NPJ Systems Biology and Applications最新文献_第2页

Impacts of the feedback loop between sense-antisense RNAs in regulating circadian rhythms. 有义-反义 RNA 之间的反馈回路对调节昼夜节律的影响

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2024-10-16 DOI: 10.1038/s41540-024-00451-4

Koichiro Uriu, Juan P Hernandez-Sanchez, Shihoko Kojima

引用次数: 0

Systems profiling reveals recurrently dysregulated cytokine signaling responses in ER+ breast cancer patients' blood. 系统剖析揭示了ER+乳腺癌患者血液中反复失调的细胞因子信号反应。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2024-10-10 DOI: 10.1038/s41540-024-00447-0

Brian Orcutt-Jahns, Joao Rodrigues Lima Junior, Emily Lin, Russell C Rockne, Adina Matache, Sergio Branciamore, Ethan Hung, Andrei S Rodin, Peter P Lee, Aaron S Meyer

{"title":"Systems profiling reveals recurrently dysregulated cytokine signaling responses in ER+ breast cancer patients' blood.","authors":"Brian Orcutt-Jahns, Joao Rodrigues Lima Junior, Emily Lin, Russell C Rockne, Adina Matache, Sergio Branciamore, Ethan Hung, Andrei S Rodin, Peter P Lee, Aaron S Meyer","doi":"10.1038/s41540-024-00447-0","DOIUrl":"10.1038/s41540-024-00447-0","url":null,"abstract":"Cytokines operate in concert to maintain immune homeostasis and coordinate immune responses. In cases of ER+ breast cancer, peripheral immune cells exhibit altered responses to several cytokines, and these alterations are correlated strongly with patient outcomes. To develop a systems-level understanding of this dysregulation, we measured a panel of cytokine responses and receptor abundances in the peripheral blood of healthy controls and ER+ breast cancer patients across immune cell types. Using tensor factorization to model this multidimensional data, we found that breast cancer patients exhibited widespread alterations in response, including drastically reduced response to IL-10 and heightened basal levels of pSmad2/3 and pSTAT4. ER+ patients also featured upregulation of PD-L1, IL6Rα, and IL2Rα, among other receptors. Despite this, alterations in response to cytokines were not explained by changes in receptor abundances. Thus, tensor factorization helped to reveal a coordinated reprogramming of the immune system that was consistent across our cohort.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Systems immunology approaches to study T cells in health and disease. 用系统免疫学方法研究健康和疾病中的 T 细胞。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2024-10-09 DOI: 10.1038/s41540-024-00446-1

Aaron Yang, Amanda C Poholek

引用次数: 0

YAP/TAZ drives Notch and angiogenesis mechanoregulation in silico. YAP/TAZ在硅学中驱动Notch和血管生成机械调节。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2024-10-05 DOI: 10.1038/s41540-024-00444-3

Margot Passier, Katie Bentley, Sandra Loerakker, Tommaso Ristori

{"title":"YAP/TAZ drives Notch and angiogenesis mechanoregulation in silico.","authors":"Margot Passier, Katie Bentley, Sandra Loerakker, Tommaso Ristori","doi":"10.1038/s41540-024-00444-3","DOIUrl":"10.1038/s41540-024-00444-3","url":null,"abstract":"Endothelial cells are key players in the cardiovascular system. Among other things, they are responsible for sprouting angiogenesis, the process of new blood vessel formation essential for both health and disease. Endothelial cells are strongly regulated by the juxtacrine signaling pathway Notch. Recent studies have shown that both Notch and angiogenesis are influenced by extracellular matrix stiffness; however, the underlying mechanisms are poorly understood. Here, we addressed this challenge by combining computational models of Notch signaling and YAP/TAZ, stiffness- and cytoskeleton-regulated mechanotransducers whose activity inhibits both Dll4 (Notch ligand) and LFng (Notch-Dll4 binding modulator). Our simulations successfully mimicked previous experiments, indicating that this YAP/TAZ-Notch crosstalk elucidates the Notch and angiogenesis mechanoresponse to stiffness. Additional simulations also identified possible strategies to control Notch activity and sprouting angiogenesis via cytoskeletal manipulations or spatial patterns of alternating stiffnesses. Our study thus inspires new experimental avenues and provides a promising modeling framework for further investigations into the role of Notch, YAP/TAZ, and mechanics in determining endothelial cell behavior during angiogenesis and similar processes.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11455968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Peptide hemolytic activity analysis using visual data mining of similarity-based complex networks. 利用基于相似性的复杂网络的可视化数据挖掘进行多肽溶血活性分析。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2024-10-04 DOI: 10.1038/s41540-024-00429-2

Kevin Castillo-Mendieta, Guillermin Agüero-Chapin, Edgar A Marquez, Yunierkis Perez-Castillo, Stephen J Barigye, Nelson Santiago Vispo, Cesar R García-Jacas, Yovani Marrero-Ponce

{"title":"Peptide hemolytic activity analysis using visual data mining of similarity-based complex networks.","authors":"Kevin Castillo-Mendieta, Guillermin Agüero-Chapin, Edgar A Marquez, Yunierkis Perez-Castillo, Stephen J Barigye, Nelson Santiago Vispo, Cesar R García-Jacas, Yovani Marrero-Ponce","doi":"10.1038/s41540-024-00429-2","DOIUrl":"10.1038/s41540-024-00429-2","url":null,"abstract":"Peptides are promising drug development frameworks that have been hindered by intrinsic undesired properties including hemolytic activity. We aim to get a better insight into the chemical space of hemolytic peptides using a novel approach based on network science and data mining. Metadata networks (METNs) were useful to characterize and find general patterns associated with hemolytic peptides, whereas Half-Space Proximal Networks (HSPNs), represented the hemolytic peptide space. The best candidate HSPNs were used to extract various subsets of hemolytic peptides (scaffolds) considering network centrality and peptide similarity. These scaffolds have been proved to be useful in developing robust similarity-based model classifiers. Finally, using an alignment-free approach, we reported 47 putative hemolytic motifs, which can be used as toxic signatures when developing novel peptide-based drugs. We provided evidence that the number of hemolytic motifs in a sequence might be related to the likelihood of being hemolytic.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Network modeling links kidney developmental programs and the cancer type-specificity of VHL mutations. 网络模型将肾脏发育程序与 VHL 突变的癌症类型特异性联系起来。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2024-10-03 DOI: 10.1038/s41540-024-00445-2

Xiaobao Dong, Donglei Zhang, Xian Zhang, Yun Liu, Yuanyuan Liu

{"title":"Network modeling links kidney developmental programs and the cancer type-specificity of VHL mutations.","authors":"Xiaobao Dong, Donglei Zhang, Xian Zhang, Yun Liu, Yuanyuan Liu","doi":"10.1038/s41540-024-00445-2","DOIUrl":"10.1038/s41540-024-00445-2","url":null,"abstract":"Elucidating the molecular dependencies behind the cancer-type specificity of driver mutations may reveal new therapeutic opportunities. We hypothesized that developmental programs would impact the transduction of oncogenic signaling activated by a driver mutation and shape its cancer-type specificity. Therefore, we designed a computational analysis framework by combining single-cell gene expression profiles during fetal organ development, latent factor discovery, and information theory-based differential network analysis to systematically identify transcription factors that selectively respond to driver mutations under the influence of organ-specific developmental programs. After applying this approach to VHL mutations, which are highly specific to clear cell renal cell carcinoma (ccRCC), we revealed important regulators downstream of VHL mutations in ccRCC and used their activities to cluster patients with ccRCC into three subtypes. This classification revealed a more significant difference in prognosis than the previous mRNA profile-based method and was validated in an independent cohort. Moreover, we found that EP300, a key epigenetic factor maintaining the regulatory network of the subtype with the worst prognosis, can be targeted by a small inhibitor, suggesting a potential treatment option for a subset of patients with ccRCC. This work demonstrated an intimate relationship between organ development and oncogenesis from the perspective of systems biology, and the method can be generalized to study the influence of other biological processes on cancer driver mutations.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

A web portal for exploring kinase-substrate interactions. 探索激酶-底物相互作用的门户网站。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2024-10-03 DOI: 10.1038/s41540-024-00442-5

John A P Sekar, Yan Chak Li, Avner Schlessinger, Gaurav Pandey

{"title":"A web portal for exploring kinase-substrate interactions.","authors":"John A P Sekar, Yan Chak Li, Avner Schlessinger, Gaurav Pandey","doi":"10.1038/s41540-024-00442-5","DOIUrl":"10.1038/s41540-024-00442-5","url":null,"abstract":"Interactions between protein kinases and their substrates are critical for the modulation of complex signaling pathways. Currently, there is a large amount of information available about kinases and their substrates in disparate public databases. However, these data are difficult to interpret in the context of cellular systems, which can be facilitated by examining interactions among multiple proteins at once, such as the network of interactions that constitute a signaling pathway. We present KiNet, a user-friendly web portal that integrates and shares information about kinase-substrate interactions from multiple databases of post-translational modifications. KiNet enables the visual exploration of these interactions in systems contexts, such as pathways, domain families, and custom protein set inputs, in an interactive fashion. We expect KiNet to be useful as a knowledge discovery tool for kinase-substrate interactions, and the aggregated KiNet dataset to be useful for protein kinase studies and systems-level analyses. The portal is available at https://kinet.kinametrix.com/ .","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11450209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Calibrating tumor growth and invasion parameters with spectral spatial analysis of cancer biopsy tissues. 利用癌症活检组织的光谱空间分析校准肿瘤生长和侵袭参数。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2024-10-02 DOI: 10.1038/s41540-024-00439-0

Stefano Pasetto, Michael Montejo, Mohammad U Zahid, Marilin Rosa, Robert Gatenby, Pirmin Schlicke, Roberto Diaz, Heiko Enderling

引用次数: 0

Inertial effect of cell state velocity on the quiescence-proliferation fate decision. 细胞状态速度对静止-增殖命运决定的惯性效应

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2024-10-02 DOI: 10.1038/s41540-024-00428-3

Harish Venkatachalapathy, Cole Brzakala, Eric Batchelor, Samira M Azarin, Casim A Sarkar

{"title":"Inertial effect of cell state velocity on the quiescence-proliferation fate decision.","authors":"Harish Venkatachalapathy, Cole Brzakala, Eric Batchelor, Samira M Azarin, Casim A Sarkar","doi":"10.1038/s41540-024-00428-3","DOIUrl":"10.1038/s41540-024-00428-3","url":null,"abstract":"Energy landscapes can provide intuitive depictions of population heterogeneity and dynamics. However, it is unclear whether individual cell behavior, hypothesized to be determined by initial position and noise, is faithfully recapitulated. Using the p21-/Cdk2-dependent quiescence-proliferation decision in breast cancer dormancy as a testbed, we examined single-cell dynamics on the landscape when perturbed by hypoxia, a dormancy-inducing stress. Combining trajectory-based energy landscape generation with single-cell time-lapse microscopy, we found that a combination of initial position and velocity on a p21/Cdk2 landscape, but not position alone, was required to explain the observed cell fate heterogeneity under hypoxia. This is likely due to additional cell state information such as epigenetic features and/or other species encoded in velocity but missing in instantaneous position determined by p21 and Cdk2 levels alone. Here, velocity dependence manifested as inertia: cells with higher cell cycle velocities prior to hypoxia continued progressing along the cell cycle under hypoxia, resisting the change in landscape towards cell cycle exit. Such inertial effects may markedly influence cell fate trajectories in tumors and other dynamically changing microenvironments where cell state transitions are governed by coordination across several biochemical species.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Neutral evolution of rare cancer mutations in the computer and the clinic. 计算机和临床中罕见癌症突变的中性演化。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2024-10-02 DOI: 10.1038/s41540-024-00436-3

Robert A Beckman

引用次数: 0