NPJ Systems Biology and Applications最新文献_第4页

Bringing evolutionary cancer therapy to the clinic: a systems approach. 将进化癌症疗法引入临床：系统方法。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2025-05-27 DOI: 10.1038/s41540-025-00528-8

Arina Soboleva, Irene Grossmann, Anne-Marie C Dingemans, Jafar Rezaei, Kateřina Staňková

引用次数: 0

Model of metabolism and gene expression predicts proteome allocation in Pseudomonas putida. 代谢和基因表达模型预测恶臭假单胞菌蛋白质组分配。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2025-05-24 DOI: 10.1038/s41540-025-00521-1

Juan D Tibocha-Bonilla, Vishant Gandhi, Chloe Lieng, Oriane Moyne, Rodrigo Santibáñez-Palominos, Karsten Zengler

{"title":"Model of metabolism and gene expression predicts proteome allocation in Pseudomonas putida.","authors":"Juan D Tibocha-Bonilla, Vishant Gandhi, Chloe Lieng, Oriane Moyne, Rodrigo Santibáñez-Palominos, Karsten Zengler","doi":"10.1038/s41540-025-00521-1","DOIUrl":"10.1038/s41540-025-00521-1","url":null,"abstract":"The genome-scale model of metabolism and gene expression (ME-model) for Pseudomonas putida KT2440, iPpu1676-ME, provides a comprehensive representation of biosynthetic costs and proteome allocation. Compared to a metabolic-only model, iPpu1676-ME significantly expands on gene expression, macromolecular assembly, and cofactor utilization, enabling accurate growth predictions without additional constraints. Multi-omics analysis using RNA sequencing and ribosomal profiling data revealed translational prioritization in P. putida, with core pathways, such as nicotinamide biosynthesis and queuosine metabolism, exhibiting higher translational efficiency, while secondary pathways displayed lower priority. Notably, the ME-model significantly outperformed the M-model in alignment with multi-omics data, thereby validating its predictive capacity. Thus, iPpu1676-ME offers valuable insights into P. putida's proteome allocation and presents a powerful tool for understanding resource allocation in this industrially relevant microorganism.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"11 1","pages":"55"},"PeriodicalIF":3.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143115","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

Personalizing neoadjuvant chemotherapy regimens for triple-negative breast cancer using a biology-based digital twin. 使用基于生物学的数字双胞胎个性化三阴性乳腺癌新辅助化疗方案。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2025-05-23 DOI: 10.1038/s41540-025-00531-z

Chase Christenson, Chengyue Wu, David A Hormuth, Jingfei Ma, Clinton Yam, Gaiane M Rauch, Thomas E Yankeelov

{"title":"Personalizing neoadjuvant chemotherapy regimens for triple-negative breast cancer using a biology-based digital twin.","authors":"Chase Christenson, Chengyue Wu, David A Hormuth, Jingfei Ma, Clinton Yam, Gaiane M Rauch, Thomas E Yankeelov","doi":"10.1038/s41540-025-00531-z","DOIUrl":"10.1038/s41540-025-00531-z","url":null,"abstract":"Despite advances triple negative breast cancer treatment, ~50% of patients will not achieve a pathological complete response prior to surgery with standard of care neoadjuvant therapy (NAT). We hypothesize that personalized regimens for NAT could significantly improve patient outcomes, which we address with a patient-specific digital twin framework. This framework is established by calibrating a biology-based model to longitudinal magnetic resonance images with approximate Bayesian computation. We then apply optimal control theory to either (1) reduce the final tumor cell number with equivalent dose, or (2) reduce the total dose of NAT with equivalent response. For (1), the personalized regimens (n = 50) achieved a median (range) reduction in the final tumor cell number of 17.62% (0.00-37.36%). For (2), the personalized regimens achieved a median reduction in dose delivered of 12.62% (0.00-56.55%) when compared to the standard-of-care regimen, while providing statistically equivalent tumor control.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"11 1","pages":"53"},"PeriodicalIF":3.5,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132642","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

Estimating treatment sensitivity in synthetic and in vitro tumors using a random differential equation model. 用随机微分方程模型估计合成肿瘤和体外肿瘤的治疗敏感性。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2025-05-23 DOI: 10.1038/s41540-025-00530-0

Natalie Meacham, Erica M Rutter

引用次数: 0

Emergence of multiple collective motility modes in a physical model of cell chains. 在细胞链的物理模型中出现了多种集体运动模式。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2025-05-22 DOI: 10.1038/s41540-025-00529-7

Ying Zhang, Effie E Bastounis, Calina Copos

{"title":"Emergence of multiple collective motility modes in a physical model of cell chains.","authors":"Ying Zhang, Effie E Bastounis, Calina Copos","doi":"10.1038/s41540-025-00529-7","DOIUrl":"10.1038/s41540-025-00529-7","url":null,"abstract":"Collective cell migration is central to processes like development and cancer metastasis. While mechanisms of collective motility are increasingly understood, their classification remains incomplete. Here, we study the migration of small cell chains, namely cohesive pairs. Experiments with Dictyostelium discoideum (Dd) revealed two motility modes: the individual contributor (IC) mode, where each cell generates its own traction dipole, and the supracellular (S) mode, characterized by a single dipole. Dd pairs favored the IC mode, while Madin-Darby canine kidney (MDCK) doublets predominantly used the S mode. A 2D biophysical model recapitulated many experimental observations; the IC mode emerged naturally in ameboid Dd doublets when both cells exerted similar traction stresses, while the S mode dominated with stronger leaders. Contrary to amebas, MDCK-like cell chains showed a bias towards the IC mode when increasing cell-cell adhesion. Extending the model to longer chains, we show its potential for understanding emergent migration patterns across cell types and scales.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"11 1","pages":"52"},"PeriodicalIF":3.5,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12098859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127713","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

COmmunity and Single Microbe Optimisation System (COSMOS). 群落和单一微生物优化系统（COSMOS）。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2025-05-21 DOI: 10.1038/s41540-025-00534-w

Lavanya Raajaraam, Karthik Raman

{"title":"COmmunity and Single Microbe Optimisation System (COSMOS).","authors":"Lavanya Raajaraam, Karthik Raman","doi":"10.1038/s41540-025-00534-w","DOIUrl":"10.1038/s41540-025-00534-w","url":null,"abstract":"Bioprocessing utilises microbial monocultures and communities to convert renewable resources into valuable products. While monocultures offer simplicity, communities provide metabolic diversity and cooperative biosynthesis. To systematically evaluate these systems, we developed COmmunity and Single Microbe Optimisation System (COSMOS), a dynamic computational framework that simulates and compares monocultures and co-cultures to determine optimal microbial systems tailored to a specific environment. COSMOS revealed key factors shaping biosynthetic performance, such as environmental conditions, microbial interactions, and carbon sources. Notably, it predicted the Shewanella oneidensis-Klebsiella pneumoniae co-culture as the most efficient producer of 1,3-propanediol under anaerobic conditions, aligning closely with experimental data, including optimal carbon source concentrations and inoculum ratios. Additional findings highlight the resilience of microbial communities in nutrient-limited processes and emphasise the role of computational tools in balancing productivity with operational simplicity. Overall, this study advances the rational design of microbial systems, paving the way for sustainable bioprocesses and circular bio-economies.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"11 1","pages":"51"},"PeriodicalIF":3.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120191","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

Genome-scale metabolic modelling identifies reactions mediated by SNP-SNP interactions associated with yeast sporulation. 基因组尺度的代谢模型鉴定了与酵母产孢相关的SNP-SNP相互作用介导的反应。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2025-05-20 DOI: 10.1038/s41540-025-00503-3

Srijith Sasikumar, S Pavan Kumar, Nirav Pravinbhai Bhatt, Himanshu Sinha

{"title":"Genome-scale metabolic modelling identifies reactions mediated by SNP-SNP interactions associated with yeast sporulation.","authors":"Srijith Sasikumar, S Pavan Kumar, Nirav Pravinbhai Bhatt, Himanshu Sinha","doi":"10.1038/s41540-025-00503-3","DOIUrl":"10.1038/s41540-025-00503-3","url":null,"abstract":"Genome-scale metabolic models (GEMs) are powerful tools used to understand the functional effects of genetic variants. However, the impact of single nucleotide polymorphisms (SNPs) in transcription factors and their interactions on metabolic fluxes remains largely unexplored. Using gene expression data from a yeast allele replacement panel grown during sporulation, we constructed co-expression networks and SNP-specific GEMs. Analysis of co-expression networks revealed that during sporulation, SNP-SNP interactions impact the connectivity of metabolic regulators involved in glycolysis, steroid and histidine biosynthesis, and amino acid metabolism. Further, genome-scale differential flux analysis identified reactions within six major metabolic pathways associated with sporulation efficiency variation. Notably, autophagy was predicted to act as a pentose pathway-dependent compensatory mechanism supplying critical precursors like nucleotides and amino acids, enhancing sporulation. Our study highlights how transcription factor polymorphisms interact to shape metabolic pathways in yeast, offering insights into genetic variants associated with metabolic traits in genome-wide association studies.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"11 1","pages":"50"},"PeriodicalIF":3.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111532","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

SEgene identifies links between super enhancers and gene expression across cell types. SEgene识别超级增强子和跨细胞类型的基因表达之间的联系。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2025-05-19 DOI: 10.1038/s41540-025-00533-x

Norio Shinkai, Ken Asada, Hidenori Machino, Ken Takasawa, Satoshi Takahashi, Nobuji Kouno, Masaaki Komatsu, Ryuji Hamamoto, Syuzo Kaneko

{"title":"SEgene identifies links between super enhancers and gene expression across cell types.","authors":"Norio Shinkai, Ken Asada, Hidenori Machino, Ken Takasawa, Satoshi Takahashi, Nobuji Kouno, Masaaki Komatsu, Ryuji Hamamoto, Syuzo Kaneko","doi":"10.1038/s41540-025-00533-x","DOIUrl":"10.1038/s41540-025-00533-x","url":null,"abstract":"Enhancers are non-coding DNA regions that facilitate gene transcription, with a specialized subset, super-enhancers, known to exert exceptionally strong transcriptional activation effects. Super-enhancers have been implicated in oncogenesis, and their identification is achievable through histone mark chromatin immunoprecipitation followed by sequencing data using existing analytical tools. However, conventional super-enhancer detection methodologies often do not accurately reflect actual gene expression levels, and the large volume of identified super-enhancers complicates comprehensive analysis. To address these limitations, we developed the super-enhancer to gene links (SE-to-gene Links) analysis, a platform named \"SEgene\" which incorporates the peak-to-gene links approach-a statistical method designed to reveal correlations between genes and peak regions ( https://github.com/hamamoto-lab/SEgene ). This platform enables a targeted evaluation of super-enhancer regions in relation to gene expression, facilitating the identification of super-enhancers that are functionally linked to transcriptional activity. Here, we demonstrate the application of SE-to-gene Links analysis to public datasets, confirming its efficacy in accurately detecting super-enhancers and identifying functionally associated genes. Additionally, SE-to-gene Links analysis identified ERBB2 as a significant gene of interest in the lung adenocarcinoma dataset from the National Cancer Center Japan cohort, suggesting a potential impact across multiple patient samples. Thus, the SE-to-gene Links analysis provides an analytical tool for evaluating super-enhancers as potential therapeutic targets, supporting the identification of clinically significant super-enhancer regions and their functionally associated genes.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"11 1","pages":"49"},"PeriodicalIF":3.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12089303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102234","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

Cell populations simulated in silico within SimulCell accurately reproduce the behaviour of experimental cell cultures. 在SimulCell内用硅模拟的细胞群准确地再现了实验细胞培养的行为。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2025-05-17 DOI: 10.1038/s41540-025-00518-w

Elvira Toscano, Elena Cimmino, Angelo Boccia, Leandra Sepe, Giovanni Paolella

{"title":"Cell populations simulated in silico within SimulCell accurately reproduce the behaviour of experimental cell cultures.","authors":"Elvira Toscano, Elena Cimmino, Angelo Boccia, Leandra Sepe, Giovanni Paolella","doi":"10.1038/s41540-025-00518-w","DOIUrl":"10.1038/s41540-025-00518-w","url":null,"abstract":"In silico simulations are used to understand cell behaviour by means of different approaches and tools, which range from reproducing average population trends to building lattice-based models to, more recently, creating populations of individual cell agents whose mass, volume and morphology behave according to more or less precise rules and models. In this work, a new agent-based simulator, SimulCell, was conceived, developed and used to predict the behaviour of eukaryotic cell cultures while growing attached to a flat surface. The system, starting from time-lapse microscopy experiments, uses growth, proliferation and migration models to create synthetic populations closely resembling original cultures. Support for cell-cell and cell-environment interaction makes cell agents able to react to changes in medium composition and other events, such as physical damage or chemical modifications occurring in the culture plate. The simulator is accessible through a web application and generates data that can be shown as tables and graphs or exported for further analyses.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"11 1","pages":"48"},"PeriodicalIF":3.5,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086634","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

Assessing the impact of sampling bias on node centralities in synthetic and biological networks. 评估采样偏差对合成和生物网络中节点中心性的影响。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2025-05-15 DOI: 10.1038/s41540-025-00526-w

Ali Salehzadeh-Yazdi, Marc-Thorsten Hütt

{"title":"Assessing the impact of sampling bias on node centralities in synthetic and biological networks.","authors":"Ali Salehzadeh-Yazdi, Marc-Thorsten Hütt","doi":"10.1038/s41540-025-00526-w","DOIUrl":"10.1038/s41540-025-00526-w","url":null,"abstract":"Centrality measures are crucial for network analysis, offering insights into node importance within complex networks. However, their accuracy is often affected by observational errors and incomplete data. This study investigates how sampling biases systematically impact centrality measures. We simulate six types of biased down-sampling, transitioning networks from dense to sparse states, using the initial network as the 'ground truth.' Changes in centrality values reveal the robustness of these measures under various sampling scenarios across synthetic and biological networks. Our results show that in synthetic networks, some sampling methods consistently exhibit higher robustness, particularly in scale-free networks. For biological networks, protein interaction networks are the most robust, followed by metabolite, gene regulatory, and reaction networks. Local centrality measures generally show greater robustness, while global measures are more heterogeneous and less reliable. This study highlights the limitations of centrality measures under sampling biases and informs the development of more robust methodologies.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"11 1","pages":"47"},"PeriodicalIF":3.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079162","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