Cell genomics最新文献

{"title":"Genomic evolution shapes prostate cancer disease type.","authors":"Dan J Woodcock, Atef Sahli, Ruxandra Teslo, Vinayak Bhandari, Andreas J Gruber, Aleksandra Ziubroniewicz, Gunes Gundem, Yaobo Xu, Adam Butler, Ezequiel Anokian, Bernard J Pope, Chol-Hee Jung, Maxime Tarabichi, Stefan C Dentro, J Henry R Farmery, Peter Van Loo, Anne Y Warren, Vincent Gnanapragasam, Freddie C Hamdy, G Steven Bova, Christopher S Foster, David E Neal, Yong-Jie Lu, Zsofia Kote-Jarai, Michael Fraser, Robert G Bristow, Paul C Boutros, Anthony J Costello, Niall M Corcoran, Christopher M Hovens, Charlie E Massie, Andy G Lynch, Daniel S Brewer, Rosalind A Eeles, Colin S Cooper, David C Wedge","doi":"10.1016/j.xgen.2024.100511","DOIUrl":"10.1016/j.xgen.2024.100511","url":null,"abstract":"<p><p>The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Alternative evolutionary disease types. We therefore propose the evotype model for prostate cancer evolution wherein Alternative-evotype tumors diverge from those of the Canonical-evotype through the stochastic accumulation of genetic alterations associated with disruptions to androgen receptor DNA binding. Our model unifies many previous molecular observations, providing a powerful new framework to investigate prostate cancer disease progression.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10943594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013825","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":"Ancient genomes illuminate Eastern Arabian population history and adaptation against malaria.","authors":"Rui Martiniano, Marc Haber, Mohamed A Almarri, Valeria Mattiangeli, Mirte C M Kuijpers, Berenice Chamel, Emily M Breslin, Judith Littleton, Salman Almahari, Fatima Aloraifi, Daniel G Bradley, Pierre Lombard, Richard Durbin","doi":"10.1016/j.xgen.2024.100507","DOIUrl":"10.1016/j.xgen.2024.100507","url":null,"abstract":"<p><p>The harsh climate of Arabia has posed challenges in generating ancient DNA from the region, hindering the direct examination of ancient genomes for understanding the demographic processes that shaped Arabian populations. In this study, we report whole-genome sequence data obtained from four Tylos-period individuals from Bahrain. Their genetic ancestry can be modeled as a mixture of sources from ancient Anatolia, Levant, and Iran/Caucasus, with variation between individuals suggesting population heterogeneity in Bahrain before the onset of Islam. We identify the G6PD Mediterranean mutation associated with malaria resistance in three out of four ancient Bahraini samples and estimate that it rose in frequency in Eastern Arabia from 5 to 6 kya onward, around the time agriculture appeared in the region. Our study characterizes the genetic composition of ancient Arabians, shedding light on the population history of Bahrain and demonstrating the feasibility of studies of ancient DNA in the region.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10943591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139991988","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":"Integrative high-throughput enhancer surveying and functional verification divulges a YY2-condensed regulatory axis conferring risk for osteoporosis.","authors":"Xiao-Feng Chen, Yuan-Yuan Duan, Ying-Ying Jia, Qian-Hua Dong, Wei Shi, Yan Zhang, Shan-Shan Dong, Meng Li, Zhongbo Liu, Fei Chen, Xiao-Ting Huang, Ruo-Han Hao, Dong-Li Zhu, Rui-Hua Jing, Yan Guo, Tie-Lin Yang","doi":"10.1016/j.xgen.2024.100501","DOIUrl":"10.1016/j.xgen.2024.100501","url":null,"abstract":"<p><p>The precise roles of chromatin organization at osteoporosis risk loci remain largely elusive. Here, we combined chromatin interaction conformation (Hi-C) profiling and self-transcribing active regulatory region sequencing (STARR-seq) to qualify enhancer activities of prioritized osteoporosis-associated single-nucleotide polymorphisms (SNPs). We identified 319 SNPs with biased allelic enhancer activity effect (baaSNPs) that linked to hundreds of candidate target genes through chromatin interactions across 146 loci. Functional characterizations revealed active epigenetic enrichment for baaSNPs and prevailing osteoporosis-relevant regulatory roles for their chromatin interaction genes. Further motif enrichment and network mapping prioritized several putative, key transcription factors (TFs) controlling osteoporosis binding to baaSNPs. Specifically, we selected one top-ranked TF and deciphered that an intronic baaSNP (rs11202530) could allele-preferentially bind to YY2 to augment PAPSS2 expression through chromatin interactions and promote osteoblast differentiation. Our results underline the roles of TF-mediated enhancer-promoter contacts for osteoporosis, which may help to better understand the intricate molecular regulatory mechanisms underlying osteoporosis risk loci.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10943593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713485","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":"Genome-wide classification of epigenetic activity reveals regions of enriched heritability in immune-related traits.","authors":"Miriam Stricker, Weijiao Zhang, Wei-Yi Cheng, Steven Gazal, Calliope Dendrou, Satu Nahkuri, Pier Francesco Palamara","doi":"10.1016/j.xgen.2024.100508","DOIUrl":"10.1016/j.xgen.2024.100508","url":null,"abstract":"","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10943573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133407","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":"The Mutographs biorepository: A unique genomic resource to study cancer around the world.","authors":"Sandra Perdomo, Behnoush Abedi-Ardekani, Ana Carolina de Carvalho, Aida Ferreiro-Iglesias, Valérie Gaborieau, Thomas Cattiaux, Hélène Renard, Priscilia Chopard, Christine Carreira, Andreea Spanu, Arash Nikmanesh, Ricardo Cortez Cardoso Penha, Samuel O Antwi, Patricia Ashton-Prolla, Cristina Canova, Taned Chitapanarux, Riley Cox, Maria Paula Curado, José Carlos de Oliveira, Charles Dzamalala, Elenora Fabianova, Lorenzo Ferri, Rebecca Fitzgerald, Lenka Foretova, Steven Gallinger, Alisa M Goldstein, Ivana Holcatova, Antonio Huertas, Vladimir Janout, Sonata Jarmalaite, Radka Kaneva, Luiz Paulo Kowalski, Tomislav Kulis, Pagona Lagiou, Jolanta Lissowska, Reza Malekzadeh, Dana Mates, Valerie McCorrmack, Diana Menya, Sharayu Mhatre, Blandina Theophil Mmbaga, André de Moricz, Péter Nyirády, Miodrag Ognjanovic, Kyriaki Papadopoulou, Jerry Polesel, Mark P Purdue, Stefan Rascu, Lidia Maria Rebolho Batista, Rui Manuel Reis, Luis Felipe Ribeiro Pinto, Paula A Rodríguez-Urrego, Surasak Sangkhathat, Suleeporn Sangrajrang, Tatsuhiro Shibata, Eduard Stakhovsky, Beata Świątkowska, Carlos Vaccaro, Jose Roberto Vasconcelos de Podesta, Naveen S Vasudev, Marta Vilensky, Jonathan Yeung, David Zaridze, Kazem Zendehdel, Ghislaine Scelo, Estelle Chanudet, Jingwei Wang, Stephen Fitzgerald, Calli Latimer, Sarah Moody, Laura Humphreys, Ludmil B Alexandrov, Michael R Stratton, Paul Brennan","doi":"10.1016/j.xgen.2024.100500","DOIUrl":"10.1016/j.xgen.2024.100500","url":null,"abstract":"<p><p>Large-scale biorepositories and databases are essential to generate equitable, effective, and sustainable advances in cancer prevention, early detection, cancer therapy, cancer care, and surveillance. The Mutographs project has created a large genomic dataset and biorepository of over 7,800 cancer cases from 30 countries across five continents with extensive demographic, lifestyle, environmental, and clinical information. Whole-genome sequencing is being finalized for over 4,000 cases, with the primary goal of understanding the causes of cancer at eight anatomic sites. Genomic, exposure, and clinical data will be publicly available through the International Cancer Genome Consortium Accelerating Research in Genomic Oncology platform. The Mutographs sample and metadata biorepository constitutes a legacy resource for new projects and collaborations aiming to increase our current research efforts in cancer genomic epidemiology globally.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10943582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139704151","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":"Haplotype-specific assembly of shattered chromosomes in esophageal adenocarcinomas.","authors":"Jannat Ijaz, Edward Harry, Keiran Raine, Andrew Menzies, Kathryn Beal, Michael A Quail, Sonia Zumalave, Hyunchul Jung, Tim H H Coorens, Andrew R J Lawson, Daniel Leongamornlert, Hayley E Francies, Mathew J Garnett, Zemin Ning, Peter J Campbell","doi":"10.1016/j.xgen.2023.100484","DOIUrl":"10.1016/j.xgen.2023.100484","url":null,"abstract":"<p><p>The epigenetic landscape of cancer is regulated by many factors, but primarily it derives from the underlying genome sequence. Chromothripsis is a catastrophic localized genome shattering event that drives, and often initiates, cancer evolution. We characterized five esophageal adenocarcinoma organoids with chromothripsis using long-read sequencing and transcriptome and epigenome profiling. Complex structural variation and subclonal variants meant that haplotype-aware de novo methods were required to generate contiguous cancer genome assemblies. Chromosomes were assembled separately and scaffolded using haplotype-resolved Hi-C reads, producing accurate assemblies even with up to 900 structural rearrangements. There were widespread differences between the chromothriptic and wild-type copies of chromosomes in topologically associated domains, chromatin accessibility, histone modifications, and gene expression. Differential epigenome peaks were most enriched within 10 kb of chromothriptic structural variants. Alterations in transcriptome and higher-order chromosome organization frequently occurred near differential epigenetic marks. Overall, chromothripsis reshapes gene regulation, causing coordinated changes in epigenetic landscape, transcription, and chromosome conformation.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10879010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139486559","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":"Identification of a regulatory pathway governing TRAF1 via an arthritis-associated non-coding variant.","authors":"Qiang Wang, Marta Martínez-Bonet, Taehyeung Kim, Jeffrey A Sparks, Kazuyoshi Ishigaki, Xiaoting Chen, Marc Sudman, Vitor Aguiar, Sangwan Sim, Marcos Chiñas Hernandez, Darren J Chiu, Alexandra Wactor, Brian Wauford, Miranda C Marion, Maria Gutierrez-Arcelus, John Bowes, Stephen Eyre, Ellen Nordal, Sampath Prahalad, Marite Rygg, Vibeke Videm, Soumya Raychaudhuri, Matthew T Weirauch, Carl D Langefeld, Susan D Thompson, Peter A Nigrovic","doi":"10.1016/j.xgen.2024.100502","DOIUrl":"10.1016/j.xgen.2024.100502","url":null,"abstract":"","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10879129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742846","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":"Locus-level L1 DNA methylation profiling reveals the epigenetic and transcriptional interplay between L1s and their integration sites.","authors":"Sophie Lanciano, Claude Philippe, Arpita Sarkar, David Pratella, Cécilia Domrane, Aurélien J Doucet, Dominic van Essen, Simona Saccani, Laure Ferry, Pierre-Antoine Defossez, Gael Cristofari","doi":"10.1016/j.xgen.2024.100498","DOIUrl":"10.1016/j.xgen.2024.100498","url":null,"abstract":"<p><p>Long interspersed element 1 (L1) retrotransposons are implicated in human disease and evolution. Their global activity is repressed by DNA methylation, but deciphering the regulation of individual copies has been challenging. Here, we combine short- and long-read sequencing to unveil L1 methylation heterogeneity across cell types, families, and individual loci and elucidate key principles involved. We find that the youngest primate L1 families are specifically hypomethylated in pluripotent stem cells and the placenta but not in most tumors. Locally, intronic L1 methylation is intimately associated with gene transcription. Conversely, the L1 methylation state can propagate to the proximal region up to 300 bp. This phenomenon is accompanied by the binding of specific transcription factors, which drive the expression of L1 and chimeric transcripts. Finally, L1 hypomethylation alone is typically insufficient to trigger L1 expression due to redundant silencing pathways. Our results illuminate the epigenetic and transcriptional interplay between retrotransposons and their host genome.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10879037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139681977","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":"Phylogenomic analyses unraveled the evolution of viral tolerance in bats.","authors":"Yulong Xie, Guojie Zhang","doi":"10.1016/j.xgen.2024.100503","DOIUrl":"10.1016/j.xgen.2024.100503","url":null,"abstract":"<p><p>Bats host a range of viruses, exhibiting a coevolution process with many virus genera and a special capacity for viral tolerance. Foley et al.¹ performed phylogenomic analyses for 60 bat species, finding that swarming behavior might facilitate cross-species introgression and the spread of anti-virus immunity gene loci across species.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10879121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742847","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":"Better translation via collaboration: The MRC National Mouse Genetics Network.","authors":"Owen Sansom, Sara Wells, David Kent, Andrew Wood, Robert D S Pitceathly, Anthony Isles, Karen Liu, Stephen Twigg, Karen Blyth, Louis Chesler","doi":"10.1016/j.xgen.2023.100483","DOIUrl":"10.1016/j.xgen.2023.100483","url":null,"abstract":"<p><p>The MRC National Mouse Genetics Network (NMGN) has been established in the UK to bring together researchers from academia and industry across the country from a wide range of disease areas and research backgrounds to rapidly facilitate clinical translation of mouse research findings and foster an environment of interdisciplinary learning.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10879024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742844","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}