Cell genomicsPub Date : 2025-02-12DOI: 10.1016/j.xgen.2025.100772
Hector L Franco
{"title":"Meet the author: Hector L. Franco.","authors":"Hector L Franco","doi":"10.1016/j.xgen.2025.100772","DOIUrl":"https://doi.org/10.1016/j.xgen.2025.100772","url":null,"abstract":"<p><p>Hector Franco is a group leader at the University of Puerto Rico Comprehensive Cancer Center (UPRCCC), having re-located from the University of North Carolina in 2023. His laboratory focuses on gene regulation, non-coding RNA, and the tumor microenvironment. In this issue of Cell Genomics, his team presents the resource \"Defining the regulatory logic of breast cancer using single-cell epigenetic and transcriptome profiling,\" which highlights non-coding mechanisms of gene regulation in breast cancer.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":"5 2","pages":"100772"},"PeriodicalIF":11.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416450","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 : 2025-02-12Epub Date: 2025-02-05DOI: 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":"<p><p>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.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100766"},"PeriodicalIF":11.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366918","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 : 2025-02-12Epub Date: 2025-01-24DOI: 10.1016/j.xgen.2025.100767
Jian Zeng
{"title":"Tracing human trait evolution through integrative genomics and temporal annotations.","authors":"Jian Zeng","doi":"10.1016/j.xgen.2025.100767","DOIUrl":"10.1016/j.xgen.2025.100767","url":null,"abstract":"<p><p>Understanding the evolution of human traits is a fundamental yet challenging question. In a recent Cell Genomics article, Kun et al.<sup>1</sup> integrate large-scale genomic and phenotypic data, including deep-learning-derived imaging phenotypes, with temporal annotations to estimate the timing of evolutionary changes that led to differences in traits between modern humans and primates or hominin ancestors.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100767"},"PeriodicalIF":11.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11872422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043472","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 : 2025-01-08Epub Date: 2024-12-23DOI: 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":"<p><p>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.</p>","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}
{"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":"<p><p>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.</p>","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}
Cell genomicsPub Date : 2025-01-08Epub Date: 2024-12-23DOI: 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
{"title":"Atlas-scale single-cell DNA methylation profiling with sciMETv3.","authors":"Ruth V Nichols, Lauren E Rylaarsdam, Brendan L O'Connell, Zohar Shipony, Nika Iremadze, Sonia N Acharya, Andrew C Adey","doi":"10.1016/j.xgen.2024.100726","DOIUrl":"10.1016/j.xgen.2024.100726","url":null,"abstract":"<p><p>Single-cell methods to assess DNA methylation have not achieved the same level of cell throughput per experiment compared to other modalities, with large-scale datasets requiring extensive automation, time, and other resources. Here, we describe sciMETv3, a combinatorial indexing-based technique that enables atlas-scale libraries to be produced in a single experiment. To reduce the sequencing burden, we demonstrate the compatibility of sciMETv3 with capture techniques to enrich regulatory regions, as well as the ability to leverage enzymatic conversion, which can yield higher library diversity. We showcase the throughput of sciMETv3 by producing a >140,000 cell library from human middle frontal gyrus split across four multiplexed individuals using both Illumina and Ultima sequencing instrumentation. Finally, we introduce sciMET+ATAC to enable high-throughput exploration of the interplay between chromatin accessibility and DNA methylation within the same cell.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100726"},"PeriodicalIF":11.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886551","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 : 2025-01-08DOI: 10.1016/j.xgen.2024.100742
Xiaoyue Wang, Jinhua Leng
{"title":"Meet the authors: Xiaoyue Wang and Jinhua Leng.","authors":"Xiaoyue Wang, Jinhua Leng","doi":"10.1016/j.xgen.2024.100742","DOIUrl":"10.1016/j.xgen.2024.100742","url":null,"abstract":"<p><p>We talk to Xiaoyue Wang and Jinhua Leng, corresponding authors of \"Single-cell and spatial transcriptomic profiling revealed niche interactions sustaining growth of endometriotic lesions\" in this issue of Cell Genomics, about their research, the key implications of their study, and their advice for other scientists.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":"5 1","pages":"100742"},"PeriodicalIF":11.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142959766","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 : 2025-01-08Epub Date: 2024-12-17DOI: 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
{"title":"Bridging genomics' greatest challenge: The diversity gap.","authors":"Manuel Corpas, Mkpouto Pius, Marie Poburennaya, Heinner Guio, Miriam Dwek, Shivashankar Nagaraj, Catalina Lopez-Correa, Alice Popejoy, Segun Fatumo","doi":"10.1016/j.xgen.2024.100724","DOIUrl":"10.1016/j.xgen.2024.100724","url":null,"abstract":"<p><p>Achieving diverse representation in biomedical data is critical for healthcare equity. Failure to do so perpetuates health disparities and exacerbates biases that may harm patients with underrepresented ancestral backgrounds. We present a quantitative assessment of representation in datasets used across human genomics, including genome-wide association studies (GWASs), pharmacogenomics, clinical trials, and direct-to-consumer (DTC) genetic testing. We suggest that relative proportions of ancestries represented in datasets, compared to the global census population, provide insufficient representation of global ancestral genetic diversity. Some populations have greater proportional representation in data relative to their population size and the genomic diversity present in their ancestral haplotypes. As insights from genomics become increasingly integrated into evidence-based medicine, strategic inclusion and effective mechanisms to ensure representation of global genomic diversity in datasets are imperative.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100724"},"PeriodicalIF":11.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856862","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 : 2025-01-08DOI: 10.1016/j.xgen.2024.100739
Xueying Liu, Richard H Chapple, Declan Bennett, William C Wright, Ankita Sanjali, Erielle Culp, Yinwen Zhang, Min Pan, Paul Geeleher
{"title":"CSI-GEP: A GPU-based unsupervised machine learning approach for recovering gene expression programs in atlas-scale single-cell RNA-seq data.","authors":"Xueying Liu, Richard H Chapple, Declan Bennett, William C Wright, Ankita Sanjali, Erielle Culp, Yinwen Zhang, Min Pan, Paul Geeleher","doi":"10.1016/j.xgen.2024.100739","DOIUrl":"10.1016/j.xgen.2024.100739","url":null,"abstract":"<p><p>Exploratory analysis of single-cell RNA sequencing (scRNA-seq) typically relies on hard clustering over two-dimensional projections like uniform manifold approximation and projection (UMAP). However, such methods can severely distort the data and have many arbitrary parameter choices. Methods that can model scRNA-seq data as non-discrete \"gene expression programs\" (GEPs) can better preserve the data's structure, but currently, they are often not scalable, not consistent across repeated runs, and lack an established method for choosing key parameters. Here, we developed a GPU-based unsupervised learning approach, \"consensus and scalable inference of gene expression programs\" (CSI-GEP). We show that CSI-GEP can recover ground truth GEPs in real and simulated atlas-scale scRNA-seq datasets, significantly outperforming cutting-edge methods, including GPT-based neural networks. We applied CSI-GEP to a whole mouse brain atlas of 2.2 million cells, disentangling endothelial cell types missed by other methods, and to an integrated scRNA-seq atlas of human tumors and cell lines, discovering mesenchymal-like GEPs unique to cancer cells growing in culture.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":"5 1","pages":"100739"},"PeriodicalIF":11.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142959844","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 : 2025-01-08DOI: 10.1016/j.xgen.2024.100741
Shahar Silverman, Diyendo Massilani
{"title":"Double or nothing: Ancient duplications in the amylase locus drove human adaptation.","authors":"Shahar Silverman, Diyendo Massilani","doi":"10.1016/j.xgen.2024.100741","DOIUrl":"10.1016/j.xgen.2024.100741","url":null,"abstract":"<p><p>Salivary and pancreatic amylase are encoded by AMY1 and AMY2, respectively, which are located within a single genomic locus that has undergone substantial structural variation, resulting in varying gene copy numbers across species. Using optical genome mapping and long-read sequencing, Yilmaz, Karageorgiou, Kim, et al. achieved nucleotide-level resolution of this locus across different human populations, offering new insights into how copy number variation contributes to human adaptation.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":"5 1","pages":"100741"},"PeriodicalIF":11.1,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142959851","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}