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High-resolution time-series transcriptomic and metabolomic profiling reveals the regulatory mechanism underlying salt tolerance in maize 高分辨率时间序列转录组学和代谢组学分析揭示了玉米耐盐性的调控机制
IF 12.3 1区 生物学
Genome Biology Pub Date : 2025-09-10 DOI: 10.1186/s13059-025-03766-5
Fei Zhang, Boming Ji, Si Wu, Jie Zhang, Hui Zhang, Fei Wang, Baoxing Song, Qing Sang, Wenjie Huang, Shijuan Yan, Mustafa Bulut, Yariv Brotman, Mingqiu Dai
{"title":"High-resolution time-series transcriptomic and metabolomic profiling reveals the regulatory mechanism underlying salt tolerance in maize","authors":"Fei Zhang, Boming Ji, Si Wu, Jie Zhang, Hui Zhang, Fei Wang, Baoxing Song, Qing Sang, Wenjie Huang, Shijuan Yan, Mustafa Bulut, Yariv Brotman, Mingqiu Dai","doi":"10.1186/s13059-025-03766-5","DOIUrl":"https://doi.org/10.1186/s13059-025-03766-5","url":null,"abstract":"Soil salinization represents a critical global challenge to agricultural productivity, profoundly impacting crop yields and threatening food security. Plant salt-responsive is complex and dynamic, making it challenging to fully elucidate salt tolerance mechanism and leading to gaps in our understanding of how plants adapt to and mitigate salt stress. Here, we conduct high-resolution time-series transcriptomic and metabolomic profiling of the extremely salt-tolerant maize inbred line, HLZY, and the salt-sensitive elite line, JI853. Utilizing advanced data mining techniques, we identify key factors underlying the divergence in salt tolerance between these two lines and discover a series of novel genes and metabolites essential for maize salt tolerance. Additionally, we develop an innovative decision algorithm that enabled the construction of a high-confidence gene regulatory network for important salt-responsive metabolites. Comprehensive genetic and molecular studies further reveal the pivotal role of a hub gene, ZmGLN2, in regulating metabolite biosynthesis and salt tolerance in maize. Our study provides the first high-resolution transcriptomic and metabolomic dataset for crop salt response, uncovering novel maize salt-responsive genes and metabolites. These findings demonstrate the effectiveness of high-resolution multi-omics in deciphering the mechanisms underlying complex crop traits. Furthermore, we develop a systematic analytical framework for mining time-series multi-omics data, which can be broadly applied to other species or traits.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"56 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025699","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}
引用次数: 0
The systematic assessment of completeness of public metadata accompanying omics studies in the Gene Expression Omnibus data repository 基因表达综合数据库中伴随组学研究的公共元数据完整性的系统评估
IF 12.3 1区 生物学
Genome Biology Pub Date : 2025-09-09 DOI: 10.1186/s13059-025-03725-0
Yu-Ning Huang, Pooja Vinod Jaiswal, Anushka Rajes, Anushka Yadav, Dottie Yu, Fangyun Liu, Grace Scheg, Emma Shih, Grigore Boldirev, Irina Nakashidze, Aditya Sarkar, Jay Himanshu Mehta, Ke Wang, Khooshbu Kantibhai Patel, Mustafa Ali Baig Mirza, Kunali Chetan Hapani, Qiushi Peng, Ram Ayyala, Ruiwei Guo, Shaunak Kapur, Tejasvene Ramesh, Dumitru Ciorbă, Viorel Munteanu, Viorel Bostan, Mihai Dimian, Malak S. Abedalthagafi, Serghei Mangul
{"title":"The systematic assessment of completeness of public metadata accompanying omics studies in the Gene Expression Omnibus data repository","authors":"Yu-Ning Huang, Pooja Vinod Jaiswal, Anushka Rajes, Anushka Yadav, Dottie Yu, Fangyun Liu, Grace Scheg, Emma Shih, Grigore Boldirev, Irina Nakashidze, Aditya Sarkar, Jay Himanshu Mehta, Ke Wang, Khooshbu Kantibhai Patel, Mustafa Ali Baig Mirza, Kunali Chetan Hapani, Qiushi Peng, Ram Ayyala, Ruiwei Guo, Shaunak Kapur, Tejasvene Ramesh, Dumitru Ciorbă, Viorel Munteanu, Viorel Bostan, Mihai Dimian, Malak S. Abedalthagafi, Serghei Mangul","doi":"10.1186/s13059-025-03725-0","DOIUrl":"https://doi.org/10.1186/s13059-025-03725-0","url":null,"abstract":"Recent advances in high-throughput sequencing technologies have enabled the collection and sharing of a massive amount of omics data, along with its associated metadata—descriptive information that contextualizes the data, including phenotypic traits and experimental design. Enhancing metadata availability is critical to ensure data reusability and reproducibility and to facilitate novel biomedical discoveries through effective data reuse. Yet, incomplete metadata accompanying public omics data may hinder reproducibility and reusability and limit secondary analyses. Our study assesses the completeness of metadata in over 253 scientific studies, covering more than 164,000 samples from both human and non-human mammalian studies. We find that over 25% of critical metadata are omitted, with only 74.8% of relevant phenotypes available in publications or public repositories. Notably, public repositories alone contain 62% of the phenotypes, surpassing the textual content of publications by 3.5%. Only 11.5% of studies completely shared all phenotypes, while 37.9% shared less than 40% of the phenotypes. Additionally, studies with non-human samples are more likely to include complete metadata compared to human studies. Similar trends are observed in an extended dataset comprising 61,000 studies and 2.1 million samples from the Gene Expression Omnibus (GEO) data repository. These findings highlight significant gaps in metadata sharing, underscoring the need for standardized practices to improve metadata availability. Enhanced metadata reporting would foster data reusability, support better-informed decision-making, and promote reproducible research across the biomedical field.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"44 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017452","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}
引用次数: 0
Distinct evolutionary trajectories of subgenomic centromeres in polyploid wheat 多倍体小麦亚基因组着丝粒的不同进化轨迹
IF 12.3 1区 生物学
Genome Biology Pub Date : 2025-09-09 DOI: 10.1186/s13059-025-03759-4
Yuhong Huang, Yang Liu, Chang Liu, Congyang Yi, Jinsheng Lai, Hongqing Ling, Handong Su, Fangpu Han
{"title":"Distinct evolutionary trajectories of subgenomic centromeres in polyploid wheat","authors":"Yuhong Huang, Yang Liu, Chang Liu, Congyang Yi, Jinsheng Lai, Hongqing Ling, Handong Su, Fangpu Han","doi":"10.1186/s13059-025-03759-4","DOIUrl":"https://doi.org/10.1186/s13059-025-03759-4","url":null,"abstract":"Centromeres are crucial for precise chromosome segregation and maintaining genome stability during cell division. However, their evolutionary dynamics, particularly in polyploid organisms with complex genomic architectures, remain largely enigmatic. Allopolyploid wheat, with its well-defined hierarchical ploidy series and recent polyploidization history, serves as an excellent model to explore centromere evolution. In this study, we perform a systematic comparative analysis of centromeres in common wheat and its corresponding ancestral species, utilizing the latest comprehensive reference genome assembly available. Our findings reveal that wheat centromeres predominantly consist of five types of centromeric-specific retrotransposon elements (CRWs), with CRW1 and CRW2 being the most prevalent. We identify distinct evolutionary trajectories in the functional centromeres of each subgenome, characterized by variations in copy number, insertion age, and CRW composition. By utilizing CENH3-ChIP data across various ploidy levels, we uncover a series of CRW invasion events that have shaped the evolution of AA subgenome centromeres. Conversely, the evolutionary process of the DD subgenome centromeres involves their expansion from diploid to hexaploid wheat, facilitating adaptation to a larger genomic context. Integration of complete einkorn centromere assemblies and Aegilops tauschii pan-genomes further revealed subgenome-specific centromere evolutionary trajectories. By inclusion of synthetic hexaploid from S2-S3 generations, alongside 2x/6 × natural accessions, we demonstrate that DD subgenome centromere expansion represents a gradual evolutionary process rather than an immediate response to polyploidization. Our study provides a comprehensive landscape of centromere adaptation, evolution, and maturation, along with insights into how retrotransposon invasions drive centromere evolution in polyploid wheat.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"38 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017493","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}
引用次数: 0
Bacillus drives functional states in synthetic plant root bacterial communities 芽孢杆菌驱动合成植物根系细菌群落的功能状态
IF 12.3 1区 生物学
Genome Biology Pub Date : 2025-09-09 DOI: 10.1186/s13059-025-03739-8
Gijs Selten, Ronnie de Jonge
{"title":"Bacillus drives functional states in synthetic plant root bacterial communities","authors":"Gijs Selten, Ronnie de Jonge","doi":"10.1186/s13059-025-03739-8","DOIUrl":"https://doi.org/10.1186/s13059-025-03739-8","url":null,"abstract":"Plant roots release root exudates to attract microbes that form root communities, which in turn promote plant health and growth. Root community assembly arises from millions of interactions between microbes and the plant, leading to robust and stable microbial networks. To manage the complexity of natural root microbiomes for research purposes, scientists have developed reductionist approaches using synthetic microbial inocula (SynComs). Recently, an increasing number of studies employed SynComs to investigate root microbiome assembly and dynamics under various conditions or with specific plant mutants. These studies have identified bacterial traits linked to root competence, but if and how these traits shape root microbiome dynamics across conditions is not well understood. To explore whether bacterial trait selection follows recurrent patterns, we conducted a meta-analysis of nine SynCom studies involving plant roots. Surprisingly, we observed that root communities frequently assemble into two distinct functional states. Further analysis revealed that these states are characterized by differences in the abundance of Bacilli. We propose that these Bacilli-associated functional states are driven by microbial interactions such as quorum sensing and biofilm formation and that host activities, including root exudation and immune responses, influence these functional states. Whether natural root communities also organize into distinct functional states remains unclear, but the implications could be significant. Functional diversification within root communities may influence the effectiveness of plant-beneficial bioinoculants, particularly Bacilli-based inoculants. To optimize microbiome-driven plant benefits, a deeper understanding of the mechanisms underlying functional state differentiation in root microbiomes is needed.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"44 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017497","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}
引用次数: 0
Patterns of extreme outlier gene expression suggest an edge of chaos effect in transcriptomic networks 极端异常基因表达模式表明转录组网络中存在混沌效应的边缘
IF 12.3 1区 生物学
Genome Biology Pub Date : 2025-09-09 DOI: 10.1186/s13059-025-03709-0
Chen Xie, Sven Künzel, Wenyu Zhang, Cassandra A. Hathaway, Shelley S. Tworoger, Diethard Tautz
{"title":"Patterns of extreme outlier gene expression suggest an edge of chaos effect in transcriptomic networks","authors":"Chen Xie, Sven Künzel, Wenyu Zhang, Cassandra A. Hathaway, Shelley S. Tworoger, Diethard Tautz","doi":"10.1186/s13059-025-03709-0","DOIUrl":"https://doi.org/10.1186/s13059-025-03709-0","url":null,"abstract":"Most RNA-seq datasets harbor genes with extreme expression levels in some samples. Such extreme outliers are usually treated as technical errors and are removed from the data before further statistical analysis. Here we focus on the patterns of such outlier gene expression to investigate whether they provide insights into the underlying biology. Our study is based on multiple datasets, including data from outbred and inbred mice, GTEx data from humans, data from different Drosophila species, and single-nuclei sequencing data from human brain tissues. All show comparable general patterns of outlier gene expression, indicating this as a generalizable biological effect. Different individuals can harbor very different numbers of outlier genes, with some individuals showing extreme numbers in only one out of several organs. Outlier gene expression occurs as part of co-regulatory modules, some of which correspond to known pathways. In a three-generation family analysis in mice, we find that most extreme over-expression is not inherited, but appears to be sporadically generated. Genes encoding prolactin and growth hormone are also among the co-regulated genes with extreme outlier expression, both in mice and humans, for which we include also a longitudinal expression analysis for protein data. We show that outlier patterns of gene expression are a biological reality occurring universally across tissues and species. Most of the outlier expression is spontaneous and not inherited. We suggest that the outlier patterns reflect edge of chaos effects that are expected for systems of non-linear interactions and feedback loops, such as gene regulatory networks. ","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"35 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017491","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}
引用次数: 0
Whole genome sequence analysis of low-density lipoprotein cholesterol across 246 K individuals 246 K个体低密度脂蛋白胆固醇全基因组序列分析
IF 12.3 1区 生物学
Genome Biology Pub Date : 2025-09-09 DOI: 10.1186/s13059-025-03698-0
Margaret Sunitha Selvaraj, Xihao Li, Zilin Li, Eric Van Buren, Sara Haidermota, Darina Postupaka, Whitney Hornsby, Joshua C. Bis, Jennifer A. Brody, Brian E. Cade, Ren-Hua Chung, Joanne E. Curran, Scott M. Damrauer, Lisa de las Fuentes, Paul S. de Vries, Ravindranath Duggirala, Barry I. Freedman, MariaElisa Graff, Xiuqing Guo, Bertha A. Hidalgo, Lifang Hou, Ryan Irvin, Renae Judy, Rita R. Kalyani, Tanika N. Kelly, Iain R. Konigsberg, Brian G. Kral, Lydia Coulter Kwee, Daniel Levy, Changwei Li, Ani W. Manichaikul, Lisa Warsinger Martin, May E. Montasser, Alanna C. Morrison, Take Naseri, Kari E. North, Jeffrey R. O’Connell, Nicholette D. Palmer, Patricia A. Peyser, Alex P. Reiner, Svati H. Shah, Roelof A. J. Smit, Jennifer A. Smith, Kent D. Taylor, Hemant Tiwari, Michael Y. Tsai, Satupa‘itea Viali, Zhe Wang, Yuxuan Wang, Wei Zhao, Donna K. Arnett, John Blangero, Eric Boerwinkle, Donald W. Bowden, Jenna C. Carlson, Yii-Der Ida Chen, Patrick T. Ellinor, Myriam Fornage, Jiang He, ..
{"title":"Whole genome sequence analysis of low-density lipoprotein cholesterol across 246 K individuals","authors":"Margaret Sunitha Selvaraj, Xihao Li, Zilin Li, Eric Van Buren, Sara Haidermota, Darina Postupaka, Whitney Hornsby, Joshua C. Bis, Jennifer A. Brody, Brian E. Cade, Ren-Hua Chung, Joanne E. Curran, Scott M. Damrauer, Lisa de las Fuentes, Paul S. de Vries, Ravindranath Duggirala, Barry I. Freedman, MariaElisa Graff, Xiuqing Guo, Bertha A. Hidalgo, Lifang Hou, Ryan Irvin, Renae Judy, Rita R. Kalyani, Tanika N. Kelly, Iain R. Konigsberg, Brian G. Kral, Lydia Coulter Kwee, Daniel Levy, Changwei Li, Ani W. Manichaikul, Lisa Warsinger Martin, May E. Montasser, Alanna C. Morrison, Take Naseri, Kari E. North, Jeffrey R. O’Connell, Nicholette D. Palmer, Patricia A. Peyser, Alex P. Reiner, Svati H. Shah, Roelof A. J. Smit, Jennifer A. Smith, Kent D. Taylor, Hemant Tiwari, Michael Y. Tsai, Satupa‘itea Viali, Zhe Wang, Yuxuan Wang, Wei Zhao, Donna K. Arnett, John Blangero, Eric Boerwinkle, Donald W. Bowden, Jenna C. Carlson, Yii-Der Ida Chen, Patrick T. Ellinor, Myriam Fornage, Jiang He, ..","doi":"10.1186/s13059-025-03698-0","DOIUrl":"https://doi.org/10.1186/s13059-025-03698-0","url":null,"abstract":"Rare genetic variation provided by whole genome sequence datasets has been relatively less explored for its contributions to human traits. Meta-analysis of sequencing data offers advantages by integrating larger sample sizes from diverse cohorts, thereby increasing the likelihood of discovering novel insights into complex traits. Furthermore, emerging methods in genome-wide rare variant association testing further improve power and interpretability. Here, we conduct the largest meta-analysis of whole genome sequencing for low-density lipoprotein cholesterol (LDL-C), a therapeutic target for coronary artery disease, analyzing data from 246 K participants and integrating 1.23B variants from the UK Biobank and the Trans-Omics for Precision Medicine (TOPMed) program. We identify numerous rare coding and non-coding gene associations related to LDL-C, with replication across 86 K participants in All of Us. Our findings are based on single-variant analyses, rare coding and non-coding variant aggregation tests, and sliding window approaches. Through this comprehensive analysis, we identify 704 novel single-variant associations, 25 novel rare coding variant aggregates, 28 novel rare non-coding variant aggregates, and one novel sliding window aggregate. This study provides a meta-analysis framework for large-scale whole genome sequence association analyses from diverse population groups, yielding novel rare non-coding variant associations.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"53 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017492","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}
引用次数: 0
DNA G-quadruplex profiling in skeletal muscle stem cells reveals functional and mechanistic insights 骨骼肌干细胞中的DNA g -四重体分析揭示了功能和机制的见解
IF 12.3 1区 生物学
Genome Biology Pub Date : 2025-09-05 DOI: 10.1186/s13059-025-03753-w
Xiaona Chen, Feng Yang, Suyang Zhang, Xiaofan Guo, Jieyu Zhao, Yulong Qiao, Liangqiang He, Yang Li, Qin Zhou, Michael Tim-Yun Ong, Chun Kit Kwok, Hao Sun, Huating Wang
{"title":"DNA G-quadruplex profiling in skeletal muscle stem cells reveals functional and mechanistic insights","authors":"Xiaona Chen, Feng Yang, Suyang Zhang, Xiaofan Guo, Jieyu Zhao, Yulong Qiao, Liangqiang He, Yang Li, Qin Zhou, Michael Tim-Yun Ong, Chun Kit Kwok, Hao Sun, Huating Wang","doi":"10.1186/s13059-025-03753-w","DOIUrl":"https://doi.org/10.1186/s13059-025-03753-w","url":null,"abstract":"DNA G-quadruplexes (G4s) are non-canonical secondary structures formed in guanine-rich DNA sequences and play important roles in modulating biological processes through a variety of gene regulatory mechanisms. Emerging G4 profiling allows global mapping of endogenous G4 formation. Here in this study, we map the G4 landscapes in adult skeletal muscle stem cells (MuSCs), which are essential for injury-induced muscle regeneration. Throughout the myogenic lineage progression of MuSCs, we uncover dynamic endogenous G4 formation with a pronounced G4 induction when MuSCs become activated and proliferating. We further demonstrate that the G4 induction promotes MuSC activation thus the regeneration process. Mechanistically, we found that promoter-associated G4s regulate gene transcription through facilitating chromatin looping. Furthermore, we found that G4 sites are enriched for transcription factor (TF) binding events in activated MuSCs; MAX binds to G4 structures to synergistically facilitate chromatin looping and gene transcription, thus promoting MuSC activation and regeneration. The above uncovered global regulatory functions/mechanisms are further dissected on the paradigm of Ccne1 promoter, demonstrating that Ccne1 is a bona fide G4/MAX regulatory target in activated MuSCs. Altogether, our findings for the first time demonstrate the prevalent and dynamic formation of G4s in adult MuSCs and the mechanistic role of G4s in modulating gene expression and MuSC activation/proliferation.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"62 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995702","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}
引用次数: 0
Artemisinin alleviates Parkinson’s disease by targeting Adcy5-Gch1 axis to trigger a cascade generation of BH4 and dopamine in rats 青蒿素通过靶向Adcy5-Gch1轴触发大鼠BH4和多巴胺级联产生来缓解帕金森病
IF 12.3 1区 生物学
Genome Biology Pub Date : 2025-09-04 DOI: 10.1186/s13059-025-03712-5
Xin-xing Yang, Guo-qing Wang, Qian Wen, Yu-jia Zhao, Dai-di Li, Feng Zhang
{"title":"Artemisinin alleviates Parkinson’s disease by targeting Adcy5-Gch1 axis to trigger a cascade generation of BH4 and dopamine in rats","authors":"Xin-xing Yang, Guo-qing Wang, Qian Wen, Yu-jia Zhao, Dai-di Li, Feng Zhang","doi":"10.1186/s13059-025-03712-5","DOIUrl":"https://doi.org/10.1186/s13059-025-03712-5","url":null,"abstract":"Parkinson’s disease is a highly prevalent neurodegenerative disorder. Hyposecretion of dopamine (DA) is the end result in the pathology of Parkinson’s disease. Unfortunately, safe and efficient therapeutic drugs are deficient. Tyrosine hydroxylase is the rate-limiting enzyme for DA synthesis, could hydroxylate tyrosine and generate levodopa with tetrahydrobiopterin (BH4) as an indispensable coenzyme. Furthermore, BH4 was confirmed to confer neuroprotection against Parkinson’s disease. Thus, regulation of BH4 synthesis was verified to become a promising therapeutic strategy for Parkinson’s disease. We demonstrate that artemisinin effectively produced neuroprotection against Parkinson’s disease in rats. Integrated analysis of midbrain proteomics and non-targeted metabolomics suggests that artemisinin might target adenylate cyclase 5 (Adcy5) to increase GTP cyclohydrolase 1 (Gch1, BH4 synthetase) expression to further boost BH4 synthesis. To verify this hypothesis, molecular docking experiments demonstrate that ART could directly bind to Adcy5. Artemisinin increases Adcy5 and Gch1 expressions and BH4 production both in vivo and in vitro. Further rescue experiments demonstrate that artemisinin-generated DA neuroprotection and hypersecretion of DA and BH4 disappears after inhibition of Adcy5 or Gch1 in vitro. Additionally, suppression of Adcy5 aggravates Parkinson’s disease manifestation, decreases midbrain DA and BH4 production and down-regulated Gch1 expression in vivo. Artemisinin mediates neuroprotection against Parkinson’s disease via regulation of Adcy5-Gch1-BH4 axis in rats. These findings present a beneficial potential for future application of artemisinin on Parkinson’s disease treatment. ","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"21 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987591","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}
引用次数: 0
RoAM: computational reconstruction of ancient methylomes and identification of differentially methylated regions RoAM:古代甲基组的计算重建和差异甲基化区域的鉴定
IF 12.3 1区 生物学
Genome Biology Pub Date : 2025-09-04 DOI: 10.1186/s13059-025-03702-7
Yoav Mathov, Naomi Rosen, Chen Leibson, Eran Meshorer, Benjamin Yakir, Liran Carmel
{"title":"RoAM: computational reconstruction of ancient methylomes and identification of differentially methylated regions","authors":"Yoav Mathov, Naomi Rosen, Chen Leibson, Eran Meshorer, Benjamin Yakir, Liran Carmel","doi":"10.1186/s13059-025-03702-7","DOIUrl":"https://doi.org/10.1186/s13059-025-03702-7","url":null,"abstract":"We present a new and considerably improved version of RoAM (Reconstruction of Ancient Methylation), a flexible tool for reconstructing ancient methylomes and identifying differentially methylated regions (DMRs) between populations. Through a series of filtering and quality control steps, RoAM produces highly reliable DNA methylation maps, making it a valuable tool for paleoepigenomics studies. We apply RoAM to pre-and post-Neolithic transition Balkan samples, and uncover DMRs in genes related to sugar metabolism. Notably, we observe post-Neolithic hypermethylation of PTPRN2, a regulator of insulin secretion. These results are compatible with hypoinsulinism in pre-Neolithic hunter-gatherers.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"61 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987592","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}
引用次数: 0
Evolutionary diversification of ancestral genes across vertebrates and insects 脊椎动物和昆虫祖先基因的进化多样化
IF 12.3 1区 生物学
Genome Biology Pub Date : 2025-09-04 DOI: 10.1186/s13059-025-03699-z
Federica Mantica, Manuel Irimia
{"title":"Evolutionary diversification of ancestral genes across vertebrates and insects","authors":"Federica Mantica, Manuel Irimia","doi":"10.1186/s13059-025-03699-z","DOIUrl":"https://doi.org/10.1186/s13059-025-03699-z","url":null,"abstract":"Vertebrates and insects diverged approximately 700 million years ago, and yet they retain a large core of conserved genes from their last common ancestor. These ancient genes present strong evolutionary constraints, which limit their overall sequence and expression divergence. However, these constraints can greatly vary across ancestral gene families and, in at least some cases, sequence and expression changes can have functional consequences. Importantly, overall patterns of sequence and expression divergence and their potential functional outcomes have never been explored in a genome-wide manner across large animal evolutionary distances. We focus on approximately 7000 highly conserved genes shared between vertebrates and insects, and we investigate global patterns of molecular diversification driven by changes in sequence and gene expression. We identify molecular features generally linked to higher or lower diversification rates, together with gene groups with similar diversification profiles in both clades. Moreover, we discover that specific sets of genes underwent differential diversification during vertebrate and insect evolution, potentially contributing to the emergence of unique phenotypes in each clade. We generate a comprehensive dataset of measures of sequence and expression divergence across vertebrates and insects, which reveals a continuous spectrum of evolutionary constraints among highly conserved genes. These constraints are normally consistent between these two clades and are associated with specific molecular features, but in some cases we also identify instances of lineage-specific diversification likely linked to functional evolution.","PeriodicalId":12611,"journal":{"name":"Genome Biology","volume":"71 1","pages":""},"PeriodicalIF":12.3,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144987694","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}
引用次数: 0
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