{"title":"Progress in understanding the vertebrate segmentation clock","authors":"Akihiro Isomura, Ryoichiro Kageyama","doi":"10.1038/s41576-025-00813-6","DOIUrl":"https://doi.org/10.1038/s41576-025-00813-6","url":null,"abstract":"<p>The segmentation clock is a molecular oscillator that regulates the periodic formation of somites from the presomitic mesoderm during vertebrate embryogenesis. Synchronous oscillatory expression of a Hairy homologue or Hairy-related basic helix–loop–helix (bHLH) transcriptional repressor in presomitic mesoderm cells regulates periodic expression of downstream factors that control somite segmentation with a periodicity that varies across species. Although many of the key components of the clock have been identified and characterized, less is known about how the clock is synchronized across cells and how species-specific periodicity is achieved. Advances in live imaging, stem cell and organoid technologies, and synthetic approaches have started to uncover the detailed mechanisms underlying these aspects of somitogenesis, providing insight into how morphogenesis is coordinated in space and time during embryonic development.</p>","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"23 1","pages":""},"PeriodicalIF":42.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538296","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}
David A. Selby, Maximilian Sprang, Jan Ewald, Sebastian J. Vollmer
{"title":"Beyond the black box with biologically informed neural networks","authors":"David A. Selby, Maximilian Sprang, Jan Ewald, Sebastian J. Vollmer","doi":"10.1038/s41576-025-00826-1","DOIUrl":"https://doi.org/10.1038/s41576-025-00826-1","url":null,"abstract":"Machine learning models for multi-omics data often trade off predictive accuracy against biological interpretability. An emerging class of deep learning architectures structurally encode biological knowledge to improve both prediction and explainability. Opportunities and challenges remain for broader adoption. Biologically informed neural networks promise to lead to more explainable, data-driven discoveries in genomics, drug development and precision medicine. Selby et al. highlight emerging opportunities, as well as challenges that will need to be overcome to enable their wider adoption.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"32 1","pages":""},"PeriodicalIF":42.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538429","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":"Tracking protein binding to cis-regulatory elements with PRINT","authors":"Yan Hu","doi":"10.1038/s41576-025-00823-4","DOIUrl":"https://doi.org/10.1038/s41576-025-00823-4","url":null,"abstract":"In this Tools of the Trade article, Yan Hu explains the development and application of PRINT and seq2PRINT, computational tools that together use single-cell ATAC-seq data to predict protein binding dynamics at detailed cellular resolution.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"22 1","pages":""},"PeriodicalIF":42.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462436","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":"Intrinsically disordered regions as facilitators of the transcription factor target search","authors":"Felix Jonas, Yoav Navon, Naama Barkai","doi":"10.1038/s41576-025-00816-3","DOIUrl":"https://doi.org/10.1038/s41576-025-00816-3","url":null,"abstract":"<p>Transcription factors (TFs) contribute to organismal development and function by regulating gene expression. Despite decades of research, the factors determining the specificity and speed at which eukaryotic TFs detect their target binding sites remain poorly understood. Recent studies have pointed to intrinsically disordered regions (IDRs) within TFs as key regulators of the process by which TFs find their target sites on DNA (the TF target search). However, IDRs are challenging to study because they can confer specificity despite low sequence complexity and can be functionally conserved despite rapid sequence divergence. Nevertheless, emerging computational and experimental approaches are beginning to elucidate the sequence–function relationship within the IDRs of TFs. Additional insights are informing potential mechanisms underlying the IDR-directed search for the DNA targets of TFs, including incorporation into biomolecular condensates, facilitating TF co-localization, and the hypothesis that IDRs recognize and directly interact with specific genomic regions.</p>","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"176 1","pages":""},"PeriodicalIF":42.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462486","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":"Decoding cell–cell communication using spatial transcriptomics","authors":"Ankit Agrawal","doi":"10.1038/s41576-025-00824-3","DOIUrl":"https://doi.org/10.1038/s41576-025-00824-3","url":null,"abstract":"In this Tools of the Trade article, Ankit Agrawal introduces the computational framework NiCo (Niche Covariation), which integrates spatial transcriptomics with single-cell RNA-sequencing data to study cell–cell communication.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"209 1","pages":""},"PeriodicalIF":42.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462487","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":"Genomic data sharing: you don’t know what you’ve got (till it’s gone)","authors":"Kathryn E. Holt, Michael Inouye","doi":"10.1038/s41576-025-00820-7","DOIUrl":"https://doi.org/10.1038/s41576-025-00820-7","url":null,"abstract":"Genomics research has thrived under a culture of data sharing, formalized during the genome-project era. As the field’s complexity has increased to the population scale this culture risks being eroded, yet the core principles still apply. The community would benefit from more open discussion and consensus-building around biological data sharing, recognizing that the answer will shape what the practice of science looks like in future. Reflecting on the core values of early data sharing agreements, the Bermuda Principles and the Fort Lauderdale Agreement, Kathryn E. Holt and Michael Inouye emphasize the need to reaffirm our commitment to genomic data sharing to shape the future of science.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"56 1","pages":""},"PeriodicalIF":42.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393014","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":"Spatial miRNomics: towards the integration of microRNAs in spatial biology","authors":"Agustín Robles-Remacho, Mats Nilsson","doi":"10.1038/s41576-025-00819-0","DOIUrl":"https://doi.org/10.1038/s41576-025-00819-0","url":null,"abstract":"Spatial transcriptomics tools enable the detection and localization of hundreds to thousands of transcripts in biological tissues. However, most technologies are not designed to detect microRNAs. Existing technologies should be expanded to incorporate these key molecular regulators and enable more-comprehensive transcriptomic studies that will shape the new field of spatial miRNomics. In this Comment, Agustín Robles-Remacho and Mats Nilsson highlight the opportunities and challenges of using spatial transcriptomics to detect and localize microRNAs in biological tissues, and advocate for the increased development of existing spatial transcriptomics methods.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"40 1","pages":""},"PeriodicalIF":42.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192058","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}
Raquel G. Hernandez, Simoné Guambaña, Melissa W. VonDran, Patrick M. Van Hoose, Thomas J. Bell, Melissa A. Faith
{"title":"Integrating ELSI study teams in paediatric genomic research efforts","authors":"Raquel G. Hernandez, Simoné Guambaña, Melissa W. VonDran, Patrick M. Van Hoose, Thomas J. Bell, Melissa A. Faith","doi":"10.1038/s41576-025-00818-1","DOIUrl":"https://doi.org/10.1038/s41576-025-00818-1","url":null,"abstract":"Addressing ethical, legal and social implications (ELSI) in genomics requires early integration of specialized teams to enhance community engagement, address disparities and promote health equity. Lessons learnt from the human Developmental Genotype-Tissue Expression (dGTEx) project show how implementing a collaborative framework can support genomic discovery. The promise of paediatric genomics depends on proactively addressing complex ethical and equity issues with sustained community engagement. Hernandez et al. advocate for the integration of ELSI scholars into paediatric genomic study teams to catalyse timely discovery in genomics.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"61 1","pages":""},"PeriodicalIF":42.7,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077623","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":"Spatial metabolomics to unravel cellular metabolism","authors":"Arafath K. Najumudeen, Johan Vande Voorde","doi":"10.1038/s41576-025-00817-2","DOIUrl":"https://doi.org/10.1038/s41576-025-00817-2","url":null,"abstract":"In this Tools of the Trade article, Arafath Najumudeen and Johan Vande Voorde showcase the potential of mass spectrometry imaging for spatial metabolomics by highlighting its application in cancer, revealing metabolic differences between cell populations in the tumour microenvironment.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"19 1","pages":""},"PeriodicalIF":42.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049947","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":"The early days of transcriptome sequencing and functional genomics","authors":"Ayako Suzuki","doi":"10.1038/s41576-025-00814-5","DOIUrl":"10.1038/s41576-025-00814-5","url":null,"abstract":"Ayako Suzuki recalls two papers published in the early 2000s by the Functional Annotation of the Mammalian Genome (FANTOM) consortium and the Full-Length Long Japan (FLJ) project, which provided reference catalogues of full-length transcripts in mice and humans, respectively.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"26 3","pages":"155-155"},"PeriodicalIF":39.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055053","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}
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