Pub Date : 2025-01-29DOI: 10.1038/s41588-024-02067-0
Mitchell R. Vollger, Jonas Korlach, Kiara C. Eldred, Elliott Swanson, Jason G. Underwood, Stephanie C. Bohaczuk, Yizi Mao, Yong-Han H. Cheng, Jane Ranchalis, Elizabeth E. Blue, Ulrike Schwarze, Katherine M. Munson, Christopher T. Saunders, Aaron M. Wenger, Aimee Allworth, Sirisak Chanprasert, Brittney L. Duerden, Ian Glass, Martha Horike-Pyne, Michelle Kim, Kathleen A. Leppig, Ian J. McLaughlin, Jessica Ogawa, Elisabeth A. Rosenthal, Sam Sheppeard, Stephanie M. Sherman, Samuel Strohbehn, Amy L. Yuen, Andrew W. Stacey, University of Washington Center for Rare Disease Research, Undiagnosed Diseases Network, Thomas A. Reh, Peter H. Byers, Michael J. Bamshad, Fuki M. Hisama, Gail P. Jarvik, Yasemin Sancak, Katrina M. Dipple, Andrew B. Stergachis
Resolving the molecular basis of a Mendelian condition remains challenging owing to the diverse mechanisms by which genetic variants cause disease. To address this, we developed a synchronized long-read genome, methylome, epigenome and transcriptome sequencing approach, which enables accurate single-nucleotide, insertion–deletion and structural variant calling and diploid de novo genome assembly. This permits the simultaneous elucidation of haplotype-resolved CpG methylation, chromatin accessibility and full-length transcript information in a single long-read sequencing run. Application of this approach to an Undiagnosed Diseases Network participant with a chromosome X;13-balanced translocation of uncertain significance revealed that this translocation disrupted the functioning of four separate genes (NBEA, PDK3, MAB21L1 and RB1) previously associated with single-gene Mendelian conditions. Notably, the function of each gene was disrupted via a distinct mechanism that required integration of the four ‘omes’ to resolve. These included fusion transcript formation, enhancer adoption, transcriptional readthrough silencing and inappropriate X-chromosome inactivation of autosomal genes. Overall, this highlights the utility of synchronized long-read multi-omic profiling for mechanistically resolving complex phenotypes. Simultaneous profiling of the genome, methylome, epigenome and transcriptome using single-molecule chromatin fiber sequencing and multiplexed arrays isoform sequencing identifies the genetic and molecular basis of an undiagnosed Mendelian disease case with an X;13-balanced translocation.
{"title":"Synchronized long-read genome, methylome, epigenome and transcriptome profiling resolve a Mendelian condition","authors":"Mitchell R. Vollger, Jonas Korlach, Kiara C. Eldred, Elliott Swanson, Jason G. Underwood, Stephanie C. Bohaczuk, Yizi Mao, Yong-Han H. Cheng, Jane Ranchalis, Elizabeth E. Blue, Ulrike Schwarze, Katherine M. Munson, Christopher T. Saunders, Aaron M. Wenger, Aimee Allworth, Sirisak Chanprasert, Brittney L. Duerden, Ian Glass, Martha Horike-Pyne, Michelle Kim, Kathleen A. Leppig, Ian J. McLaughlin, Jessica Ogawa, Elisabeth A. Rosenthal, Sam Sheppeard, Stephanie M. Sherman, Samuel Strohbehn, Amy L. Yuen, Andrew W. Stacey, University of Washington Center for Rare Disease Research, Undiagnosed Diseases Network, Thomas A. Reh, Peter H. Byers, Michael J. Bamshad, Fuki M. Hisama, Gail P. Jarvik, Yasemin Sancak, Katrina M. Dipple, Andrew B. Stergachis","doi":"10.1038/s41588-024-02067-0","DOIUrl":"10.1038/s41588-024-02067-0","url":null,"abstract":"Resolving the molecular basis of a Mendelian condition remains challenging owing to the diverse mechanisms by which genetic variants cause disease. To address this, we developed a synchronized long-read genome, methylome, epigenome and transcriptome sequencing approach, which enables accurate single-nucleotide, insertion–deletion and structural variant calling and diploid de novo genome assembly. This permits the simultaneous elucidation of haplotype-resolved CpG methylation, chromatin accessibility and full-length transcript information in a single long-read sequencing run. Application of this approach to an Undiagnosed Diseases Network participant with a chromosome X;13-balanced translocation of uncertain significance revealed that this translocation disrupted the functioning of four separate genes (NBEA, PDK3, MAB21L1 and RB1) previously associated with single-gene Mendelian conditions. Notably, the function of each gene was disrupted via a distinct mechanism that required integration of the four ‘omes’ to resolve. These included fusion transcript formation, enhancer adoption, transcriptional readthrough silencing and inappropriate X-chromosome inactivation of autosomal genes. Overall, this highlights the utility of synchronized long-read multi-omic profiling for mechanistically resolving complex phenotypes. Simultaneous profiling of the genome, methylome, epigenome and transcriptome using single-molecule chromatin fiber sequencing and multiplexed arrays isoform sequencing identifies the genetic and molecular basis of an undiagnosed Mendelian disease case with an X;13-balanced translocation.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 2","pages":"469-479"},"PeriodicalIF":31.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055384","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}
Pub Date : 2025-01-28DOI: 10.1038/s41588-024-02059-0
Shengqian Xia, Jianhai Chen, Deanna Arsala, J. J. Emerson, Manyuan Long
In the past decade, our understanding of how new genes originate in diverse organisms has advanced substantially, and more than a dozen molecular mechanisms for generating initial gene structures were identified, in addition to gene duplication. These new genes have been found to integrate into and modify pre-existing gene networks primarily through mutation and selection, revealing new patterns and rules with stable origination rates across various organisms. This progress has challenged the prevailing belief that new proteins evolve from pre-existing genes, as new genes may arise de novo from noncoding DNA sequences in many organisms, with high rates observed in flowering plants. New genes have important roles in phenotypic and functional evolution across diverse biological processes and structures, with detectable fitness effects of sexual conflict genes that can shape species divergence. Such knowledge of new genes can be of translational value in agriculture and medicine. This Review discusses the various molecular mechanisms underlying the generation of new genes and highlights their important functions and phenotypes with an emphasis on the evolutionary forces underlying natural selection and sexual conflict.
{"title":"Functional innovation through new genes as a general evolutionary process","authors":"Shengqian Xia, Jianhai Chen, Deanna Arsala, J. J. Emerson, Manyuan Long","doi":"10.1038/s41588-024-02059-0","DOIUrl":"10.1038/s41588-024-02059-0","url":null,"abstract":"In the past decade, our understanding of how new genes originate in diverse organisms has advanced substantially, and more than a dozen molecular mechanisms for generating initial gene structures were identified, in addition to gene duplication. These new genes have been found to integrate into and modify pre-existing gene networks primarily through mutation and selection, revealing new patterns and rules with stable origination rates across various organisms. This progress has challenged the prevailing belief that new proteins evolve from pre-existing genes, as new genes may arise de novo from noncoding DNA sequences in many organisms, with high rates observed in flowering plants. New genes have important roles in phenotypic and functional evolution across diverse biological processes and structures, with detectable fitness effects of sexual conflict genes that can shape species divergence. Such knowledge of new genes can be of translational value in agriculture and medicine. This Review discusses the various molecular mechanisms underlying the generation of new genes and highlights their important functions and phenotypes with an emphasis on the evolutionary forces underlying natural selection and sexual conflict.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 2","pages":"295-309"},"PeriodicalIF":31.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049996","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}
Pub Date : 2025-01-24DOI: 10.1038/s41588-024-02048-3
Or Lazarescu, Maya Ziv-Agam, Yulia Haim, Idan Hekselman, Juman Jubran, Ariel Shneyour, Habib Muallem, Alon Zemer, Marina Rosengarten-Levin, Daniel Kitsberg, Liron Levin, Idit F. Liberty, Uri Yoel, Oleg Dukhno, Miriam Adam, Julia Braune, Claudia Müller, Nora Raulien, Martin Gericke, Antje Körner, Rinki Murphy, Matthias Blüher, Naomi Habib, Assaf Rudich, Esti Yeger-Lotem
Human adipose depots are functionally distinct. Yet, recent single-nucleus RNA sequencing (snRNA-seq) analyses largely uncovered overlapping or similar cell-type landscapes. We hypothesized that adipocyte subtypes, differentiation trajectories and/or intercellular communication patterns could illuminate this depot similarity–difference gap. For this, we performed snRNA-seq of human subcutaneous or visceral adipose tissues (five or ten samples, respectively). Of 27,665 adipocyte nuclei in both depots, most were ‘classical’, namely enriched in lipid metabolism pathways. However, we also observed ‘nonclassical’ adipocyte subtypes, enriched in immune-related, extracellular matrix deposition (fibrosis), vascularization or angiogenesis or ribosomal and mitochondrial processes. Pseudo-temporal analysis showed a developmental trajectory from adipose progenitor cells to classical adipocytes via nonclassical adipocytes, suggesting that the classical state stems from loss, rather than gain, of specialized functions. Last, intercellular communication routes were consistent with the different inflammatory tone of the two depots. Jointly, these findings provide a high-resolution view into the contribution of cellular composition, differentiation and intercellular communication patterns to human fat depot differences. Single-nucleus RNA sequencing of human visceral and subcutaneous adipose tissues is used to identify adipocyte subpopulations and explore their developmental trajectories and interactions.
{"title":"Human subcutaneous and visceral adipocyte atlases uncover classical and nonclassical adipocytes and depot-specific patterns","authors":"Or Lazarescu, Maya Ziv-Agam, Yulia Haim, Idan Hekselman, Juman Jubran, Ariel Shneyour, Habib Muallem, Alon Zemer, Marina Rosengarten-Levin, Daniel Kitsberg, Liron Levin, Idit F. Liberty, Uri Yoel, Oleg Dukhno, Miriam Adam, Julia Braune, Claudia Müller, Nora Raulien, Martin Gericke, Antje Körner, Rinki Murphy, Matthias Blüher, Naomi Habib, Assaf Rudich, Esti Yeger-Lotem","doi":"10.1038/s41588-024-02048-3","DOIUrl":"10.1038/s41588-024-02048-3","url":null,"abstract":"Human adipose depots are functionally distinct. Yet, recent single-nucleus RNA sequencing (snRNA-seq) analyses largely uncovered overlapping or similar cell-type landscapes. We hypothesized that adipocyte subtypes, differentiation trajectories and/or intercellular communication patterns could illuminate this depot similarity–difference gap. For this, we performed snRNA-seq of human subcutaneous or visceral adipose tissues (five or ten samples, respectively). Of 27,665 adipocyte nuclei in both depots, most were ‘classical’, namely enriched in lipid metabolism pathways. However, we also observed ‘nonclassical’ adipocyte subtypes, enriched in immune-related, extracellular matrix deposition (fibrosis), vascularization or angiogenesis or ribosomal and mitochondrial processes. Pseudo-temporal analysis showed a developmental trajectory from adipose progenitor cells to classical adipocytes via nonclassical adipocytes, suggesting that the classical state stems from loss, rather than gain, of specialized functions. Last, intercellular communication routes were consistent with the different inflammatory tone of the two depots. Jointly, these findings provide a high-resolution view into the contribution of cellular composition, differentiation and intercellular communication patterns to human fat depot differences. Single-nucleus RNA sequencing of human visceral and subcutaneous adipose tissues is used to identify adipocyte subpopulations and explore their developmental trajectories and interactions.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 2","pages":"413-426"},"PeriodicalIF":31.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-024-02048-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-24DOI: 10.1038/s41588-024-02052-7
Satoshi Yoshiji, Tianyuan Lu, Guillaume Butler-Laporte, Julia Carrasco-Zanini-Sanchez, Chen-Yang Su, Yiheng Chen, Kevin Liang, Julian Daniel Sunday Willett, Shidong Wang, Darin Adra, Yann Ilboudo, Takayoshi Sasako, Satoshi Koyama, Tetsushi Nakao, Vincenzo Forgetta, Yossi Farjoun, Hugo Zeberg, Sirui Zhou, Michael Marks-Hultström, Mitchell J. Machiela, Rama Kaalia, Hesam Dashti, Melina Claussnitzer, Jason Flannick, Nicholas J. Wareham, Vincent Mooser, Nicholas J. Timpson, Claudia Langenberg, J. Brent Richards
Obesity strongly increases the risk of cardiometabolic diseases, yet the underlying mediators of this relationship are not fully understood. Given that obesity strongly influences circulating protein levels, we investigated proteins mediating the effects of obesity on coronary artery disease, stroke and type 2 diabetes. By integrating two-step proteome-wide Mendelian randomization, colocalization, epigenomics and single-cell RNA sequencing, we identified five mediators and prioritized collagen type VI α3 (COL6A3). COL6A3 levels were strongly increased by body mass index and increased coronary artery disease risk. Notably, the carboxyl terminus product of COL6A3, endotrophin, drove this effect. COL6A3 was highly expressed in disease-relevant cell types and tissues. Finally, we found that body fat reduction could reduce plasma levels of COL6A3-derived endotrophin, indicating a tractable way to modify endotrophin levels. In summary, we provide actionable insights into how circulating proteins mediate the effects of obesity on cardiometabolic diseases and prioritize endotrophin as a potential therapeutic target. Two-step Mendelian randomization, combined with multiple layers of omics evidence, implicates COL6A3-derived endotrophin as a mediator of coronary artery disease risk in the context of obesity.
{"title":"Integrative proteogenomic analysis identifies COL6A3-derived endotrophin as a mediator of the effect of obesity on coronary artery disease","authors":"Satoshi Yoshiji, Tianyuan Lu, Guillaume Butler-Laporte, Julia Carrasco-Zanini-Sanchez, Chen-Yang Su, Yiheng Chen, Kevin Liang, Julian Daniel Sunday Willett, Shidong Wang, Darin Adra, Yann Ilboudo, Takayoshi Sasako, Satoshi Koyama, Tetsushi Nakao, Vincenzo Forgetta, Yossi Farjoun, Hugo Zeberg, Sirui Zhou, Michael Marks-Hultström, Mitchell J. Machiela, Rama Kaalia, Hesam Dashti, Melina Claussnitzer, Jason Flannick, Nicholas J. Wareham, Vincent Mooser, Nicholas J. Timpson, Claudia Langenberg, J. Brent Richards","doi":"10.1038/s41588-024-02052-7","DOIUrl":"10.1038/s41588-024-02052-7","url":null,"abstract":"Obesity strongly increases the risk of cardiometabolic diseases, yet the underlying mediators of this relationship are not fully understood. Given that obesity strongly influences circulating protein levels, we investigated proteins mediating the effects of obesity on coronary artery disease, stroke and type 2 diabetes. By integrating two-step proteome-wide Mendelian randomization, colocalization, epigenomics and single-cell RNA sequencing, we identified five mediators and prioritized collagen type VI α3 (COL6A3). COL6A3 levels were strongly increased by body mass index and increased coronary artery disease risk. Notably, the carboxyl terminus product of COL6A3, endotrophin, drove this effect. COL6A3 was highly expressed in disease-relevant cell types and tissues. Finally, we found that body fat reduction could reduce plasma levels of COL6A3-derived endotrophin, indicating a tractable way to modify endotrophin levels. In summary, we provide actionable insights into how circulating proteins mediate the effects of obesity on cardiometabolic diseases and prioritize endotrophin as a potential therapeutic target. Two-step Mendelian randomization, combined with multiple layers of omics evidence, implicates COL6A3-derived endotrophin as a mediator of coronary artery disease risk in the context of obesity.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 2","pages":"345-357"},"PeriodicalIF":31.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-024-02052-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-22DOI: 10.1038/s41588-024-02049-2
Jonathan E. LoTempio Jr, Jonathan D. Moreno
Since the Human Genome Project, the consensus position in genomics has been that data should be shared widely to achieve the greatest societal benefit. This position relies on imprecise definitions of the concept of ‘broad data sharing’. Accordingly, the implementation of data sharing varies among landmark genomic studies. In this Perspective, we identify definitions of broad that have been used interchangeably, despite their distinct implications. We further offer a framework with clarified concepts for genomic data sharing and probe six examples in genomics that produced public data. Finally, we articulate three challenges. First, we explore the need to reinterpret the limits of general research use data. Second, we consider the governance of public data deposition from extant samples. Third, we ask whether, in light of changing concepts of broad, participants should be encouraged to share their status as participants publicly or not. Each of these challenges is followed with recommendations. This Perspective discusses the definitions of ‘broad’ that have been used in the context of sharing of human genomic data and proposes a clarified and reformed terminology for describing genomic data sharing more precisely.
{"title":"Overcoming challenges associated with broad sharing of human genomic data","authors":"Jonathan E. LoTempio Jr, Jonathan D. Moreno","doi":"10.1038/s41588-024-02049-2","DOIUrl":"10.1038/s41588-024-02049-2","url":null,"abstract":"Since the Human Genome Project, the consensus position in genomics has been that data should be shared widely to achieve the greatest societal benefit. This position relies on imprecise definitions of the concept of ‘broad data sharing’. Accordingly, the implementation of data sharing varies among landmark genomic studies. In this Perspective, we identify definitions of broad that have been used interchangeably, despite their distinct implications. We further offer a framework with clarified concepts for genomic data sharing and probe six examples in genomics that produced public data. Finally, we articulate three challenges. First, we explore the need to reinterpret the limits of general research use data. Second, we consider the governance of public data deposition from extant samples. Third, we ask whether, in light of changing concepts of broad, participants should be encouraged to share their status as participants publicly or not. Each of these challenges is followed with recommendations. This Perspective discusses the definitions of ‘broad’ that have been used in the context of sharing of human genomic data and proposes a clarified and reformed terminology for describing genomic data sharing more precisely.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 2","pages":"287-294"},"PeriodicalIF":31.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991976","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}
Pub Date : 2025-01-22DOI: 10.1038/s41588-024-02054-5
Ricardo Mouro Pinto, Ryan Murtha, António Azevedo, Cameron Douglas, Marina Kovalenko, Jessica Ulloa, Steven Crescenti, Zoe Burch, Esaria Oliver, Maheswaran Kesavan, Shota Shibata, Antonia Vitalo, Eduarda Mota-Silva, Marion J. Riggs, Kevin Correia, Emanuela Elezi, Brigitte Demelo, Jeffrey B. Carroll, Tammy Gillis, James F. Gusella, Marcy E. MacDonald, Vanessa C. Wheeler
Huntington’s disease, one of more than 50 inherited repeat expansion disorders1, is a dominantly inherited neurodegenerative disease caused by a CAG expansion in HTT2. Inherited CAG repeat length is the primary determinant of age of onset, with human genetic studies underscoring that the disease is driven by the CAG length-dependent propensity of the repeat to further expand in the brain3–9. Routes to slowing somatic CAG expansion, therefore, hold promise for disease-modifying therapies. Several DNA repair genes, notably in the mismatch repair pathway, modify somatic expansion in Huntington’s disease mouse models10. To identify novel modifiers of somatic expansion, we used CRISPR–Cas9 editing in Huntington’s disease knock-in mice to enable in vivo screening of expansion-modifier candidates at scale. This included testing of Huntington’s disease onset modifier genes emerging from human genome-wide association studies as well as interactions between modifier genes, providing insight into pathways underlying CAG expansion and potential therapeutic targets. A novel in vivo screening strategy identifies new modifiers of somatic CAG repeat expansion that contribute to age of onset in Huntington’s disease.
{"title":"In vivo CRISPR–Cas9 genome editing in mice identifies genetic modifiers of somatic CAG repeat instability in Huntington’s disease","authors":"Ricardo Mouro Pinto, Ryan Murtha, António Azevedo, Cameron Douglas, Marina Kovalenko, Jessica Ulloa, Steven Crescenti, Zoe Burch, Esaria Oliver, Maheswaran Kesavan, Shota Shibata, Antonia Vitalo, Eduarda Mota-Silva, Marion J. Riggs, Kevin Correia, Emanuela Elezi, Brigitte Demelo, Jeffrey B. Carroll, Tammy Gillis, James F. Gusella, Marcy E. MacDonald, Vanessa C. Wheeler","doi":"10.1038/s41588-024-02054-5","DOIUrl":"10.1038/s41588-024-02054-5","url":null,"abstract":"Huntington’s disease, one of more than 50 inherited repeat expansion disorders1, is a dominantly inherited neurodegenerative disease caused by a CAG expansion in HTT2. Inherited CAG repeat length is the primary determinant of age of onset, with human genetic studies underscoring that the disease is driven by the CAG length-dependent propensity of the repeat to further expand in the brain3–9. Routes to slowing somatic CAG expansion, therefore, hold promise for disease-modifying therapies. Several DNA repair genes, notably in the mismatch repair pathway, modify somatic expansion in Huntington’s disease mouse models10. To identify novel modifiers of somatic expansion, we used CRISPR–Cas9 editing in Huntington’s disease knock-in mice to enable in vivo screening of expansion-modifier candidates at scale. This included testing of Huntington’s disease onset modifier genes emerging from human genome-wide association studies as well as interactions between modifier genes, providing insight into pathways underlying CAG expansion and potential therapeutic targets. A novel in vivo screening strategy identifies new modifiers of somatic CAG repeat expansion that contribute to age of onset in Huntington’s disease.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 2","pages":"314-322"},"PeriodicalIF":31.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-024-02054-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-22DOI: 10.1038/s41588-024-02055-4
Suphinya Sathitloetsakun, Myriam Heiman
A novel in vivo CRISPR screening platform identifies genetic modifiers of huntingtin CAG repeat somatic instability. These modifiers include known and novel genes that are promising therapeutic targets for Huntington’s disease.
{"title":"Defining genes and pathways that modify huntingtin CAG repeat somatic instability in vivo","authors":"Suphinya Sathitloetsakun, Myriam Heiman","doi":"10.1038/s41588-024-02055-4","DOIUrl":"10.1038/s41588-024-02055-4","url":null,"abstract":"A novel in vivo CRISPR screening platform identifies genetic modifiers of huntingtin CAG repeat somatic instability. These modifiers include known and novel genes that are promising therapeutic targets for Huntington’s disease.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 2","pages":"281-282"},"PeriodicalIF":31.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991913","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}
Pub Date : 2025-01-20DOI: 10.1038/s41588-025-02090-9
Samson H. Fong, Brent M. Kuenzi, Nicole M. Mattson, John Lee, Kyle Sanchez, Ana Bojorquez-Gomez, Kyle Ford, Brenton P. Munson, Katherine Licon, Sarah Bergendahl, John Paul Shen, Jason F. Kreisberg, Prashant Mali, Jeffrey H. Hager, Michael A. White, Trey Ideker
{"title":"Author Correction: A multilineage screen identifies actionable synthetic lethal interactions in human cancers","authors":"Samson H. Fong, Brent M. Kuenzi, Nicole M. Mattson, John Lee, Kyle Sanchez, Ana Bojorquez-Gomez, Kyle Ford, Brenton P. Munson, Katherine Licon, Sarah Bergendahl, John Paul Shen, Jason F. Kreisberg, Prashant Mali, Jeffrey H. Hager, Michael A. White, Trey Ideker","doi":"10.1038/s41588-025-02090-9","DOIUrl":"10.1038/s41588-025-02090-9","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 2","pages":"480-480"},"PeriodicalIF":31.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-025-02090-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-15DOI: 10.1038/s41588-024-02062-5
Michael Fletcher
{"title":"Nucleotide-resolution DNA foundation models of prokaryotic genomes","authors":"Michael Fletcher","doi":"10.1038/s41588-024-02062-5","DOIUrl":"10.1038/s41588-024-02062-5","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 1","pages":"2-2"},"PeriodicalIF":31.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986744","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：