Feuerbach, Henri de Soyres, Marc Arbonés, Tom Gutman, Montserrat Puiggròs, Alvaro Ferriz, Asier Gonzalez, Lucía Estelles, Ivo Gut, Salvador Capella-Gutierrez, Lincoln D Stein, Benedikt Brors, Romina Royo, Philippe Hupé, David Torrents

{"title":"ONCOLINER: A new solution for monitoring, improving, and harmonizing somatic variant calling across genomic oncology centers.","authors":"Rodrigo Martín, Nicolás Gaitán, Frédéric Jarlier, Lars Feuerbach, Henri de Soyres, Marc Arbonés, Tom Gutman, Montserrat Puiggròs, Alvaro Ferriz, Asier Gonzalez, Lucía Estelles, Ivo Gut, Salvador Capella-Gutierrez, Lincoln D Stein, Benedikt Brors, Romina Royo, Philippe Hupé, David Torrents","doi":"10.1016/j.xgen.2024.100639","DOIUrl":"10.1016/j.xgen.2024.100639","url":null,"abstract":"The characterization of somatic genomic variation associated with the biology of tumors is fundamental for cancer research and personalized medicine, as it guides the reliability and impact of cancer studies and genomic-based decisions in clinical oncology. However, the quality and scope of tumor genome analysis across cancer research centers and hospitals are currently highly heterogeneous, limiting the consistency of tumor diagnoses across hospitals and the possibilities of data sharing and data integration across studies. With the aim of providing users with actionable and personalized recommendations for the overall enhancement and harmonization of somatic variant identification across research and clinical environments, we have developed ONCOLINER. Using specifically designed mosaic and tumorized genomes for the analysis of recall and precision across somatic SNVs, insertions or deletions (indels), and structural variants (SVs), we demonstrate that ONCOLINER is capable of improving and harmonizing genome analysis across three state-of-the-art variant discovery pipelines in genomic oncology.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100639"},"PeriodicalIF":11.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115578","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

Ribosomes unraveled: The path from variant to impact. 解开核糖体：从变异到影响的路径

IF 11.1

Cell genomics Pub Date : 2024-09-11 DOI: 10.1016/j.xgen.2024.100658

Paxton Kostos, Anna Galligos, Jennifer L Gerton

引用次数: 0