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

Molecular noise modulates transitions in the cell-fate differentiation landscape. 分子噪声调节细胞命运分化景观的转变。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-06-21 DOI: 10.1038/s41540-026-00762-8

Yujing Liu, Adriana Zanca, Michael P H Stumpf, Lucy Ham

{"title":"Molecular noise modulates transitions in the cell-fate differentiation landscape.","authors":"Yujing Liu, Adriana Zanca, Michael P H Stumpf, Lucy Ham","doi":"10.1038/s41540-026-00762-8","DOIUrl":"10.1038/s41540-026-00762-8","url":null,"abstract":"Waddington's epigenetic landscape has become one of biology's cornerstone metaphors, widely used both conceptually and computationally. Cell types are often associated with the qualitatively stable points or valleys of this landscape. In previous work, we showed that the molecular noise dominating sub-cellular dynamics can distort and profoundly reshape this landscape. In non-equilibrium systems, an equally profound question arises: to what extent does noise alter the transition paths between valleys in such dynamic landscapes? We tackle this question using a set of illustrative exemplars and show that noise gives rise to paths that differ substantially from the canonical least-action paths calculated under deterministic dynamics. We dissect the dynamics of these exemplars and determine the reactive density and transition currents, which show us, respectively, where and how transitions occur for different realizations of stochastic dynamics. Our analysis unambiguously demonstrates that reaction paths for stochastic dynamics diverge non-trivially from their deterministic least-action paths or simple barrier crossing models.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13646251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148295856","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

Pathway-centric visualization of cell-cell communication in single-cell transcriptomics data. 单细胞转录组学数据中细胞-细胞通讯的通路中心可视化。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-06-20 DOI: 10.1038/s41540-026-00768-2

Sidrah Maryam, Martin Manolov, Rafael Kramann, Sikander Hayat

引用次数: 0

Growth rate-dependent mutations and phenotypic switching facilitate rapid adaptation. 生长速率相关的突变和表型转换促进了快速适应。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-06-16 DOI: 10.1038/s41540-026-00758-4

Anton Grishechkin, Omer Karin

{"title":"Growth rate-dependent mutations and phenotypic switching facilitate rapid adaptation.","authors":"Anton Grishechkin, Omer Karin","doi":"10.1038/s41540-026-00758-4","DOIUrl":"10.1038/s41540-026-00758-4","url":null,"abstract":"The mutation rates of many species are regulated in response to internal and external conditions. Studies in several model organisms have shown that mutation rates can be modulated by the organism's growth rate, particularly through stress-induced mutagenesis. Here, we investigate the functional consequences of this coupling. Using a model of asexual evolution on a high-dimensional, single-peaked fitness landscape, we show that regulating mutation rate through growth rate provides an efficient strategy for rapid adaptation. This mechanism maximizes growth by balancing mutation and selection pressures. We approximate the optimal coupling as a biphasic response function that prescribes a low, constant mutation rate at high growth rates, which gradually increases once growth falls below a critical threshold. This adaptive strategy depends on two key parameters: mutational gain and critical growth rate, both determined by environmental conditions. This raises the question of how organisms establish these parameters in fluctuating environments. We demonstrate that weak selection in well-adapted populations, combined with long-term phenotypic fluctuations, can generate variability in these parameters. Such standing variation prepares populations for rapid evolution following environmental change. Our findings connect this adaptive strategy to specific molecular regulatory circuits and provide predictions for sequential antibiotic treatment regimens.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265322","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

Intelligent tool orchestration for rapid mechanistic model prototyping: MCP servers as AI-biology interfaces. 用于快速机械模型原型的智能工具编排：作为ai -生物学接口的MCP服务器。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-06-15 DOI: 10.1038/s41540-026-00767-3

Marco Ruscone, Miguel Vazquez, Alfonso Valencia

{"title":"Intelligent tool orchestration for rapid mechanistic model prototyping: MCP servers as AI-biology interfaces.","authors":"Marco Ruscone, Miguel Vazquez, Alfonso Valencia","doi":"10.1038/s41540-026-00767-3","DOIUrl":"10.1038/s41540-026-00767-3","url":null,"abstract":"Constructing multicellular mechanistic models traditionally requires extensive time and computational expertise. We introduce intelligent tool orchestration via Model Context Protocol (MCP) servers, enabling Large Language Model (LLM) agents to act as AI laboratory assistants for rapid model prototyping. We demonstrate this approach by constructing a multiscale model of cancer cell fate in response to TNF using an AI agent connected to MCP servers interfacing with three complementary tools: NeKo for gene regulatory networks construction, MaBoSS for Boolean models simulation, and PhysiCell for setting up multicellular agent-based models. This workflow was executed entirely through natural language interactions, without manual coding, direct parameter editing, or manual modification of generated model files. Through this use case, we identified key principles for biological AI-tool integration, specifically regarding tool granularity, session management, and flexible orchestration. Testing across multiple LLMs demonstrated our framework's portability, though model-dependent variations emphasize the need for rigorous validation. Ultimately, this work establishes a foundation for AI-assisted rapid prototyping, enabling researchers to explore computational hypotheses more rapidly through natural language interaction.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258963","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

Spatial analysis of malignant-immune cell interactions in the tumor microenvironment using topological data analysis. 利用拓扑数据分析肿瘤微环境中恶性免疫细胞相互作用的空间分析。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-06-13 DOI: 10.1038/s41540-026-00763-7

Seol Ah Park, Davide Gurnari, Paweł Dłotko, Yongsoo Kim, Jooyoung Hahn

{"title":"Spatial analysis of malignant-immune cell interactions in the tumor microenvironment using topological data analysis.","authors":"Seol Ah Park, Davide Gurnari, Paweł Dłotko, Yongsoo Kim, Jooyoung Hahn","doi":"10.1038/s41540-026-00763-7","DOIUrl":"10.1038/s41540-026-00763-7","url":null,"abstract":"The spatial interactions between malignant and immune cells in the tumor microenvironment are important for tumor immunobiology and patient outcomes. However, analytical tools that can extract rigorous yet interpretable spatial features and link them to patient outcomes remain limited. We propose a framework integrating TDA with statistical approaches to extract interpretable spatial features characterizing malignant-immune interactions. We introduce Topological Malignant Region (TopMR), which uses topological persistence to automatically define regions of malignant cells, providing an objective reference for spatial analysis even when tumor boundaries are ambiguous. Global-scale infiltration is quantified using signed distances from immune cells to the TopMR boundary and local-scale interactions are captured via malignant cell density around individual immune cells. These global and local features are integrated into a unified signed distance-density ( <math><mrow><mi>s</mi> <mi>DD</mi></mrow> </math> ) space, enabling comprehensive characterization of spatial patterns. We apply this framework to high-resolution multiplex immunofluorescence images of diffuse large B-cell lymphoma, analyzing both malignant-enriched and tumor border regions. Two-stage hierarchical clustering stratifies patients based on spatial interaction patterns, revealing associations with survival outcomes. This framework provides an end-to-end pipeline from spatial feature extraction to clinical interpretation, suggesting how region-aware spatial analysis can capture biologically meaningful patterns linked to patient survival.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240045","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

Determining parameter impact in systems biology models via sensitivity analysis: a comparative approach. 通过敏感性分析确定系统生物学模型中的参数影响：一种比较方法。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-06-13 DOI: 10.1038/s41540-026-00757-5

Kelsey I Gasior

{"title":"Determining parameter impact in systems biology models via sensitivity analysis: a comparative approach.","authors":"Kelsey I Gasior","doi":"10.1038/s41540-026-00757-5","DOIUrl":"10.1038/s41540-026-00757-5","url":null,"abstract":"Mathematical modeling is a powerful tool to understand biological phenomena, predict behavior, and guide experiments. Model parameters represent experimentally derived rates, and it can be challenging to understand how parameters affect the system's output(s). Global sensitivity analysis (GSA) can help determine how uncertainty in model outcomes can be attributed to parameters. Methods like Sobol' indices provide detailed analysis but at a high computational cost. Thus, it may be necessary to precede it by another method to reduce the parameter space. Morris Method Screening (MMS) is a qualitative analysis that can provide information about sensitivity and parameter interactions, making it a good partner for Sobol'. Partial Rank Correlation Coefficient (PRCC) may also be a viable option as it has a similar cost to MMS. This work tests whether a ranking (PRCC) or screening (MMS) method is better when used in combination with Sobol' analysis. Using a model of the epithelial-mesenchymal transition as a test case, this work shows that PRCC-Sobol' and MMS-Sobol' can produce diverging results, making it difficult to analyze how biological events are informed by specific rates and quantities. However, the differences between these methods mean that these techniques may be most effective when all three are used together.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13623827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252536","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 powerful representation learning method for enhanced analysis of incomplete multi-omics data. 一种强大的表示学习方法，用于增强不完整多组学数据的分析。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-06-11 DOI: 10.1038/s41540-026-00759-3

Jenna L Ballard, Zongyu Dai, Li Shen, Qi Long

引用次数: 0

Longitudinal spatial neutrophil profiling during ACT in murine melanoma reveals distinct lymph node infiltration patterns. 小鼠黑色素瘤ACT期间的纵向空间中性粒细胞谱显示明显的淋巴结浸润模式。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-06-11 DOI: 10.1038/s41540-026-00765-5

Gemma van der Voort, Maike Effern, Michelle C R Yong, Lukas Kiwitz, Roberta Turiello, Sonia Leonardelli, Susanna Ng, Dillon Corvino, Tobias Bald, Nicole Glodde, Kevin Thurley, Jan Hasenauer, Michael Hölzel

{"title":"Longitudinal spatial neutrophil profiling during ACT in murine melanoma reveals distinct lymph node infiltration patterns.","authors":"Gemma van der Voort, Maike Effern, Michelle C R Yong, Lukas Kiwitz, Roberta Turiello, Sonia Leonardelli, Susanna Ng, Dillon Corvino, Tobias Bald, Nicole Glodde, Kevin Thurley, Jan Hasenauer, Michael Hölzel","doi":"10.1038/s41540-026-00765-5","DOIUrl":"10.1038/s41540-026-00765-5","url":null,"abstract":"Reactive neutrophil infiltration can restrain CD8+ T cell expansion in lymph nodes during adoptive T cell therapy (ACT), yet its spatiotemporal regulation remains incompletely understood. Levaraging flow cytometry and multiplex immunofluorescence data, we performed a time-resolved quantitative assessment of immune cell dynamics in tumor-draining lymph node (tdLN) and non-tumor-draining lymph node (non-tdLN) in a melanoma mouse model receiving ACT. Transferred tumor-reactive CD8+ T cells accumulated and expanded early after treatment initiation, showing the highest frequency of a favorable central memory 13 CD8+ T cell phenotype in the tdLN. Enhancing innate immune signaling in melanomas increased neutrophil influx into lymph nodes, particularly the non-tdLN; however, within the tdLN, neutrophils were enriched in the T cell zone, which also contained the largest absolute reservoir of transferred CD8+ T cells. Together, these findings indicate that tdLN and non-tdLN differ in early neutrophil dynamics and compartmentalization during ACT, influenced by the strength of innate immune signaling in the tumor.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"12 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13261029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148227016","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

Integrating imaging and mathematical modeling to predict and optimize patient outcomes in oncology. 整合影像学和数学模型来预测和优化肿瘤患者的预后。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-06-10 DOI: 10.1038/s41540-026-00764-6

Reshmi J S Patel, Ayesha Das, Aliya Anil, Gauri Patel, Ryan T Woodall, Chase Christenson, Tarini Thiagarajan, Ernesto A B F Lima, Guillermo Lorenzo, David A Hormuth, Russell C Rockne, Vikram Adhikarla, Chengyue Wu, Thomas E Yankeelov

引用次数: 0

Hyperpathway: visualizing organization of pathway-molecule enriched interactions in omics studies via hyperbolic bipartite network embedding. 超通路：通过双曲二部网络嵌入来可视化组学研究中通路-分子富集相互作用的组织。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-06-09 DOI: 10.1038/s41540-026-00752-w

Ilyes Abdelhamid, Ziheng Liao, Yuchi Liu, Armel Lefebvre, Aldo Acevedo, Carlo Vittorio Cannistraci

{"title":"Hyperpathway: visualizing organization of pathway-molecule enriched interactions in omics studies via hyperbolic bipartite network embedding.","authors":"Ilyes Abdelhamid, Ziheng Liao, Yuchi Liu, Armel Lefebvre, Aldo Acevedo, Carlo Vittorio Cannistraci","doi":"10.1038/s41540-026-00752-w","DOIUrl":"10.1038/s41540-026-00752-w","url":null,"abstract":"Pathway enrichment analysis (PEA) of omics data identifies significant pathway-molecule associations, yet delivers results as tabular lists in which complex systems-biology insights remain inaccessible. Hyperpathway is an open-access network-based webtool that addresses this limitation through three original innovations: (1) conversion of a PEA results table into a pathway-molecule bipartite network; (2) a minimal artificial linking strategy to resolve structural disconnections; (3) a leaf removal and post-hoc reinsertion pipeline that accelerates coalescent embedding without any loss of geometric fidelity. The resulting network is visualized in a two-dimensional hyperbolic disk with flexible coloring schemes encoding hierarchical relevance, connectivity similarity, statistical significance, or user-defined annotations; revealing latent functional modules that are invisible in conventional tabular outputs. Validated on genomic, metabolomic, and lipidomic datasets, Hyperpathway enables a deeper, systems-level understanding of the interplay between pathways and their molecular components, providing insights that go beyond p-value-based significance testing. Beyond PEA, Hyperpathway can be used as a general-purpose open webtool for fast hyperbolic embedding and interactive visualization of any bipartite network.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148205570","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