Genome Biology最新文献

{"title":"Codon-specific ribosome stalling reshapes translational dynamics during branched-chain amino acid starvation","authors":"Lina Worpenberg, Cédric Gobet, Felix Naef","doi":"10.1186/s13059-025-03800-6","DOIUrl":"https://doi.org/10.1186/s13059-025-03800-6","url":null,"abstract":"Cells regulate protein synthesis in response to fluctuating nutrient availability through mechanisms that affect both translation initiation and elongation. Branched-chain amino acids, leucine, isoleucine, and valine, are essential nutrients. However, how their depletion affects translation remains largely unclear. Here, we investigate the immediate effects of single, double, and triple branched-chain amino acid deprivation on translational dynamics in NIH3T3 cells using RNA-seq and ribosome profiling. All starvation conditions increased ribosome dwell times, with pronounced stalling at all valine codons during valine and triple starvation, whereas leucine and isoleucine starvation produced milder, codon-specific effects. Notably, stalling under isoleucine deprivation largely decreased under triple starvation. Positional enrichment of valine codons near the 5′ end and downstream isoleucine codons potentially contributes to these patterns, suggesting a possible elongation bottleneck that influences translational responses under branched-chain amino acid starvation. The presence of multiple valine stalling sites was associated with decreased protein levels. Finally, codon-specific dwell time changes correlated strongly with patterns of tRNA isoacceptor charging. Together, these findings suggest that differential ribosome stalling under branched-chain amino acid starvation reflects a balance between amino acid supply, tRNA charging dynamics, codon position, and stress-response signaling.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"16 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning and statistical inference in microbial population genomics","authors":"Samuel K. Sheppard, Nicolas Arning, David W. Eyre, Daniel J. Wilson","doi":"10.1186/s13059-025-03775-4","DOIUrl":"https://doi.org/10.1186/s13059-025-03775-4","url":null,"abstract":"The availability of large genome datasets has changed the microbiology research landscape. Analyzing such data requires computationally demanding analyses, and new approaches have come from different data analysis philosophies. Machine learning and statistical inference have overlapping knowledge discovery aims and approaches. However, machine learning focuses on optimizing prediction, whereas statistical inference focuses on understanding the processes relating variables. In this review, we outline the different aspirations, precepts, and resulting methodologies, with examples from microbial genomics. Emphasizing complementarity, we argue that the combination and synthesis of machine learning and statistics has potential for pathogen research in the big data era.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"1 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hybrid BAG-seq: DNA and RNA from the same single nucleus reveals interactions between genomic and transcriptomic landscapes in human tumor samples","authors":"Siran Li, Joan Alexander, Jude Kendall, Peter Andrews, Elizabeth Rose, Hope Orjuela, Sarah Park, Craig Podszus, Liam Shanley, Nissim Ranade, Patrick Morris, Danielle Stauder, Daniel Bradford, Zachary Laster, Michael Ronemus, Arvind Rishi, Marina Frimer, Rong Ma, David L. Donoho, Gary L. Goldberg, Michael Wigler, Dan Levy","doi":"10.1186/s13059-025-03790-5","DOIUrl":"https://doi.org/10.1186/s13059-025-03790-5","url":null,"abstract":"We introduce hybrid BAG-seq: a high-throughput, multi-omic method that simultaneously captures DNA and RNA from single nuclei. We apply this protocol to 65,499 single nuclei from samples of five uterine cancer patients and validate the clustering using RNA-only and DNA-only protocols from the same tissues. Multiple tumor genome or expression clusters are often present within a patient, with different tumor clones projecting into distinct or shared expression states, demonstrating nearly all possible genome-transcriptome correlations. We also identify mutant stroma with significant X chromosome loss in various cell types and patient-specific stromal subtypes exhibiting aberrant expression patterns.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"15 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-resolution genome assembly reveals retrotransposon-mediated centromere dynamics in rye","authors":"Congyang Yi, Qian Liu, Congle Zhu, Chang Liu, Chen Zhou, Wanna He, Chunhui Wang, Jing Yuan, Yang Liu, Fangpu Han","doi":"10.1186/s13059-025-03792-3","DOIUrl":"https://doi.org/10.1186/s13059-025-03792-3","url":null,"abstract":"The genome of rye, Secale cereale, is distinguished by large repetitive regions including subtelomeric heterochromatin and retrotransposon-dominant centromeres, which contrast with the satellite-repeat-based centromeres in most characterized plant genome assemblies. This study aims to decode the architecture and evolution of these elusive regions through high-resolution genome assembly, with a focus on centromere dynamics and chromatin regulation. Using PacBio HiFi and Nanopore sequencing, we generate a chromosome-scale assembly encompassing three complete centromeres and resolving subtelomeric heterochromatin. We identify terminal tandem repeat arrays as key determinants in establishing specialized chromatin environments linked to retrotransposon deposition. Notably, rye centromeres exhibit an unconventional epigenetic signature depleted of conventional activation and repression marks but displaying unique DNA hypomethylation patterns. This retrotransposon-enriched landscape promotes both the integration of young LTR retrotransposons and the recruitment of CENH3. Cross-species CENH3 ChIP-seq analyses reveal that Cereba retrotransposons are associated with enhanced CENH3 loading in cultivated and wild rye lineages, particularly through their conserved protease and integrase domains, suggesting a potential positive feedback loop for centromere evolution. Our findings establish retrotransposons as autonomous organizers of centromere chromatin and identity in rye, challenging the paradigm of satellite-dependent centromere specification. The dual role of retrotransposons in maintaining CENH3 recruitment while facilitating genomic innovation provides a mechanistic basis for centromere plasticity. This work advances functional genomics of Triticeae crops and opens new avenues for centromere engineering to manipulate meiotic stability and chromosome transmission in crop breeding.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"21 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145141385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential regulation of mesoscale chromosome conformations in osteoblasts and osteosarcoma","authors":"Madhoolika Bisht, Yu-Chieh Chung, Siou-Luan He, Sydney Willey, Benjamin D. Sunkel, Meng Wang, Benjamin Z. Stanton, Li-Chun Tu","doi":"10.1186/s13059-025-03785-2","DOIUrl":"https://doi.org/10.1186/s13059-025-03785-2","url":null,"abstract":"Chromosome conformation within the nucleus is essential for genome function. These have primarily been studied at the scale of loops and compartments, or at lower spatial resolution using traditional in situ hybridization in chemically fixed samples. However, the mesoscale organization of single chromosomes in vivo, shaped by the interplay between chromatin architectural proteins and histone modifications, remains partially understood. In this study, we interrogated the mesoscale conformations of interphase chromosomes in live human osteoblasts and transformed osteosarcoma cells, focusing on chromosome 19. Chromosome conformations were quantified by the aspect ratio of the principal axes of gyration tensors. In osteoblasts, approximately 81% of chromosome 19 are observed to consist of regions characterized by highly extended organizations, with aspect ratios approximately four times greater than those of spheres. In contrast, in osteosarcoma cells, the chromosome displays an extensively collapsed conformation, with aspect ratios more closely approximately that of a sphere. In both cell types, the chromosome’s conformation is bimodal and the balance between these two modes differs very significantly between the two cell types. While the mesoscopic conformation is considerably stable, it is superimposed on dynamic, smaller scale regions. Additional results reveal that this significant conformational shift is independent of the cell cycle but co-regulated by CTCF, cohesion, and H3K27 modifications. Our findings provide new insights into the coordinated complex regulatory mechanisms governing mesoscale chromosome organization in normal and transformed osteogenic tissues.\u0000","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"2 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145141409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction of plant-derived metabolites and rhizobiome functions enhances drought stress tolerance","authors":"Anna Kazarina, Soumyadev Sarkar, Bryttan Adams, Brooke Vogt, Leslie Rodela, Sophia Pogranichny, Summer Powell, Hallie Wiechman, Leah Heeren, Nicholas Reese, Darcy Thompson, Qinghong Ran, Eli Hartung, Alina Akhunova, Eduard Akhunov, Loretta Johnson, Ari Jumpponen, Sonny T.M. Lee","doi":"10.1186/s13059-025-03778-1","DOIUrl":"https://doi.org/10.1186/s13059-025-03778-1","url":null,"abstract":"Plants have evolved alongside microbes, enabling plants to better cope with abiotic and biotic stress. Interactions between plant roots and local soil microbes are critical for environmental adaptation and plant health. Plants actively regulate the microbial community composition in their rhizospheres to recruit specific microorganisms that enhance their fitness in the ecosystem they inhabit. This study builds on prior research suggesting that plants exhibit a “home field advantage” by preferentially recruiting microbes unique to their native environments, likely through mutual recognition and selective recruitment mechanisms. Using gene- and genome-centric approaches, we assess the functional potential of root-associated microbes and profile their host metabolites to uncover the metabolic outputs potentially regulating host‒microbe interactions in Andropogon gerardii. We find that plants adapted to drier environments experience less stress, producing fewer stress-related metabolites and impacting the recruitment of microbes with genes linked to stress relief pathways. In particular, plant-derived trimethyllysine is highly associated with microbial populations capable of improving nutrient uptake, producing plant growth-promoting compounds, and modulating stress responses. This study highlights the critical interplay between host exudates and microbial substrate uptake as the primary mechanism of rhizosphere assembly. We demonstrate that plants actively produce metabolites to recruit microbial populations with the functional potential to enhance their ability to thrive in stressful environments. This research provides insights into the mechanisms of plant–microbe communication, rhizosphere recruitment, and the complex interplay of plant–microbe interactions. Furthermore, it highlights promising avenues for manipulating rhizosphere microbiomes to support conservation agriculture when coping with climate change.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"17 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145141466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-nucleus transcriptomics revealed auxin-driven mechanisms of wood plasticity to enhance severe drought tolerance in poplar","authors":"Daniela Gómez-Soto, Wendell J. Pereira, Alejandro Piedrabuena-Díaz, Christopher Dervinis, Matias Kirst, Isabel Allona, Mariano Perales, Daniel Conde","doi":"10.1186/s13059-025-03794-1","DOIUrl":"https://doi.org/10.1186/s13059-025-03794-1","url":null,"abstract":"Drought significantly affects forests and woody crops by limiting their growth, increasing their susceptibility to diseases, and reducing productivity. Wood anatomical plasticity is a crucial adaptive mechanism that enables trees to cope with fluctuations in water availability. During severe drought, trees develop more and narrower vessels, enhancing hydraulic safety and reducing the risk of embolism. However, the molecular regulation of vessel formation is still not well understood. Using single-nucleus transcriptomics, we have generated a cell type-specific gene expression map of the mature poplar stem under well-watered and drought conditions. Our findings reveal extensive gene expression reprogramming in xylem-forming cells, with changes in auxin homeostasis identified as a key mechanism for anatomical adaptation. Specifically, we show that poplar WAT1-like genes control vessel spatial patterning. Additionally, the downregulation of WAT1-like gene expression in the dividing cells of the vascular cambium and the upregulation of MP-like gene expression in cells undergoing early vessel differentiation facilitate the formation of secondary xylem with narrower and more numerous vessels under drought. Furthermore, the wat2 mutant exhibits greater drought tolerance than wild-type trees, underscoring its potential for developing drought-resilient tree varieties. This study provides the first single-nucleus transcriptomic map of hybrid poplar stems under severe drought, uncovering auxin-driven hormonal networks that regulate xylem plasticity and enhance drought tolerance. These insights provide valuable targets for improving resilience in poplar and other woody species.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"2 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145141471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome of the green-head ant, Rhytidoponera metallica, reveals mechanisms of toxin evolution in a genetically hyper-diverse eusocial species","authors":"Anders Isaksen, Pedro G. Nachtigall, Robin A. Araya, Jia Hao Beh, Samuel D. Robinson, Thomas F. Hansen, Eivind A. B. Undheim","doi":"10.1186/s13059-025-03777-2","DOIUrl":"https://doi.org/10.1186/s13059-025-03777-2","url":null,"abstract":"While ants are textbook examples of eusocial animals in which altruistic behavior is maintained through kin selection, several ants form genetically diverse colonies that challenge this concept. One example is the Australian green-head ant (Rhytidoponera metallica) whose colonies harbor such extreme genetic variation that they have been speculated to represent an unstable form of eusociality. Yet, R. metallica is among the most successful ants on the Australian subcontinent. This success has been hypothesized to be partly due to the diverse venoms harbored within each colony. However, the genomic basis and evolutionary scenarios that maintain this toxin diversity remain unknown. To examine toxin genomic architecture, quantify individual-level genetic variation, and identify both proximate and ultimate mechanisms that have facilitated the toxin diversity in R. metallica, we generate a high-quality draft genome from a single worker. Most ectatotoxin genes are in clusters that contain evidence of multiple, complex gene-family expansions, some of which are likely explained by the presence of transposable elements. We also show that toxin regions of the genome exhibit elevated genetic variation despite being under strong selection and that this variation can translate to phenotypic diversity through toxin alleles with different functional properties. Taken together, our results point to classical gene duplication and diversification as the main evolutionary mechanism by which the main toxin family in ant venoms evolves, suggest toxin-gene functional diversification under frequency-dependent selection maintains colony-level venom hypervariability in R. metallica, and provide new insight into the role of multi-level selection in eusocial animals.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"62 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145141386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering functional landscapes of rumen microbiota unveils the role of Prevotella bryantii in milk fat synthesis in goats","authors":"Yu Lei, Yining Zheng, Yiting Yan, Kai Zhang, Xuyang Sun, Bo Yang, Lan Ge, Zhongming Meng, Xi Cao, Xiumin Zhang, Xiaoting Yan, Yangbin Xu, Ting Zhang, Jinping Shi, Shiwei Chen, Qiang Qiu, Yulin Chen, Lu Deng, Zhipeng Li, Xiaolong Wang, Ke Zhang","doi":"10.1186/s13059-025-03788-z","DOIUrl":"https://doi.org/10.1186/s13059-025-03788-z","url":null,"abstract":"The rumen microbiome is critical for regulating milk synthesis in dairy livestock, yet the molecular mechanisms linking microbial functions to host lipid metabolism remain poorly understood. While host genetics and microbial composition have been studied, integrative analyses of the rumen-blood-mammary gland axis remain lacking. Here, we present the goat rumen microbial reference gene catalog and 5514 metagenome-assembled genomes (MAGs) from 160 multi-breed rumen samples. Integrating this resource with lactation data from 177 Saanen dairy goats, we identify Prevotella spp. as keystone taxa driving concurrent increases in milk yield and fat percentage. Functional and metabolomic profiling reveals that Prevotella bryantii B14 synthesizes nicotinate, which is converted to nicotinamide in circulation. Using in vitro and in vivo models, we demonstrate that nicotinamide activates the mTORC1 pathway in mammary epithelial cells via GPR109A, which upregulates transcription factors SREBP and PPAR-γ and the downstream lipogenic genes FASN, ACCα, and SCD1 to promote milk fat synthesis. In contrast, the relative deficiency of P. bryantii B14 and the associated reduction in nicotinamide levels in the rumen of poor lactating dairy goats may represent a significant contributor to impaired lactation performance. Additionally, the enhanced hydrogenotrophic methanogenesis activity may also adversely affect their lactation phenotype. Our study establishes a causal link between rumen microbial metabolism and mammary lipid synthesis mediated by nicotinamide-mTORC1 signaling and identifies Prevotella abundance as a biomarker for precision breeding. These findings advance the understanding of microbiome-host crosstalk in lactation and provide actionable strategies for enhancing dairy productivity through microbiota-targeted interventions.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"18 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145141384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SNPmanifold: detecting single-cell clonality and lineages from single-nucleotide variants using binomial variational autoencoder","authors":"Hoi Man Chung, Yuanhua Huang","doi":"10.1186/s13059-025-03803-3","DOIUrl":"https://doi.org/10.1186/s13059-025-03803-3","url":null,"abstract":"Single-nucleotide-variant (SNV) clone assignment of high-covariance single-cell lineage tracing data remains a challenge due to hierarchical mutation structure and many missing signals. We develop SNPmanifold, a Python package that learns an SNV embedding manifold using a binomial variational autoencoder to give an efficient and interpretable cell-cell distance metric. We demonstrate that SNPmanifold is a suitable tool for analysis of complex, single-cell SNV mutation data, such as in the context of demultiplexing a large number of donors and somatic lineage tracing via mitochondrial SNV data and can reveal insights into single-cell clonality and lineages more accurately and comprehensively than existing methods.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"73 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145141465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}