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

Th2 bias and T-cell exhaustion characterize the immunopathology of non-tuberculous mycobacterial pulmonary disease. Th2偏倚和t细胞耗竭是非结核性分枝杆菌肺病的免疫病理特征。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-07-07 DOI: 10.1038/s41540-026-00784-2

Tingting Fang, Feifei Yuan, Yu Chen, Shuang Wan, Na Li, Yuyan Ma, Qingqing Wang, Wenting Jin, Qing Miao, Lijuan Hu, Jue Pan, Donghe Li, Bijie Hu

{"title":"Th2 bias and T-cell exhaustion characterize the immunopathology of non-tuberculous mycobacterial pulmonary disease.","authors":"Tingting Fang, Feifei Yuan, Yu Chen, Shuang Wan, Na Li, Yuyan Ma, Qingqing Wang, Wenting Jin, Qing Miao, Lijuan Hu, Jue Pan, Donghe Li, Bijie Hu","doi":"10.1038/s41540-026-00784-2","DOIUrl":"https://doi.org/10.1038/s41540-026-00784-2","url":null,"abstract":"Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is an escalating global health concern with poorly defined immunological mechanisms, necessitating comprehensive profiling to guide therapeutic advances. We analyzed peripheral blood from 28 treatment-naïve NTM-PD patients (19 Mycobacterium avium complex, 9 Mycobacterium abscessus) and 27 matched controls using 42-marker mass cytometry (CyTOF) and Luminex multiplex assays. A random forest model identified predictive markers, while an in vitro murine macrophage model evaluated chemokine production. NTM-PD patients displayed significant immune shifts, including increased classical monocytes (CD14+ CD16-), reduced NKT-like cells (CD3+ CD56+), and elevated T-cell exhaustion markers (PD-1, TOX). This coincided with a Th1/Th2 balance shift characterized by heightened IL-13. Elevated IFN-γ-inducible chemokines CXCL9 and CXCL10 coexisted with this Th2-biased signature, indicating a complex, dysregulated inflammatory state. A model integrating immune-cell frequencies and cytokine profiles achieved robust diagnostic accuracy (AUC = 0.922) with prognostic potential. In vitro, NTM-infected macrophages produced substantial CXCL9 and CXCL10 levels relative to the LPS maximal activation benchmark, identifying them as a major cellular source. These findings propose an immunological framework wherein T-cell exhaustion and a Th2-biased microenvironment strongly correlate with NTM-PD pathogenesis. CXCL9, CXCL10, and IL-13 emerge as candidate therapeutic targets, while our predictive model offers a foundational approach for risk stratification.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of phillyrin as a PPAR-γ ligand through network pharmacology and molecular modeling. 通过网络药理学和分子模型鉴定茶树苷为PPAR-γ配体。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-07-06 DOI: 10.1038/s41540-026-00780-6

Ling Huang, Zhizheng Fang, Rongchun Han, Xiaohui Tong

{"title":"Identification of phillyrin as a PPAR-γ ligand through network pharmacology and molecular modeling.","authors":"Ling Huang, Zhizheng Fang, Rongchun Han, Xiaohui Tong","doi":"10.1038/s41540-026-00780-6","DOIUrl":"https://doi.org/10.1038/s41540-026-00780-6","url":null,"abstract":"Insulin resistance is a core pathological hallmark of metabolic syndromes like type 2 diabetes mellitus. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a classical therapeutic target for improving insulin sensitivity, yet the clinical utility of its synthetic agonists faces diverse adverse reactions. We previously showed that phillyrin, an important component of Forsythia suspensa, could improve insulin resistance in obesity. However, its direct molecular targets remain not fully understood. Herein, we adopted a combined in silico and experimental approach to determine whether phillyrin could function as a ligand of PPAR-γ. We implemented a multi-scale strategy integrating network pharmacology, molecular modeling, with experimental verification. Network pharmacology analysis was employed to predict system-level targets and pathways associated with phillyrin. Subsequently, molecular docking and molecular dynamics simulations were conducted using computational chemistry methods to characterize the binding mode, dynamic stability, and binding free energy (MM-GBSA) of phillyrin within the PPAR-γ ligand-binding domain. Finally, key computational predictions were experimentally validated in insulin-resistant 3T3-L1 adipocytes and in a high-fat diet-induced murine model of insulin resistance.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oncostatin M orchestrates collective epithelial migration via HIF1A activation. Oncostatin M通过HIF1A激活协调集体上皮迁移。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-07-06 DOI: 10.1038/s41540-026-00778-0

Ian C McLean, Sean M Gross, Tiera A Liby, Mark A Dane, Daniel S Derrick, Laura M Heiser

{"title":"Oncostatin M orchestrates collective epithelial migration via HIF1A activation.","authors":"Ian C McLean, Sean M Gross, Tiera A Liby, Mark A Dane, Daniel S Derrick, Laura M Heiser","doi":"10.1038/s41540-026-00778-0","DOIUrl":"10.1038/s41540-026-00778-0","url":null,"abstract":"Extracellular signals strongly influence cell behavior, yet the mechanisms by which specific ligands mediate changes in phenotype remain unclear. The cytokine Oncostatin M (OSM) regulates homeostasis, wound healing, inflammation, and cancer progression. We previously found that OSM induces collective cell migration (CCM), a process whereby cells move as cohesive units while retaining cell-cell contacts, in MCF10A mammary epithelial cells. Here, we investigated how OSM drives CCM by comparing its effects with those elicited by epidermal growth factor (EGF) and interferon gamma (IFNG), defining ligand-specific phenotypes and molecular networks. Integrative transcriptomic and proteomic analyses identified hypoxia-inducible factor-1 (HIF1A) and signal transducer and activator of transcription 3 (STAT3) as central regulators of OSM responses. Functional validation revealed that HIF1A drives transcriptional programs associated with hypoxia, metabolic reprogramming, and immune pathways. Complement signaling emerged as a downstream effector of HIF1A, and its inhibition disrupted OSM-induced clustering and CCM. These findings establish a mechanistic link between OSM signaling, HIF1A activation, and CCM, demonstrating how cytokine-driven transcriptional reprogramming coordinates epithelial cell migration. Analysis of public breast cancer data indicate that this pathway is active in human tumors and may contribute to tissue remodeling, repair, and metastasis.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Expanding the role of metabolism in whole plant models. 扩展代谢在整个植物模型中的作用。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-07-04 DOI: 10.1038/s41540-026-00773-5

Karuthedath Shaijal, Meera Joshi, Sanu Shameer

引用次数: 0

Modeling single nucleus microglia across species identifies immune pathways and therapeutic candidates in Alzheimer's disease. 跨物种单核小胶质细胞建模识别阿尔茨海默病的免疫途径和治疗候选。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-07-03 DOI: 10.1038/s41540-026-00775-3

Alexander Bergendorf, Jee Hyun Park, Brendan K Ball, Douglas K Brubaker

{"title":"Modeling single nucleus microglia across species identifies immune pathways and therapeutic candidates in Alzheimer's disease.","authors":"Alexander Bergendorf, Jee Hyun Park, Brendan K Ball, Douglas K Brubaker","doi":"10.1038/s41540-026-00775-3","DOIUrl":"10.1038/s41540-026-00775-3","url":null,"abstract":"Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory loss and behavioral changes. A pivotal influence on AD pathology is the dysregulation of microglia in the brain. Despite promising findings in mouse models, there are limitations to the translatable biological information across species due to differences in the physiology, timeline of disease, and human heterogeneity. To address these interspecies discrepancies, we developed a novel implementation of the Translatable Components Regression (TransComp-R) framework, which integrated microglial single-nucleus transcriptomic data to identify biological pathways in mice AD models predictive of human AD. We compared model variations with sparse and traditional principal component analysis (PCA), finding that standard PCA encoded more interpretable mouse PCs compared to sPCA despite limited differences in technical performance. Mouse PCs significantly differentiated human AD from control microglial cells in the BA41/42, BA6/8, hippocampus and entorhinal cortex brain regions. However, these PCs had limited separation of human AD from control microglia in the prefrontal cortex. Additionally, we identified gene signatures from FDA-approved drugs that correlated with significant mouse component loadings, including valproic-acid and calcifediol. This computational framework may support the discovery of cross-species disease similarities, including the identification of candidate pharmacological solutions that may translate across species.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metabolic set theory: a generalized model of microbial interactions. 代谢集理论：微生物相互作用的广义模型。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-07-01 DOI: 10.1038/s41540-026-00774-4

Jyoti Jyoti, Hannah Zoller, Wolfgang Zu Castell, Marc-Thorsten Hütt

引用次数: 0

Gene prioritization across ancestries uncovers distinct molecular pathophysiology and therapeutic landscape in polycystic ovary syndrome. 基因优先级跨祖先揭示多囊卵巢综合征不同的分子病理生理和治疗景观。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-06-27 DOI: 10.1038/s41540-026-00772-6

Sindhuja Rajavelu, Debojyoti De

{"title":"Gene prioritization across ancestries uncovers distinct molecular pathophysiology and therapeutic landscape in polycystic ovary syndrome.","authors":"Sindhuja Rajavelu, Debojyoti De","doi":"10.1038/s41540-026-00772-6","DOIUrl":"https://doi.org/10.1038/s41540-026-00772-6","url":null,"abstract":"Polycystic ovary syndrome (PCOS) is a highly prevalent and heterogeneous endocrine disorder affecting women of reproductive age, with substantial reproductive, metabolic, and long-term health consequences. While genome-wide association studies (GWAS) have identified multiple PCOS-associated loci across diverse populations, the functional interpretation of these predominantly non-coding variants and their translation into clinically actionable targets remain unresolved. Here, we present an integrative population-aware framework that systematically combines regulatory functional genomics, long-range chromatin interactions, genome-wide quantitative trait loci, and protein-protein interaction networks to prioritize effector genes underlying PCOS susceptibility. Applying this framework to East Asian and European populations, we demonstrate robust performance relative to existing approaches and uncover both shared and population-specific functions. Notably, our analyses reveal a predominant enrichment of metabolic dysregulation-associated pathways in East Asian PCOS, whereas European PCOS exhibits a stronger inflammatory and immune-related signature. These population-specific molecular phenotypes were further supported by transcriptomic data from PCOS patient samples. Importantly, integration of genetic evidence with a network-based approach enabled the identification of druggable targets lacking direct genetic cues. Collectively, our study provides mechanistic insight into the ethnic heterogeneity of PCOS and establishes a scalable strategy for genetically informed, population-specific therapeutic prioritization, advancing precision medicine approaches for women's health.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148339639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A mathematical model of folate-mediated one-carbon metabolism in Down syndrome. 唐氏综合征中叶酸介导的单碳代谢的数学模型。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-06-26 DOI: 10.1038/s41540-026-00760-w

Allison Piovesan, Diletta Poluzzi, Giuseppe Ramacieri, Chiara Locatelli, Francesca Antonaros, Beatrice Vione, Maria Caracausi, Maria Chiara Pelleri, Luca Marchetti

{"title":"A mathematical model of folate-mediated one-carbon metabolism in Down syndrome.","authors":"Allison Piovesan, Diletta Poluzzi, Giuseppe Ramacieri, Chiara Locatelli, Francesca Antonaros, Beatrice Vione, Maria Caracausi, Maria Chiara Pelleri, Luca Marchetti","doi":"10.1038/s41540-026-00760-w","DOIUrl":"https://doi.org/10.1038/s41540-026-00760-w","url":null,"abstract":"Down syndrome (DS), the most frequent human genetic disorder marked by an extra copy of chromosome 21 (Hsa21) or a portion thereof, leads to physical and cognitive impairments. Following the Lejeune work, researchers focused on a potential anomaly within the folate-mediated one-carbon metabolism (FOCM). Here, we present a FOCM model modified from a previous work with the incorporation of the enzyme cystathionine beta-synthase (CBS), whose encoding gene is located on Hsa21, coupled with the methionine input rate. Systematic perturbation of FOCM enzyme activity rates has been performed to explore possible in silico configurations to simulate the DS condition. The perturbed vs. unperturbed model-derived ratio concentrations of tetrahydrofolate, 5-formyl-tetrahydrofolate, 5-methyl-tetrahydrofolate, S-adenosyl-homocysteine, and S-adenosyl-methionine were compared with the known literature through various statistical approaches. After investigating public transcriptomic databases, the FTS (formate-tetrahydrofolate ligase) perturbation achieved the best overall score. Although the FTS encoding gene (MTHFD1) is not located on Hsa21, it was found to be overexpressed in the DS condition. In addition, an interesting correlation emerged with the PTG (phosphoribosylglycinamide formyltransferase) perturbation and the corresponding encoding gene (GART), located on Hsa21 and notably over-expressed in the DS condition. The model thus identifies key enzyme activities that warrant further investigation.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148339618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characterizing open-ended evolution through undecidability mechanisms in random Boolean networks. 通过随机布尔网络中的不可判定机制表征开放式进化。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-06-23 DOI: 10.1038/s41540-026-00770-8

Amahury J López-Díaz, Pedro Juan Rivera Torres, Gerardo L Febres, Carlos Gershenson

{"title":"Characterizing open-ended evolution through undecidability mechanisms in random Boolean networks.","authors":"Amahury J López-Díaz, Pedro Juan Rivera Torres, Gerardo L Febres, Carlos Gershenson","doi":"10.1038/s41540-026-00770-8","DOIUrl":"https://doi.org/10.1038/s41540-026-00770-8","url":null,"abstract":"Discrete dynamical models underpin systems biology, but we still lack substrate-agnostic diagnostics for identifying finite-horizon dynamical signatures that may be relevant to open-ended evolution (OEE), such as the recurrent production of novel phenotypic states rather than rapid settling or unstructured noise. We introduce a simple, model-independent metric, Ω, that summarizes the residence-time-weighted contribution of attractor cycle lengths across the sequence of recurrent episodes realized within a finite observation window. Ω is zero for single-attractor dynamics and also vanishes for pure novelty without recurrence, while increasing when trajectories repeatedly enter multiple persistent cyclic phenotypes. Using Random Boolean Networks (RBNs) as a controlled testbed, we compare classical Boolean dynamics with biologically motivated non-classical mechanisms (probabilistic context switching, annealed rule mutation, paraconsistent logic, modal necessary/possible gating, and quantum-inspired superposition/paired-state coupling) under homogeneous and heterogeneous updating schemes. Our results support the view that undecidability-adjacent, state-dependent mechanisms-implemented as probabilistic context switching, modal necessity/possibility gating, paraconsistent logic, or quantum-inspired correlated branching-are enabling conditions for sustained novelty. At the end of our manuscript we outline a practical extension of Ω to continuous/hybrid state spaces, positioning Ω as a portable proxy for OEE in biological modeling and a guide for engineering evolvable synthetic circuits.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Virtual twins and the future of human developmental biology. 虚拟双胞胎和人类发育生物学的未来。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-06-23 DOI: 10.1038/s41540-026-00771-7

Maria Abou Chakra, Nika Shakiba

引用次数: 0