{"title":"Advancing methods for multi-ancestry genomics.","authors":"Lathan Liou, Christa Caggiano","doi":"10.1016/j.tig.2025.10.003","DOIUrl":"https://doi.org/10.1016/j.tig.2025.10.003","url":null,"abstract":"<p><p>Genomics research has historically been biased toward individuals of European ancestry, which has the potential to exacerbate health inequities (Martin, A.R. et al. Clinical use of current polygenic risk scores may exacerbate health disparities). To reduce these disparities, current efforts in human genetics emphasize the inclusion of diverse populations (All of Us Research Program Investigators, The 'All of Us' Research Program). Here, we highlight recent preprints that focus on the intricacies of researching participants with multiple genetic ancestries.</p>","PeriodicalId":54413,"journal":{"name":"Trends in Genetics","volume":" ","pages":""},"PeriodicalIF":16.3,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145309870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The histone code at a crossroads: history, context, and new approaches.","authors":"Julie Jung, Michael S Werner","doi":"10.1016/j.tig.2025.09.003","DOIUrl":"https://doi.org/10.1016/j.tig.2025.09.003","url":null,"abstract":"<p><p>Recent studies have reported that catalytically dead histone-modifying enzymes can rescue the function of their null alleles. Histone 'replacement' experiments have similarly found a lack of phenotypes for some modifications. Do these findings foretell a paradigm shift for the histone code hypothesis? Here, we discuss these results through the lens of ecology, evolution, and development ('eco-evo-devo') to provide context. We then highlight recent 'top-down' approaches, which start from environmentally influenced phenotypes and then attempt to identify causal mechanisms; placing function before molecule. Using this strategy, recent work in invertebrates has found key roles for histone acetylation and small RNAs in developmental plasticity. The synthesis of traditional 'bottom-up' with new 'top-down' approaches can resolve which molecules are epiphenomenal and which are truly epigenetic.</p>","PeriodicalId":54413,"journal":{"name":"Trends in Genetics","volume":" ","pages":""},"PeriodicalIF":16.3,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145294395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sequence-independent 6mA methyltransferases for epigenetic profiling and editing.","authors":"Jiachen Zhang, Yumiao Zhang, Jinghan Diao, Yifan Liu, Shan Gao","doi":"10.1016/j.tig.2025.09.002","DOIUrl":"https://doi.org/10.1016/j.tig.2025.09.002","url":null,"abstract":"<p><p>Gene activity is intricately shaped by its chromatin environment. Deciphering the chromatin landscape is essential for understanding the complex regulatory networks governing gene function. The newly re-recognized DNA N<sup>6</sup>-methyladenine (6mA) is relatively scarce in multicellular eukaryotes, which has facilitated the development of innovative chromatin profiling approaches employing sequence-independent 6mA methyltransferases (MTases) to introduce exogenous 6mA. In this review, we summarize recent advances in leveraging exogenous 6mA deposition and long-read sequencing in three major applications: chromatin landscape profiling, protein-DNA interaction mapping, and targeted epigenetic editing. For each, we outline representative workflows, highlight technical advantages, and discuss current challenges and prospects for optimization. Together, this review underscores the emerging power of exogenous 6mA as a versatile tool for decoding chromatin architecture and gene regulation.</p>","PeriodicalId":54413,"journal":{"name":"Trends in Genetics","volume":" ","pages":""},"PeriodicalIF":16.3,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christoph Bleidorn, Felicia Sandberg, Sebastian Martin, Alfried P Vogler, Lars Podsiadlowski
{"title":"The untapped potential of short-read sequencing in biodiversity research.","authors":"Christoph Bleidorn, Felicia Sandberg, Sebastian Martin, Alfried P Vogler, Lars Podsiadlowski","doi":"10.1016/j.tig.2025.09.001","DOIUrl":"https://doi.org/10.1016/j.tig.2025.09.001","url":null,"abstract":"<p><p>The power of short-read DNA sequencing in biodiversity research and evolutionary genomics is rapidly growing due to advances in technology and bioinformatics. Short-read sequencing offers powerful solutions for taxonomic identification, biomass estimation, and phylogenetic reconstruction. Moreover, short-read data enable robust estimation of genome size and repeat content, offering valuable insights into genome evolution. Though growing in popularity, long-read genome assemblies are often not feasible with material from museum collections or raw biodiversity samples. With the growing demand for DNA-based approaches in biodiversity research, short-read genomics provides an easily generated universal data source spanning all levels from individual genomes to ecosystems, and including all species on Earth, to achieve the objectives of the Global Biodiversity Framework (GBF) for the preservation of biodiversity.</p>","PeriodicalId":54413,"journal":{"name":"Trends in Genetics","volume":" ","pages":""},"PeriodicalIF":16.3,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Trends in GeneticsPub Date : 2025-10-01Epub Date: 2025-06-05DOI: 10.1016/j.tig.2025.05.005
Ruimin Xu, Yanhe Li, You Wu, Xiaoyu Liu, Shaorong Gao
{"title":"Epigenetic regulation in early embryo development: from zygotic genome activation to the first lineage specification.","authors":"Ruimin Xu, Yanhe Li, You Wu, Xiaoyu Liu, Shaorong Gao","doi":"10.1016/j.tig.2025.05.005","DOIUrl":"10.1016/j.tig.2025.05.005","url":null,"abstract":"<p><p>Epigenetic regulation plays a pivotal role in orchestrating early embryo development, guiding the transition from a totipotent zygote to a complex multicellular organism. This review summarizes the dynamic landscape of epigenetic reprogramming during preimplantation embryo development, emphasizing the interplay between DNA methylation, histone modifications, higher-order chromatin, transposable elements (TEs), and RNA modifications in resetting the parental epigenome. We also summarize the abnormal epigenetic reprogramming observed in somatic cell nuclear transfer (SCNT) and assisted reproductive technologies (ART), as well as clinical disorders resulting from these epigenetic defects, and discuss potential therapeutic strategies and future research directions. We seek to elucidate the role of epigenetic modifications in developmental defects, offering perspectives to enhance both developmental biology studies and clinical applications of assisted reproduction.</p>","PeriodicalId":54413,"journal":{"name":"Trends in Genetics","volume":" ","pages":"899-918"},"PeriodicalIF":16.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Trends in GeneticsPub Date : 2025-10-01Epub Date: 2025-08-04DOI: 10.1016/j.tig.2025.07.011
Ellen Frances Shute, Pavel Sinitcyn
{"title":"From reference to reality: identifying noncanonical peptides.","authors":"Ellen Frances Shute, Pavel Sinitcyn","doi":"10.1016/j.tig.2025.07.011","DOIUrl":"10.1016/j.tig.2025.07.011","url":null,"abstract":"<p><p>The translation of genome sequence variation into proteoform diversity lies at the heart of the central dogma. In a recent study, Zhu et al. developed a graph-based algorithm that models gene expression complexity, providing an exhaustive answer to the question: 'Given a set of genomic variants, which proteins might one see?'</p>","PeriodicalId":54413,"journal":{"name":"Trends in Genetics","volume":" ","pages":"851-852"},"PeriodicalIF":16.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144790760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Architectural RNAs: blueprints for functional membraneless organelle assembly.","authors":"Tetsuro Hirose, Naoko Fujiwara, Kensuke Ninomiya, Tetsuya Yamamoto, Shinichi Nakagawa, Tomohiro Yamazaki","doi":"10.1016/j.tig.2025.05.007","DOIUrl":"10.1016/j.tig.2025.05.007","url":null,"abstract":"<p><p>Among the pervasive transcripts from eukaryotic genomes, a novel subset, referred to as architectural RNAs (arcRNAs), has an essential role in assembling membraneless organelles (MLOs). These arcRNAs sequester specific RNA-binding proteins (RBPs) and promote phase separation through multivalent interactions. NEAT1_2, an archetypal arcRNA, serves as a blueprint for paraspeckle architecture, characterized by a shell-and-core micelle-like configuration and immiscibility with other MLOs, relying on the cooperative contributions of distinct modular RNA domains. arcRNAs regulate gene expression through three of MLO action modes (crucible, sponge, and hub), guided by the functional blueprints embedded in arcRNA sequences. Advanced high-throughput analyses have identified thousands of arcRNA candidates, underscoring their potential in organizing transient intracellular compartments and driving dynamic cellular processes.</p>","PeriodicalId":54413,"journal":{"name":"Trends in Genetics","volume":" ","pages":"919-933"},"PeriodicalIF":16.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Expanding horizons of CRISPR applications beyond genome editing.","authors":"Yu Liang, Shengkun Tong, Jingyu Zhang, Gao-Yi Tan, Lixin Zhang, Sang Yup Lee, Yaojun Tong","doi":"10.1016/j.tig.2025.06.003","DOIUrl":"10.1016/j.tig.2025.06.003","url":null,"abstract":"<p><p>Clustered regularly interspaced short palindromic repeats (CRISPR) technologies have rapidly evolved beyond genome editing, transforming fields such as molecular diagnostics, biosensing, transcriptional regulation, molecular imaging, protein interaction mapping, and single-cell analysis. Emerging CRISPR-based diagnostics harness the collateral cleavage activity of CRISPR-associated (Cas) enzymes for rapid nucleic acid detection. Advanced biosensors extend CRISPR's capabilities to detect ions, metabolites, and proteins by integrating synthetic biology components. Catalytically inactive Cas proteins enable precise gene regulation and live-cell imaging of nucleic acids, whereas CRISPR-guided proximity labeling has revolutionized the mapping of biomolecular interactions. Recent single-cell CRISPR screens provide unprecedented resolution of cellular heterogeneity. Future research will focus on overcoming current limitations. The integration of CRISPR technologies with artificial intelligence (AI), spatial omics, and microfluidics is expected to further amplify their impact.</p>","PeriodicalId":54413,"journal":{"name":"Trends in Genetics","volume":" ","pages":"934-953"},"PeriodicalIF":16.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Trends in GeneticsPub Date : 2025-10-01Epub Date: 2025-07-10DOI: 10.1016/j.tig.2025.06.013
Omar Matar, Ferdinand Marlétaz
{"title":"Animal origins: looping back in time.","authors":"Omar Matar, Ferdinand Marlétaz","doi":"10.1016/j.tig.2025.06.013","DOIUrl":"10.1016/j.tig.2025.06.013","url":null,"abstract":"<p><p>How did the chromatin folding mechanisms controlling gene regulation emerge during animal evolution? Kim et al. surveyed chromatin folding at high-resolution in unicellular relatives of animals as well as non-bilaterian animal lineages. They found that chromatin loops appeared concomitantly with complex gene regulation and uncovered an unexpected diversity of chromatin looping mechanisms.</p>","PeriodicalId":54413,"journal":{"name":"Trends in Genetics","volume":" ","pages":"849-850"},"PeriodicalIF":16.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Trends in GeneticsPub Date : 2025-10-01Epub Date: 2025-08-21DOI: 10.1016/j.tig.2025.07.007
Emma R James, Maliha Tasnim, Antoni Riera-Escamilla, Katinka Vigh-Conrad, Benjamin R Emery, Donald F Conrad, Kenneth I Aston
{"title":"Genetic and epigenetic landscape of male infertility.","authors":"Emma R James, Maliha Tasnim, Antoni Riera-Escamilla, Katinka Vigh-Conrad, Benjamin R Emery, Donald F Conrad, Kenneth I Aston","doi":"10.1016/j.tig.2025.07.007","DOIUrl":"10.1016/j.tig.2025.07.007","url":null,"abstract":"<p><p>Male infertility is a global health problem, affecting up to 6% of reproductive age men worldwide. It has an enormous personal and societal burden, along with public health implications beyond the inability to reproduce, including reduced future health and longevity. While the impact of infertility has long been appreciated, the molecular architecture of the disease is largely unknown. Nevertheless, the past decade has witnessed significant advances in our understanding of the molecular basis of male infertility. Here, we describe the contributions of genetic and epigenetic mechanisms to infertility-associated phenotypes and their impact beyond reproduction. This review focuses on progress in understanding defects in sperm production and function, and the potential impact of these advances on diagnosis, treatments, and improved health.</p>","PeriodicalId":54413,"journal":{"name":"Trends in Genetics","volume":" ","pages":"883-898"},"PeriodicalIF":16.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12419460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144978980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}