Cell genomics最新文献_第5页

Meningioma transcriptomic landscape demonstrates novel subtypes with regional associated biology and patient outcome. 脑膜瘤转录组图谱显示了与区域生物学和患者预后相关的新型亚型。

IF 11.1

Cell genomics Pub Date : 2024-06-12 Epub Date: 2024-05-23 DOI: 10.1016/j.xgen.2024.100566

H Nayanga Thirimanne, Damian Almiron-Bonnin, Nicholas Nuechterlein, Sonali Arora, Matt Jensen, Carolina A Parada, Chengxiang Qiu, Frank Szulzewsky, Collin W English, William C Chen, Philipp Sievers, Farshad Nassiri, Justin Z Wang, Tiemo J Klisch, Kenneth D Aldape, Akash J Patel, Patrick J Cimino, Gelareh Zadeh, Felix Sahm, David R Raleigh, Jay Shendure, Manuel Ferreira, Eric C Holland

{"title":"Meningioma transcriptomic landscape demonstrates novel subtypes with regional associated biology and patient outcome.","authors":"H Nayanga Thirimanne, Damian Almiron-Bonnin, Nicholas Nuechterlein, Sonali Arora, Matt Jensen, Carolina A Parada, Chengxiang Qiu, Frank Szulzewsky, Collin W English, William C Chen, Philipp Sievers, Farshad Nassiri, Justin Z Wang, Tiemo J Klisch, Kenneth D Aldape, Akash J Patel, Patrick J Cimino, Gelareh Zadeh, Felix Sahm, David R Raleigh, Jay Shendure, Manuel Ferreira, Eric C Holland","doi":"10.1016/j.xgen.2024.100566","DOIUrl":"10.1016/j.xgen.2024.100566","url":null,"abstract":"Meningiomas, although mostly benign, can be recurrent and fatal. World Health Organization (WHO) grading of the tumor does not always identify high-risk meningioma, and better characterizations of their aggressive biology are needed. To approach this problem, we combined 13 bulk RNA sequencing (RNA-seq) datasets to create a dimension-reduced reference landscape of 1,298 meningiomas. The clinical and genomic metadata effectively correlated with landscape regions, which led to the identification of meningioma subtypes with specific biological signatures. The time to recurrence also correlated with the map location. Further, we developed an algorithm that maps new patients onto this landscape, where the nearest neighbors predict outcome. This study highlights the utility of combining bulk transcriptomic datasets to visualize the complexity of tumor populations. Further, we provide an interactive tool for understanding the disease and predicting patient outcomes. This resource is accessible via the online tool Oncoscape, where the scientific community can explore the meningioma landscape.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11228955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094730","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

Shaping human brain development and vulnerability through alternative splicing. 通过替代剪接塑造人类大脑的发育和脆弱性。

IF 11.1

Cell genomics Pub Date : 2024-06-12 DOI: 10.1016/j.xgen.2024.100584

Francisco Aya, Juan Valcárcel

引用次数: 0

Molecular adaptations in response to exercise training are associated with tissue-specific transcriptomic and epigenomic signatures. 运动训练的分子适应与组织特异性转录组和表观基因组特征有关。

IF 11.1

Cell genomics Pub Date : 2024-06-12 Epub Date: 2024-05-01 DOI: 10.1016/j.xgen.2023.100421

Venugopalan D Nair, Hanna Pincas, Gregory R Smith, Elena Zaslavsky, Yongchao Ge, Mary Anne S Amper, Mital Vasoya, Maria Chikina, Yifei Sun, Archana Natarajan Raja, Weiguang Mao, Nicole R Gay, Karyn A Esser, Kevin S Smith, Bingqing Zhao, Laurens Wiel, Aditya Singh, Malene E Lindholm, David Amar, Stephen Montgomery, Michael P Snyder, Martin J Walsh, Stuart C Sealfon

{"title":"Molecular adaptations in response to exercise training are associated with tissue-specific transcriptomic and epigenomic signatures.","authors":"Venugopalan D Nair, Hanna Pincas, Gregory R Smith, Elena Zaslavsky, Yongchao Ge, Mary Anne S Amper, Mital Vasoya, Maria Chikina, Yifei Sun, Archana Natarajan Raja, Weiguang Mao, Nicole R Gay, Karyn A Esser, Kevin S Smith, Bingqing Zhao, Laurens Wiel, Aditya Singh, Malene E Lindholm, David Amar, Stephen Montgomery, Michael P Snyder, Martin J Walsh, Stuart C Sealfon","doi":"10.1016/j.xgen.2023.100421","DOIUrl":"10.1016/j.xgen.2023.100421","url":null,"abstract":"Regular exercise has many physical and brain health benefits, yet the molecular mechanisms mediating exercise effects across tissues remain poorly understood. Here we analyzed 400 high-quality DNA methylation, ATAC-seq, and RNA-seq datasets from eight tissues from control and endurance exercise-trained (EET) rats. Integration of baseline datasets mapped the gene location dependence of epigenetic control features and identified differing regulatory landscapes in each tissue. The transcriptional responses to 8 weeks of EET showed little overlap across tissues and predominantly comprised tissue-type enriched genes. We identified sex differences in the transcriptomic and epigenomic changes induced by EET. However, the sex-biased gene responses were linked to shared signaling pathways. We found that many G protein-coupled receptor-encoding genes are regulated by EET, suggesting a role for these receptors in mediating the molecular adaptations to training across tissues. Our findings provide new insights into the mechanisms underlying EET-induced health benefits across organs.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11228891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863863","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

Complementation testing identifies genes mediating effects at quantitative trait loci underlying fear-related behavior. 互补测试确定了恐惧相关行为的数量性状基因座的中介效应基因。

Cell genomics Pub Date : 2024-05-08 Epub Date: 2024-05-01 DOI: 10.1016/j.xgen.2024.100545

Patrick B Chen, Rachel Chen, Nathan LaPierre, Zeyuan Chen, Joel Mefford, Emilie Marcus, Matthew G Heffel, Daniela C Soto, Jason Ernst, Chongyuan Luo, Jonathan Flint

{"title":"Complementation testing identifies genes mediating effects at quantitative trait loci underlying fear-related behavior.","authors":"Patrick B Chen, Rachel Chen, Nathan LaPierre, Zeyuan Chen, Joel Mefford, Emilie Marcus, Matthew G Heffel, Daniela C Soto, Jason Ernst, Chongyuan Luo, Jonathan Flint","doi":"10.1016/j.xgen.2024.100545","DOIUrl":"10.1016/j.xgen.2024.100545","url":null,"abstract":"Knowing the genes involved in quantitative traits provides an entry point to understanding the biological bases of behavior, but there are very few examples where the pathway from genetic locus to behavioral change is known. To explore the role of specific genes in fear behavior, we mapped three fear-related traits, tested fourteen genes at six quantitative trait loci (QTLs) by quantitative complementation, and identified six genes. Four genes, Lamp, Ptprd, Nptx2, and Sh3gl, have known roles in synapse function; the fifth, Psip1, was not previously implicated in behavior; and the sixth is a long non-coding RNA, 4933413L06Rik, of unknown function. Variation in transcriptome and epigenetic modalities occurred preferentially in excitatory neurons, suggesting that genetic variation is more permissible in excitatory than inhibitory neuronal circuits. Our results relieve a bottleneck in using genetic mapping of QTLs to uncover biology underlying behavior and prompt a reconsideration of expected relationships between genetic and functional variation.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11099346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140860711","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

The landscape of cancer-rewired GPCR signaling axes. 癌症重构的 GPCR 信号轴。

Cell genomics Pub Date : 2024-05-08 DOI: 10.1016/j.xgen.2024.100557

Chakit Arora, Marin Matic, Luisa Bisceglia, Pierluigi Di Chiaro, Natalia De Oliveira Rosa, Francesco Carli, Lauren Clubb, Lorenzo Amir Nemati Fard, Giorgos Kargas, Giuseppe R Diaferia, Ranka Vukotic, Luana Licata, Guanming Wu, Gioacchino Natoli, J Silvio Gutkind, Francesco Raimondi

{"title":"The landscape of cancer-rewired GPCR signaling axes.","authors":"Chakit Arora, Marin Matic, Luisa Bisceglia, Pierluigi Di Chiaro, Natalia De Oliveira Rosa, Francesco Carli, Lauren Clubb, Lorenzo Amir Nemati Fard, Giorgos Kargas, Giuseppe R Diaferia, Ranka Vukotic, Luana Licata, Guanming Wu, Gioacchino Natoli, J Silvio Gutkind, Francesco Raimondi","doi":"10.1016/j.xgen.2024.100557","DOIUrl":"10.1016/j.xgen.2024.100557","url":null,"abstract":"We explored the dysregulation of G-protein-coupled receptor (GPCR) ligand systems in cancer transcriptomics datasets to uncover new therapeutics opportunities in oncology. We derived an interaction network of receptors with ligands and their biosynthetic enzymes. Multiple GPCRs are differentially regulated together with their upstream partners across cancer subtypes and are associated to specific transcriptional programs and to patient survival patterns. The expression of both receptor-ligand (or enzymes) partners improved patient stratification, suggesting a synergistic role for the activation of GPCR networks in modulating cancer phenotypes. Remarkably, we identified many such axes across several cancer molecular subtypes, including many involving receptor-biosynthetic enzymes for neurotransmitters. We found that GPCRs from these actionable axes, including, e.g., muscarinic, adenosine, 5-hydroxytryptamine, and chemokine receptors, are the targets of multiple drugs displaying anti-growth effects in large-scale, cancer cell drug screens, which we further validated. We have made the results generated in this study freely available through a webapp (gpcrcanceraxes.bioinfolab.sns.it).","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11099383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140900701","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

Exploring GPCR signaling pathway networks as cancer therapeutic targets. 探索作为癌症治疗靶点的 GPCR 信号通路网络。

Cell genomics Pub Date : 2024-05-08 DOI: 10.1016/j.xgen.2024.100560

Balaji Santhanam, Madison Sluter, M Madan Babu

引用次数: 0

Cis-regulatory control of transcriptional timing and noise in response to estrogen. 顺式调节控制转录时间和噪音对雌激素的反应

Cell genomics Pub Date : 2024-05-08 Epub Date: 2024-04-24 DOI: 10.1016/j.xgen.2024.100542

Matthew Ginley-Hidinger, Hosiana Abewe, Kyle Osborne, Alexandra Richey, Noel Kitchen, Katelyn L Mortenson, Erin M Wissink, John Lis, Xiaoyang Zhang, Jason Gertz

{"title":"Cis-regulatory control of transcriptional timing and noise in response to estrogen.","authors":"Matthew Ginley-Hidinger, Hosiana Abewe, Kyle Osborne, Alexandra Richey, Noel Kitchen, Katelyn L Mortenson, Erin M Wissink, John Lis, Xiaoyang Zhang, Jason Gertz","doi":"10.1016/j.xgen.2024.100542","DOIUrl":"10.1016/j.xgen.2024.100542","url":null,"abstract":"Cis-regulatory elements control transcription levels, temporal dynamics, and cell-cell variation or transcriptional noise. However, the combination of regulatory features that control these different attributes is not fully understood. Here, we used single-cell RNA-seq during an estrogen treatment time course and machine learning to identify predictors of expression timing and noise. We found that genes with multiple active enhancers exhibit faster temporal responses. We verified this finding by showing that manipulation of enhancer activity changes the temporal response of estrogen target genes. Analysis of transcriptional noise uncovered a relationship between promoter and enhancer activity, with active promoters associated with low noise and active enhancers linked to high noise. Finally, we observed that co-expression across single cells is an emergent property associated with chromatin looping, timing, and noise. Overall, our results indicate a fundamental tradeoff between a gene's ability to quickly respond to incoming signals and maintain low variation across cells.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11099348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140871645","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

Blood-based epigenome-wide analyses of chronic low-grade inflammation across diverse population cohorts. 基于血液表观基因组的全人群慢性低度炎症分析。

Cell genomics Pub Date : 2024-05-08 Epub Date: 2024-04-30 DOI: 10.1016/j.xgen.2024.100544

Robert F Hillary, Hong Kiat Ng, Daniel L McCartney, Hannah R Elliott, Rosie M Walker, Archie Campbell, Felicia Huang, Kenan Direk, Paul Welsh, Naveed Sattar, Janie Corley, Caroline Hayward, Andrew M McIntosh, Cathie Sudlow, Kathryn L Evans, Simon R Cox, John C Chambers, Marie Loh, Caroline L Relton, Riccardo E Marioni, Paul D Yousefi, Matthew Suderman

{"title":"Blood-based epigenome-wide analyses of chronic low-grade inflammation across diverse population cohorts.","authors":"Robert F Hillary, Hong Kiat Ng, Daniel L McCartney, Hannah R Elliott, Rosie M Walker, Archie Campbell, Felicia Huang, Kenan Direk, Paul Welsh, Naveed Sattar, Janie Corley, Caroline Hayward, Andrew M McIntosh, Cathie Sudlow, Kathryn L Evans, Simon R Cox, John C Chambers, Marie Loh, Caroline L Relton, Riccardo E Marioni, Paul D Yousefi, Matthew Suderman","doi":"10.1016/j.xgen.2024.100544","DOIUrl":"10.1016/j.xgen.2024.100544","url":null,"abstract":"Chronic inflammation is a hallmark of age-related disease states. The effectiveness of inflammatory proteins including C-reactive protein (CRP) in assessing long-term inflammation is hindered by their phasic nature. DNA methylation (DNAm) signatures of CRP may act as more reliable markers of chronic inflammation. We show that inter-individual differences in DNAm capture 50% of the variance in circulating CRP (N = 17,936, Generation Scotland). We develop a series of DNAm predictors of CRP using state-of-the-art algorithms. An elastic-net-regression-based predictor outperformed competing methods and explained 18% of phenotypic variance in the Lothian Birth Cohort of 1936 (LBC1936) cohort, doubling that of existing DNAm predictors. DNAm predictors performed comparably in four additional test cohorts (Avon Longitudinal Study of Parents and Children, Health for Life in Singapore, Southall and Brent Revisited, and LBC1921), including for individuals of diverse genetic ancestry and different age groups. The best-performing predictor surpassed assay-measured CRP and a genetic score in its associations with 26 health outcomes. Our findings forge new avenues for assessing chronic low-grade inflammation in diverse populations.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11099341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140869007","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

Rare-variant association study unveils the Achilles' heel for HCC. 罕见变异关联研究揭示了 HCC 的致命弱点。

Cell genomics Pub Date : 2024-05-08 DOI: 10.1016/j.xgen.2024.100558

Yin Wang, Ying Wai Chan

引用次数: 0

The broken Alzheimer's disease genome. 破碎的阿尔茨海默病基因组

Cell genomics Pub Date : 2024-05-08 Epub Date: 2024-05-01 DOI: 10.1016/j.xgen.2024.100555

Cláudio Gouveia Roque, Hemali Phatnani, Ulrich Hengst

引用次数: 0