Cell genomics最新文献_第7页

Trans-eQTL mapping in gene sets identifies network effects of genetic variants. 基因组中的 Trans-eQTL 图谱可识别遗传变异的网络效应。

Cell genomics Pub Date : 2024-04-10 Epub Date: 2024-04-01 DOI: 10.1016/j.xgen.2024.100538

Lili Wang, Nikita Babushkin, Zhonghua Liu, Xuanyao Liu

引用次数: 0

Revealing the grammar of small RNA secretion using interpretable machine learning. 利用可解释的机器学习揭示小 RNA 分泌的语法。

Cell genomics Pub Date : 2024-04-10 Epub Date: 2024-03-08 DOI: 10.1016/j.xgen.2024.100522

Bahar Zirak, Mohsen Naghipourfar, Ali Saberi, Delaram Pouyabahar, Amirhossein Zarezadeh, Lixi Luo, Lisa Fish, Doowon Huh, Albertas Navickas, Ali Sharifi-Zarchi, Hani Goodarzi

{"title":"Revealing the grammar of small RNA secretion using interpretable machine learning.","authors":"Bahar Zirak, Mohsen Naghipourfar, Ali Saberi, Delaram Pouyabahar, Amirhossein Zarezadeh, Lixi Luo, Lisa Fish, Doowon Huh, Albertas Navickas, Ali Sharifi-Zarchi, Hani Goodarzi","doi":"10.1016/j.xgen.2024.100522","DOIUrl":"10.1016/j.xgen.2024.100522","url":null,"abstract":"Small non-coding RNAs can be secreted through a variety of mechanisms, including exosomal sorting, in small extracellular vesicles, and within lipoprotein complexes. However, the mechanisms that govern their sorting and secretion are not well understood. Here, we present ExoGRU, a machine learning model that predicts small RNA secretion probabilities from primary RNA sequences. We experimentally validated the performance of this model through ExoGRU-guided mutagenesis and synthetic RNA sequence analysis. Additionally, we used ExoGRU to reveal cis and trans factors that underlie small RNA secretion, including known and novel RNA-binding proteins (RBPs), e.g., YBX1, HNRNPA2B1, and RBM24. We also developed a novel technique called exoCLIP, which reveals the RNA interactome of RBPs within the cell-free space. Together, our results demonstrate the power of machine learning in revealing novel biological mechanisms. In addition to providing deeper insight into small RNA secretion, this knowledge can be leveraged in therapeutic and synthetic biology applications.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11019361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human gene regulatory evolution is driven by the divergence of regulatory element function in both cis and trans. 人类基因调控进化的动力来自顺式和反式调控元件功能的分化。

Cell genomics Pub Date : 2024-04-10 DOI: 10.1016/j.xgen.2024.100536

Tyler J Hansen, Sarah L Fong, Jessica K Day, John A Capra, Emily Hodges

{"title":"Human gene regulatory evolution is driven by the divergence of regulatory element function in both cis and trans.","authors":"Tyler J Hansen, Sarah L Fong, Jessica K Day, John A Capra, Emily Hodges","doi":"10.1016/j.xgen.2024.100536","DOIUrl":"https://doi.org/10.1016/j.xgen.2024.100536","url":null,"abstract":"Gene regulatory divergence between species can result from cis-acting local changes to regulatory element DNA sequences or global trans-acting changes to the regulatory environment. Understanding how these mechanisms drive regulatory evolution has been limited by challenges in identifying trans-acting changes. We present a comprehensive approach to directly identify cis- and trans-divergent regulatory elements between human and rhesus macaque lymphoblastoid cells using assay for transposase-accessible chromatin coupled to self-transcribing active regulatory region (ATAC-STARR) sequencing. In addition to thousands of cis changes, we discover an unexpected number (∼10,000) of trans changes and show that cis and trans elements exhibit distinct patterns of sequence divergence and function. We further identify differentially expressed transcription factors that underlie ∼37% of trans differences and trace how cis changes can produce cascades of trans changes. Overall, we find that most divergent elements (67%) experienced changes in both cis and trans, revealing a substantial role for trans divergence-alone and together with cis changes-in regulatory differences between species.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11019363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140861062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fragmid: A toolkit for rapid assembly and assessment of CRISPR technologies. Fragmid：用于快速组装和评估 CRISPR 技术的工具包。

Cell genomics Pub Date : 2024-03-13 DOI: 10.1016/j.xgen.2024.100525

Shondra M Pruett-Miller

引用次数: 0

The synthetic future of algal genomes. 藻类基因组合成的未来。

Cell genomics Pub Date : 2024-03-13 Epub Date: 2024-02-22 DOI: 10.1016/j.xgen.2024.100505

Hugh D Goold, Jeffrey L Moseley, Kyle J Lauersen

引用次数: 0

In vivo CRISPR screening directly targeting testicular cells. 直接针对睾丸细胞的体内 CRISPR 筛选。

Cell genomics Pub Date : 2024-03-13 Epub Date: 2024-03-05 DOI: 10.1016/j.xgen.2024.100510

Yuki Noguchi, Yasuhito Onodera, Tatsuo Miyamoto, Masahiro Maruoka, Hidetaka Kosako, Jun Suzuki

{"title":"In vivo CRISPR screening directly targeting testicular cells.","authors":"Yuki Noguchi, Yasuhito Onodera, Tatsuo Miyamoto, Masahiro Maruoka, Hidetaka Kosako, Jun Suzuki","doi":"10.1016/j.xgen.2024.100510","DOIUrl":"10.1016/j.xgen.2024.100510","url":null,"abstract":"CRISPR-Cas9 short guide RNA (sgRNA) library screening is a powerful approach to understand the molecular mechanisms of biological phenomena. However, its in vivo application is currently limited. Here, we developed our previously established in vitro revival screening method into an in vivo one to identify factors involved in spermatogenesis integrity by utilizing sperm capacitation as an indicator. By introducing an sgRNA library into testicular cells, we successfully pinpointed the retinal degeneration 3 (Rd3) gene as a significant factor in spermatogenesis. Single-cell RNA sequencing (scRNA-seq) analysis highlighted the high expression of Rd3 in round spermatids, and proteomics analysis indicated that Rd3 interacts with mitochondria. To search for cell-type-specific signaling pathways based on scRNA-seq and proteomics analyses, we developed a computational tool, Hub-Explorer. Through this, we discovered that Rd3 modulates oxidative stress by regulating mitochondrial distribution upon ciliogenesis induction. Collectively, our screening system provides a valuable in vivo approach to decipher molecular mechanisms in biological processes.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10943590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140051234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic associations with ratios between protein levels detect new pQTLs and reveal protein-protein interactions. 与蛋白质水平之间比率的遗传关联可发现新的 pQTLs 并揭示蛋白质与蛋白质之间的相互作用。

Cell genomics Pub Date : 2024-03-13 Epub Date: 2024-02-26 DOI: 10.1016/j.xgen.2024.100506

Karsten Suhre

引用次数: 0

Diet composition impacts eQTL discovery across multiple tissues in baboons. 饮食组成影响狒狒多种组织的 eQTL 发现。

Cell genomics Pub Date : 2024-03-13 DOI: 10.1016/j.xgen.2024.100524

Rachel M Petersen, Amanda J Lea

引用次数: 0

Modular vector assembly enables rapid assessment of emerging CRISPR technologies. 模块化载体组装可快速评估新兴的 CRISPR 技术。

Cell genomics Pub Date : 2024-03-13 DOI: 10.1016/j.xgen.2024.100519

Abby V McGee, Yanjing V Liu, Audrey L Griffith, Zsofia M Szegletes, Bronte Wen, Carolyn Kraus, Nathan W Miller, Ryan J Steger, Berta Escude Velasco, Justin A Bosch, Jonathan D Zirin, Raghuvir Viswanatha, Erik J Sontheimer, Amy Goodale, Matthew A Greene, Thomas M Green, John G Doench

{"title":"Modular vector assembly enables rapid assessment of emerging CRISPR technologies.","authors":"Abby V McGee, Yanjing V Liu, Audrey L Griffith, Zsofia M Szegletes, Bronte Wen, Carolyn Kraus, Nathan W Miller, Ryan J Steger, Berta Escude Velasco, Justin A Bosch, Jonathan D Zirin, Raghuvir Viswanatha, Erik J Sontheimer, Amy Goodale, Matthew A Greene, Thomas M Green, John G Doench","doi":"10.1016/j.xgen.2024.100519","DOIUrl":"10.1016/j.xgen.2024.100519","url":null,"abstract":"The diversity of CRISPR systems, coupled with scientific ingenuity, has led to an explosion of applications; however, to test newly described innovations in their model systems, researchers typically embark on cumbersome, one-off cloning projects to generate custom reagents that are optimized for their biological questions. Here, we leverage Golden Gate cloning to create the Fragmid toolkit, a modular set of CRISPR cassettes and delivery technologies, along with a web portal, resulting in a combinatorial platform that enables scalable vector assembly within days. We further demonstrate that multiple CRISPR technologies can be assessed in parallel in a pooled screening format using this resource, enabling the rapid optimization of both novel technologies and cellular models. These results establish Fragmid as a robust system for the rapid design of CRISPR vectors, and we anticipate that this assembly approach will be broadly useful for systematic development, comparison, and dissemination of CRISPR technologies.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10943585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic regulatory effects in response to a high-cholesterol, high-fat diet in baboons. 狒狒对高胆固醇、高脂肪饮食的遗传调控效应。

Cell genomics Pub Date : 2024-03-13 Epub Date: 2024-03-01 DOI: 10.1016/j.xgen.2024.100509

Wenhe Lin, Jeffrey D Wall, Ge Li, Deborah Newman, Yunqi Yang, Mark Abney, John L VandeBerg, Michael Olivier, Yoav Gilad, Laura A Cox

{"title":"Genetic regulatory effects in response to a high-cholesterol, high-fat diet in baboons.","authors":"Wenhe Lin, Jeffrey D Wall, Ge Li, Deborah Newman, Yunqi Yang, Mark Abney, John L VandeBerg, Michael Olivier, Yoav Gilad, Laura A Cox","doi":"10.1016/j.xgen.2024.100509","DOIUrl":"10.1016/j.xgen.2024.100509","url":null,"abstract":"Steady-state expression quantitative trait loci (eQTLs) explain only a fraction of disease-associated loci identified through genome-wide association studies (GWASs), while eQTLs involved in gene-by-environment (GxE) interactions have rarely been characterized in humans due to experimental challenges. Using a baboon model, we found hundreds of eQTLs that emerge in adipose, liver, and muscle after prolonged exposure to high dietary fat and cholesterol. Diet-responsive eQTLs exhibit genomic localization and genic features that are distinct from steady-state eQTLs. Furthermore, the human orthologs associated with diet-responsive eQTLs are enriched for GWAS genes associated with human metabolic traits, suggesting that context-responsive eQTLs with more complex regulatory effects are likely to explain GWAS hits that do not seem to overlap with standard eQTLs. Our results highlight the complexity of genetic regulatory effects and the potential of eQTLs with disease-relevant GxE interactions in enhancing the understanding of GWAS signals for human complex disease using non-human primate models.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10943580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140023539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0