Cell Systems最新文献_第10页

Benchmarking transcriptional host response signatures for infection diagnosis. 对感染诊断的转录宿主反应特征进行基准测试。

IF 9.3 1区生物学

Cell Systems Pub Date : 2022-12-21 DOI: 10.1016/j.cels.2022.11.007

Daniel G Chawla, Antonio Cappuccio, Andrea Tamminga, Stuart C Sealfon, Elena Zaslavsky, Steven H Kleinstein

{"title":"Benchmarking transcriptional host response signatures for infection diagnosis.","authors":"Daniel G Chawla, Antonio Cappuccio, Andrea Tamminga, Stuart C Sealfon, Elena Zaslavsky, Steven H Kleinstein","doi":"10.1016/j.cels.2022.11.007","DOIUrl":"https://doi.org/10.1016/j.cels.2022.11.007","url":null,"abstract":"Identification of host transcriptional response signatures has emerged as a new paradigm for infection diagnosis. For clinical applications, signatures must robustly detect the pathogen of interest without cross-reacting with unintended conditions. To evaluate the performance of infectious disease signatures, we developed a framework that includes a compendium of 17,105 transcriptional profiles capturing infectious and non-infectious conditions and a standardized methodology to assess robustness and cross-reactivity. Applied to 30 published signatures of infection, the analysis showed that signatures were generally robust in detecting viral and bacterial infections in independent data. Asymptomatic and chronic infections were also detectable, albeit with decreased performance. However, many signatures were cross-reactive with unintended infections and aging. In general, we found robustness and cross-reactivity to be conflicting objectives, and we identified signature properties associated with this trade-off. The data compendium and evaluation framework developed here provide a foundation for the development of signatures for clinical application. A record of this paper's transparent peer review process is included in the supplemental information.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"13 12","pages":"974-988.e7"},"PeriodicalIF":9.3,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9768893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9102129","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}

引用次数: 3

Allelic correlation is a marker of trade-offs between barriers to transmission of expression variability and signal responsiveness in genetic networks. 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。

IF 9.3 1区生物学

Cell Systems Pub Date : 2022-12-21 Epub Date: 2022-11-29 DOI: 10.1016/j.cels.2022.10.008

Ryan H Boe, Vinay Ayyappan, Lea Schuh, Arjun Raj

{"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":"10.1016/j.cels.2022.10.008","url":null,"abstract":"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.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"13 12","pages":"1016-1032.e6"},"PeriodicalIF":9.3,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9811561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9115889","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}

引用次数: 0

The sound of silence: Transgene silencing in mammalian cell engineering. 沉默之声:哺乳动物细胞工程中的转基因沉默。

IF 9 1区生物学

Cell Systems Pub Date : 2022-12-21 DOI: 10.1016/j.cels.2022.11.005

Alan Cabrera, Hailey I Edelstein, Fokion Glykofrydis, Kasey S Love, Sebastian Palacios, Josh Tycko, Meng Zhang, Sarah Lensch, Cara E Shields, Mark Livingston, Ron Weiss, Huimin Zhao, Karmella A Haynes, Leonardo Morsut, Yvonne Y Chen, Ahmad S Khalil, Wilson W Wong, James J Collins, Susan J Rosser, Karen Polizzi, Michael B Elowitz, Martin Fussenegger, Isaac B Hilton, Joshua N Leonard, Lacramioara Bintu, Kate E Galloway, Tara L Deans

{"title":"The sound of silence: Transgene silencing in mammalian cell engineering.","authors":"Alan Cabrera, Hailey I Edelstein, Fokion Glykofrydis, Kasey S Love, Sebastian Palacios, Josh Tycko, Meng Zhang, Sarah Lensch, Cara E Shields, Mark Livingston, Ron Weiss, Huimin Zhao, Karmella A Haynes, Leonardo Morsut, Yvonne Y Chen, Ahmad S Khalil, Wilson W Wong, James J Collins, Susan J Rosser, Karen Polizzi, Michael B Elowitz, Martin Fussenegger, Isaac B Hilton, Joshua N Leonard, Lacramioara Bintu, Kate E Galloway, Tara L Deans","doi":"10.1016/j.cels.2022.11.005","DOIUrl":"10.1016/j.cels.2022.11.005","url":null,"abstract":"To elucidate principles operating in native biological systems and to develop novel biotechnologies, synthetic biology aims to build and integrate synthetic gene circuits within native transcriptional networks. The utility of synthetic gene circuits for cell engineering relies on the ability to control the expression of all constituent transgene components. Transgene silencing, defined as the loss of expression over time, persists as an obstacle for engineering primary cells and stem cells with transgenic cargos. In this review, we highlight the challenge that transgene silencing poses to the robust engineering of mammalian cells, outline potential molecular mechanisms of silencing, and present approaches for preventing transgene silencing. We conclude with a perspective identifying future research directions for improving the performance of synthetic gene circuits.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"13 12","pages":"950-973"},"PeriodicalIF":9.0,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9880859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9760012","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}

引用次数: 0

Lactate-dependent chaperone-mediated autophagy induces oscillatory HIF-1α activity promoting proliferation of hypoxic cells. 乳酸依赖性伴侣介导的自噬诱导 HIF-1α 的振荡活性，促进缺氧细胞的增殖。

IF 9.3 1区生物学

Cell Systems Pub Date : 2022-12-21 Epub Date: 2022-12-02 DOI: 10.1016/j.cels.2022.11.003

Kshitiz, Junaid Afzal, Yasir Suhail, Hao Chang, Maimon E Hubbi, Archer Hamidzadeh, Ruchi Goyal, Yamin Liu, Peng Sun, Stefania Nicoli, Chi V Dang, Andre Levchenko

{"title":"Lactate-dependent chaperone-mediated autophagy induces oscillatory HIF-1α activity promoting proliferation of hypoxic cells.","authors":"Kshitiz, Junaid Afzal, Yasir Suhail, Hao Chang, Maimon E Hubbi, Archer Hamidzadeh, Ruchi Goyal, Yamin Liu, Peng Sun, Stefania Nicoli, Chi V Dang, Andre Levchenko","doi":"10.1016/j.cels.2022.11.003","DOIUrl":"10.1016/j.cels.2022.11.003","url":null,"abstract":"Response to hypoxia is a highly regulated process, but little is known about single-cell responses to hypoxic conditions. Using fluorescent reporters of hypoxia response factor-1α (HIF-1α) activity in various cancer cell lines and patient-derived cancer cells, we show that hypoxic responses in individual cancer cells can be highly dynamic and variable. These responses fall into three classes, including oscillatory activity. We identify a molecular mechanism that can account for all three response classes, implicating reactive-oxygen-species-dependent chaperone-mediated autophagy of HIF-1α in a subset of cells. Furthermore, we show that oscillatory response is modulated by the abundance of extracellular lactate in a quorum-sensing-like mechanism. We show that oscillatory HIF-1α activity rescues hypoxia-mediated inhibition of cell division and causes broad suppression of genes downregulated in cancers and activation of genes upregulated in many cancers, suggesting a mechanism for aggressive growth in a subset of hypoxic tumor cells.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"13 12","pages":"1048-1064.e7"},"PeriodicalIF":9.3,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10012408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9633239","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}

引用次数: 0

How can systems approaches help us understand and treat infectious disease? 系统方法如何帮助我们理解和治疗传染病?

IF 9.3 1区生物学

Cell Systems Pub Date : 2022-12-21 DOI: 10.1016/j.cels.2022.11.009

Anna Kuchina, Jason Yang, Bree Aldridge, Kevin A Janes, Naeha Subramanian, Nevan J Krogan, Mehdi Bouhaddou, Shirit Einav, Jason Papin, Ronald N Germain

引用次数: 0

Recent progress of gene circuit designs in immune cell therapies. 基因回路设计在免疫细胞治疗中的最新进展。

IF 9 1区生物学

Cell Systems Pub Date : 2022-11-16 DOI: 10.1016/j.cels.2022.09.006

Seunghee Lee, Ahmad S Khalil, Wilson W Wong

引用次数: 0

Systems analysis of de novo mutations in congenital heart diseases identified a protein network in the hypoplastic left heart syndrome. 先天性心脏病新生突变的系统分析确定了左心发育不全综合征的蛋白质网络。

IF 9.3 1区生物学

Cell Systems Pub Date : 2022-11-16 Epub Date: 2022-09-26 DOI: 10.1016/j.cels.2022.09.001

Yuejun Jessie Wang, Xicheng Zhang, Chi Keung Lam, Hongchao Guo, Cheng Wang, Sai Zhang, Joseph C Wu, Michael Snyder, Jingjing Li

{"title":"Systems analysis of de novo mutations in congenital heart diseases identified a protein network in the hypoplastic left heart syndrome.","authors":"Yuejun Jessie Wang, Xicheng Zhang, Chi Keung Lam, Hongchao Guo, Cheng Wang, Sai Zhang, Joseph C Wu, Michael Snyder, Jingjing Li","doi":"10.1016/j.cels.2022.09.001","DOIUrl":"10.1016/j.cels.2022.09.001","url":null,"abstract":"Despite a strong genetic component, only a few genes have been identified in congenital heart diseases (CHDs). We introduced systems analyses to uncover the hidden organization on biological networks of mutations in CHDs and leveraged network analysis to integrate the protein interactome, patient exomes, and single-cell transcriptomes of the developing heart. We identified a CHD network regulating heart development and observed that a sub-network also regulates fetal brain development, thereby providing mechanistic insights into the clinical comorbidities between CHDs and neurodevelopmental conditions. At a small scale, we experimentally verified uncharacterized cardiac functions of several proteins. At a global scale, our study revealed developmental dynamics of the network and observed its association with the hypoplastic left heart syndrome (HLHS), which was further supported by the dysregulation of the network in HLHS endothelial cells. Overall, our work identified previously uncharacterized CHD factors and provided a generalizable framework applicable to studying many other complex diseases. A record of this paper's Transparent Peer Review process is included in the supplemental information.","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":"13 11","pages":"895-910.e4"},"PeriodicalIF":9.3,"publicationDate":"2022-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9671831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9718927","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}

引用次数: 0

Somatic XIST activation and features of X chromosome inactivation in male human cancers. 男性癌症患者的体细胞XIST激活及X染色体失活特征。

IF 9.3 1区生物学

Cell Systems Pub Date : 2022-11-16 DOI: 10.1016/j.cels.2022.10.002

Ananthan Sadagopan, Imran T Nasim, Jiao Li, Mingkee Achom, Cheng-Zhong Zhang, Srinivas R Viswanathan

引用次数: 5

Evaluation of Peterson et al.: MAPK cascades don't work in silos: MAP3K cross-activation of MAPKs and the effect of crosstalk on cellular responses. 对Peterson等人的评价:MAPK级联并不孤立地起作用:MAP3K的交叉激活和串扰对细胞反应的影响。

IF 9.3 1区生物学

Cell Systems Pub Date : 2022-11-16 DOI: 10.1016/j.cels.2022.10.004

Jeremiah Keyes

引用次数: 0

Should I stay, or should I go? Gene retention in organellar genomes. 我该留下还是走?细胞器基因组中的基因保留。

IF 9.3 1区生物学

Cell Systems Pub Date : 2022-11-16 DOI: 10.1016/j.cels.2022.10.006

Lantana K Grub, Nikita Tsyba, Maulik R Patel

引用次数: 0