{"title":"等位基因相关性是基因网络中表达变异性传播障碍与信号响应之间权衡的标志。","authors":"Ryan H Boe, Vinay Ayyappan, Lea Schuh, Arjun Raj","doi":"10.1016/j.cels.2022.10.008","DOIUrl":null,"url":null,"abstract":"<p><p>Genetic networks should respond to signals but prevent the transmission of spontaneous fluctuations. Limited data from mammalian cells suggest that noise transmission is uncommon, but systematic claims about noise transmission have been limited by the inability to directly measure it. Here, we build a mathematical framework modeling allelic correlation and noise transmission, showing that allelic correlation and noise transmission correspond across model parameters and network architectures. Limiting noise transmission comes with the trade-off of being unresponsive to signals, and within responsive regimes, there is a further trade-off between response time and basal noise transmission. Analysis of allele-specific single-cell RNA-sequencing data revealed that genes encoding upstream factors in signaling pathways and cell-type-specific factors have higher allelic correlation than downstream factors, suggesting they are more subject to regulation. Overall, our findings suggest that some noise transmission must result from signal responsiveness, but it can be minimized by trading off for a slower response. A record of this paper's transparent peer review process is included in the supplemental information.</p>","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"13 12","pages":"1016-1032.e6"},"PeriodicalIF":9.0000,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9811561/pdf/","citationCount":"0","resultStr":"{\"title\":\"Allelic correlation is a marker of trade-offs between barriers to transmission of expression variability and signal responsiveness in genetic networks.\",\"authors\":\"Ryan H Boe, Vinay Ayyappan, Lea Schuh, Arjun Raj\",\"doi\":\"10.1016/j.cels.2022.10.008\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Genetic networks should respond to signals but prevent the transmission of spontaneous fluctuations. Limited data from mammalian cells suggest that noise transmission is uncommon, but systematic claims about noise transmission have been limited by the inability to directly measure it. Here, we build a mathematical framework modeling allelic correlation and noise transmission, showing that allelic correlation and noise transmission correspond across model parameters and network architectures. Limiting noise transmission comes with the trade-off of being unresponsive to signals, and within responsive regimes, there is a further trade-off between response time and basal noise transmission. Analysis of allele-specific single-cell RNA-sequencing data revealed that genes encoding upstream factors in signaling pathways and cell-type-specific factors have higher allelic correlation than downstream factors, suggesting they are more subject to regulation. Overall, our findings suggest that some noise transmission must result from signal responsiveness, but it can be minimized by trading off for a slower response. A record of this paper's transparent peer review process is included in the supplemental information.</p>\",\"PeriodicalId\":54348,\"journal\":{\"name\":\"Cell Systems\",\"volume\":\"13 12\",\"pages\":\"1016-1032.e6\"},\"PeriodicalIF\":9.0000,\"publicationDate\":\"2022-12-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9811561/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell Systems\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/j.cels.2022.10.008\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/11/29 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Systems","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.cels.2022.10.008","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/11/29 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Allelic correlation is a marker of trade-offs between barriers to transmission of expression variability and signal responsiveness in genetic networks.
Genetic networks should respond to signals but prevent the transmission of spontaneous fluctuations. Limited data from mammalian cells suggest that noise transmission is uncommon, but systematic claims about noise transmission have been limited by the inability to directly measure it. Here, we build a mathematical framework modeling allelic correlation and noise transmission, showing that allelic correlation and noise transmission correspond across model parameters and network architectures. Limiting noise transmission comes with the trade-off of being unresponsive to signals, and within responsive regimes, there is a further trade-off between response time and basal noise transmission. Analysis of allele-specific single-cell RNA-sequencing data revealed that genes encoding upstream factors in signaling pathways and cell-type-specific factors have higher allelic correlation than downstream factors, suggesting they are more subject to regulation. Overall, our findings suggest that some noise transmission must result from signal responsiveness, but it can be minimized by trading off for a slower response. A record of this paper's transparent peer review process is included in the supplemental information.
Cell SystemsMedicine-Pathology and Forensic Medicine
CiteScore
16.50
自引率
1.10%
发文量
84
审稿时长
42 days
期刊介绍:
In 2015, Cell Systems was founded as a platform within Cell Press to showcase innovative research in systems biology. Our primary goal is to investigate complex biological phenomena that cannot be simply explained by basic mathematical principles. While the physical sciences have long successfully tackled such challenges, we have discovered that our most impactful publications often employ quantitative, inference-based methodologies borrowed from the fields of physics, engineering, mathematics, and computer science. We are committed to providing a home for elegant research that addresses fundamental questions in systems biology.