Cell genomics最新文献_第2页

Uncovering dark mass in population proteomics: Pan-analysis of single amino acid polymorphism relevant to cognition and aging.

IF 11.1

Cell genomics Pub Date : 2025-02-12 Epub Date: 2025-01-30 DOI: 10.1016/j.xgen.2025.100763

Xiaojing Gao, Yuanyuan Yin, Yiqian Chen, Ling Lu, Jian Zhao, Xu Lin, Jiarui Wu, Qingrun Li, Rong Zeng

{"title":"Uncovering dark mass in population proteomics: Pan-analysis of single amino acid polymorphism relevant to cognition and aging.","authors":"Xiaojing Gao, Yuanyuan Yin, Yiqian Chen, Ling Lu, Jian Zhao, Xu Lin, Jiarui Wu, Qingrun Li, Rong Zeng","doi":"10.1016/j.xgen.2025.100763","DOIUrl":"10.1016/j.xgen.2025.100763","url":null,"abstract":"Human proteome data across populations have been analyzed extensively to reveal protein quantitative associations with physiological or pathological states, while the single amino acid polymorphism (SAP) has been rarely investigated. In this work, we introduce a pan-SAP workflow that relies on pan-database searching independent of individual genome sequencing. Using ten cohorts comprising 2,004 individuals related to cognition disorder and aging, we quantify the SAP sites in key proteins, such as apolipoprotein E (APOE) in plasma and cerebrospinal fluid at the proteome level. Specifically, the quantification of heterozygous APOE-C112R, including its abundance and ratio, provides insights into the dosage effect and relationship with cognition disorder, which cannot be interpreted at the genomic level. Furthermore, our approach could precisely track age-related changes in APOE-C112R levels. Taken together, this pan-SAP workflow uncovered existing but hidden SAPs in multi-populations, connecting SAP quantification to disease progression and paving the way for broader proteomic investigations in complex diseases.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100763"},"PeriodicalIF":11.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076681","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}

引用次数: 0

Defining the regulatory logic of breast cancer using single-cell epigenetic and transcriptome profiling.

IF 11.1

Cell genomics Pub Date : 2025-02-12 Epub Date: 2025-02-05 DOI: 10.1016/j.xgen.2025.100765

Matthew J Regner, Susana Garcia-Recio, Aatish Thennavan, Kamila Wisniewska, Raul Mendez-Giraldez, Brooke Felsheim, Philip M Spanheimer, Joel S Parker, Charles M Perou, Hector L Franco

{"title":"Defining the regulatory logic of breast cancer using single-cell epigenetic and transcriptome profiling.","authors":"Matthew J Regner, Susana Garcia-Recio, Aatish Thennavan, Kamila Wisniewska, Raul Mendez-Giraldez, Brooke Felsheim, Philip M Spanheimer, Joel S Parker, Charles M Perou, Hector L Franco","doi":"10.1016/j.xgen.2025.100765","DOIUrl":"10.1016/j.xgen.2025.100765","url":null,"abstract":"Annotation of cis-regulatory elements that drive transcriptional dysregulation in cancer cells is critical to understanding tumor biology. Herein, we present matched chromatin accessibility (single-cell assay for transposase-accessible chromatin by sequencing [scATAC-seq]) and transcriptome (single-cell RNA sequencing [scRNA-seq]) profiles at single-cell resolution from human breast tumors and healthy mammary tissues processed immediately following surgical resection. We identify the most likely cell of origin for subtype-specific breast tumors and implement linear mixed-effects modeling to quantify associations between regulatory elements and gene expression in malignant versus normal cells. These data unveil cancer-specific regulatory elements and putative silencer-to-enhancer switching events in cells that lead to the upregulation of clinically relevant oncogenes. In addition, we generate matched scATAC-seq and scRNA-seq profiles for breast cancer cell lines, revealing a conserved oncogenic gene expression program between in vitro and in vivo cells. This work highlights the importance of non-coding regulatory mechanisms that underlie oncogenic processes and the ability of single-cell multi-omics to define the regulatory logic of cancer cells.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100765"},"PeriodicalIF":11.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366921","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}

引用次数: 0

Meet the author: Hector L. Franco.

IF 11.1

Cell genomics Pub Date : 2025-02-12 DOI: 10.1016/j.xgen.2025.100772

Hector L Franco

引用次数: 0

Tracing human trait evolution through integrative genomics and temporal annotations.

IF 11.1

Cell genomics Pub Date : 2025-02-12 Epub Date: 2025-01-24 DOI: 10.1016/j.xgen.2025.100767

Jian Zeng

引用次数: 0

Characterization and bioinformatic filtering of ambient gRNAs in single-cell CRISPR screens using CLEANSER.

IF 11.1

Cell genomics Pub Date : 2025-02-12 Epub Date: 2025-02-05 DOI: 10.1016/j.xgen.2025.100766

Siyan Liu, Marisa C Hamilton, Thomas Cowart, Alejandro Barrera, Lexi R Bounds, Alexander C Nelson, Sophie F Dornbaum, Julia W Riley, Richard W Doty, Andrew S Allen, Gregory E Crawford, William H Majoros, Charles A Gersbach

{"title":"Characterization and bioinformatic filtering of ambient gRNAs in single-cell CRISPR screens using CLEANSER.","authors":"Siyan Liu, Marisa C Hamilton, Thomas Cowart, Alejandro Barrera, Lexi R Bounds, Alexander C Nelson, Sophie F Dornbaum, Julia W Riley, Richard W Doty, Andrew S Allen, Gregory E Crawford, William H Majoros, Charles A Gersbach","doi":"10.1016/j.xgen.2025.100766","DOIUrl":"10.1016/j.xgen.2025.100766","url":null,"abstract":"Single-cell RNA sequencing CRISPR (perturb-seq) screens enable high-throughput investigation of the genome, allowing for characterization of thousands of genomic perturbations on gene expression. Ambient gRNAs, which are contaminating gRNAs, are a major source of noise in perturb-seq experiments because they result in an excess of false-positive gRNA assignments. Here, we utilize CRISPR barnyard assays to characterize ambient gRNAs in perturb-seq screens. We use these datasets to develop CRISPR Library Evaluation and Ambient Noise Suppression for Enhanced single-cell RNA-seq (CLEANSER), a mixture model that filters ambient gRNAs. CLEANSER includes both gRNA and cell-specific normalization parameters, correcting for confounding technical factors that affect individual gRNAs and cells. The output of CLEANSER is the probability that a gRNA-cell assignment is in the native distribution over the ambient distribution. We find that ambient gRNA filtering methods impact differential gene expression analysis outcomes and that CLEANSER outperforms alternate approaches by increasing gRNA-cell assignment accuracy across multiple screen formats.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100766"},"PeriodicalIF":11.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366918","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}

引用次数: 0

CRISPR-Cas spacer acquisition is a rare event in human gut microbiome. CRISPR-Cas间隔序列获取在人类肠道微生物组中是罕见的事件。

IF 11.1

Cell genomics Pub Date : 2025-01-08 Epub Date: 2024-12-23 DOI: 10.1016/j.xgen.2024.100725

An-Ni Zhang, Jeffry M Gaston, Pablo Cárdenas, Shijie Zhao, Xiaoqiong Gu, Eric J Alm

{"title":"CRISPR-Cas spacer acquisition is a rare event in human gut microbiome.","authors":"An-Ni Zhang, Jeffry M Gaston, Pablo Cárdenas, Shijie Zhao, Xiaoqiong Gu, Eric J Alm","doi":"10.1016/j.xgen.2024.100725","DOIUrl":"10.1016/j.xgen.2024.100725","url":null,"abstract":"Host-parasite relationships drive the evolution of both parties. In microbe-phage dynamics, CRISPR functions as an adaptive defense mechanism, updating immunity via spacer acquisition. Here, we investigated these interactions within the human gut microbiome, uncovering low frequencies of spacer acquisition at an average rate of one spacer every ∼2.9 point mutations using isolates' whole genomes and ∼2.7 years using metagenome time series. We identified a highly prevalent CRISPR array in Bifidobacterium longum spreading via horizontal gene transfer (HGT), with six spacers found in various genomic regions in 15 persons from the United States and Europe. These spacers, targeting two prominent Bifidobacterium phages, comprised 76% of spacer occurrence of all spacers targeting these phages in all B. longum populations. This result suggests that HGT of an entire CRISPR-Cas system introduced three times more spacers than local CRISPR-Cas acquisition in B. longum. Overall, our findings identified key ecological and evolutionary factors in prokaryote adaptive immunity.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100725"},"PeriodicalIF":11.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886552","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

Single-cell and spatial transcriptomic profiling revealed niche interactions sustaining growth of endometriotic lesions. 单细胞和空间转录组分析揭示了维持子宫内膜异位症病变生长的生态位相互作用。

IF 11.1

Cell genomics Pub Date : 2025-01-08 DOI: 10.1016/j.xgen.2024.100737

Song Liu, Xiaoyan Li, Zhiyue Gu, Jiayu Wu, Shuangzheng Jia, Jinghua Shi, Yi Dai, Yushi Wu, Hailan Yan, Jing Zhang, Yan You, Xiaowei Xue, Lulu Liu, Jinghe Lang, Xiaoyue Wang, Jinhua Leng

{"title":"Single-cell and spatial transcriptomic profiling revealed niche interactions sustaining growth of endometriotic lesions.","authors":"Song Liu, Xiaoyan Li, Zhiyue Gu, Jiayu Wu, Shuangzheng Jia, Jinghua Shi, Yi Dai, Yushi Wu, Hailan Yan, Jing Zhang, Yan You, Xiaowei Xue, Lulu Liu, Jinghe Lang, Xiaoyue Wang, Jinhua Leng","doi":"10.1016/j.xgen.2024.100737","DOIUrl":"10.1016/j.xgen.2024.100737","url":null,"abstract":"Endometriosis is a chronic condition with limited therapeutic options. The molecular aberrations promoting ectopic attachment and interactions with the local microenvironment sustaining lesion growth have been unclear, prohibiting development of targeted therapies. Here, we performed single-cell and spatial transcriptomic profiling of ectopic lesions and eutopic endometrium in endometriosis. We found that ectopic endometrial stromal (EnS) cells retained cyclical gene expression patterns of their eutopic counterparts while exhibiting unique gene expression that contributes to the pathogenesis of endometriosis. We identified two distinct ovarian stromal cells (OSCs) localized at different zones of the lesion, showing differential gene expression profiles associated with fibrosis and inflammation, respectively. We also identified WNT5A upregulation and aberrant activation of non-canonical WNT signaling in endometrial stromal cells that may contribute to the lesion establishment, offering novel targets for therapeutic intervention. These data will enhance our understanding of the molecular mechanisms underlying endometriosis and paves the way for developing non-hormonal treatments.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":"5 1","pages":"100737"},"PeriodicalIF":11.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142959859","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

Atlas-scale single-cell DNA methylation profiling with sciMETv3. 使用sciMETv3进行atlas级单细胞DNA甲基化分析。

IF 11.1

Cell genomics Pub Date : 2025-01-08 Epub Date: 2024-12-23 DOI: 10.1016/j.xgen.2024.100726

Ruth V Nichols, Lauren E Rylaarsdam, Brendan L O'Connell, Zohar Shipony, Nika Iremadze, Sonia N Acharya, Andrew C Adey

引用次数: 0

Meet the authors: Xiaoyue Wang and Jinhua Leng. 认识一下作者：王晓月和冷金华。

IF 11.1

Cell genomics Pub Date : 2025-01-08 DOI: 10.1016/j.xgen.2024.100742

Xiaoyue Wang, Jinhua Leng

引用次数: 0

Bridging genomics' greatest challenge: The diversity gap. 弥合基因组学最大的挑战：多样性差距。

IF 11.1

Cell genomics Pub Date : 2025-01-08 Epub Date: 2024-12-17 DOI: 10.1016/j.xgen.2024.100724

Manuel Corpas, Mkpouto Pius, Marie Poburennaya, Heinner Guio, Miriam Dwek, Shivashankar Nagaraj, Catalina Lopez-Correa, Alice Popejoy, Segun Fatumo

引用次数: 0