NPJ Systems Biology and Applications最新文献_第3页

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":"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":"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672785/pdf/","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":"OA","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":"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654937/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A minimal mechanically consistent model of smoothly dividing disk-shaped cells. 平滑分裂的盘状细胞的最小机械一致性模型。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-06-23 DOI: 10.1038/s41540-026-00756-6

Lukas Hupe, Yoav G Pollack, Jonas Isensee, Aboutaleb Amiri, Ramin Golestanian, Philip Bittihn

{"title":"A minimal mechanically consistent model of smoothly dividing disk-shaped cells.","authors":"Lukas Hupe, Yoav G Pollack, Jonas Isensee, Aboutaleb Amiri, Ramin Golestanian, Philip Bittihn","doi":"10.1038/s41540-026-00756-6","DOIUrl":"10.1038/s41540-026-00756-6","url":null,"abstract":"Replication through cell division is one of the fundamental processes of life and a major driver of dynamics in systems ranging from bacterial colonies to embryogenesis, tissues and tumors. While regulation also shapes self-organization, many biologically relevant behaviors arise from a limited number of physical ingredients, and particle-based models have become a popular platform to investigate these emergent dynamics. However, incorporating division into such models often produces aberrant mechanical fluctuations that hinder meaningful analysis. Here, we introduce a minimal model ensuring mechanical consistency during cell division. Cells consist of two nodes, overlapping disks which separate during division, forming transient dumbbell shapes. Internal degrees of freedom, cell-cell interactions and equations of motion guarantee force continuity at all times, including during division, both for the dividing cell and its interaction partners, while allowing arbitrary anisotropic mobilities. As a benchmark, we also translate an established model of proliferating spherocylinders with similar dynamics into our theoretical framework. Numerical simulations demonstrate force continuity of the new disk cell model, quantify the improvements, and show agreement in terms of collective behaviors such as alignment and orientational order. We also demonstrate force extraction and a Voronoi-based interpretation in a confluent-tissue context-with a three-dimensional generalization in embryonic-like confinement. A reference implementation of the model in two and three dimensions is freely available as a Julia package based on InPartS.jl. Our model provides a framework for analyzing mechanical observables such as velocities and stresses, and can be readily extended with additional biological features.","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13309542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308873","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

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

Vitiligo Information Resource database v3. 白癜风信息资源数据库v3。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-06-22 DOI: 10.1038/s41540-026-00713-3

Abhishek Sengupta, Vishal Singh, Muskan Syed, Alakto Choudhury, Payal Gupta, Somesh Gupta, Priyanka Narad

{"title":"Vitiligo Information Resource database v3.","authors":"Abhishek Sengupta, Vishal Singh, Muskan Syed, Alakto Choudhury, Payal Gupta, Somesh Gupta, Priyanka Narad","doi":"10.1038/s41540-026-00713-3","DOIUrl":"10.1038/s41540-026-00713-3","url":null,"abstract":"Vitiligo is a multifaceted autoimmune skin disease characterized by the loss of epidermal melanocytes, yet its molecular basis remains poorly understood. To address the need for a specialized systems biology interface, we present VIRdb v3.0, an integrative database combining curated transcriptomics-based datasets with differentially expressed genes, a protein-protein interaction network highlighting regulatory hubs, and an enriched library of natural compounds and FDA-approved drugs targeting vitiligo-related proteins. The platform supports pathway enrichment, molecular docking, and cross-disease comparisons with autoimmune disorders to identify shared molecular signatures. Backend redevelopment using the Django framework enables scalability and real-time data integration. The updated platform now also supports z-score normalization of expression data, multi-gene pathway enrichment queries, and comparative gene-gene interaction networks for vitiligo and its comorbid autoimmune conditions. VIRdb v3.0 facilitates hypothesis generation, biomarker discovery, and therapeutic exploration, advancing vitiligo systems biology. The database is freely accessible at https://virdb.sbdaresearch.in/ .","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13646274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148302605","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

In silico models in oncology, neurology, and epidemiology: systems-level and multiscale perspectives. 肿瘤学、神经学和流行病学的计算机模型：系统级和多尺度视角。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-06-22 DOI: 10.1038/s41540-026-00769-1

Matteo Italia, José Garcia Otero, Juan Jiménez-Sánchez, Fabio Dercole, Juan Belmonte-Beitia

引用次数: 0

Resveratrol alleviates intervertebral disc degeneration by regulating ferroptosis of nucleus pulposus cells. 白藜芦醇通过调节髓核细胞的铁下垂减轻椎间盘退变。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-06-22 DOI: 10.1038/s41540-026-00761-9

Xiaoqiang Wang, Jiale Lv, Daqian Zhou, Weiye Cai, Chao Song, Zhijiang Fu, Zongchao Liu

{"title":"Resveratrol alleviates intervertebral disc degeneration by regulating ferroptosis of nucleus pulposus cells.","authors":"Xiaoqiang Wang, Jiale Lv, Daqian Zhou, Weiye Cai, Chao Song, Zhijiang Fu, Zongchao Liu","doi":"10.1038/s41540-026-00761-9","DOIUrl":"10.1038/s41540-026-00761-9","url":null,"abstract":"Intervertebral disc degeneration (IVDD) is a major contributor to chronic low back pain, yet its molecular mechanisms remain incompletely understood. Emerging evidence suggests that ferroptosis, an iron-dependent form of regulated cell death, may play a key role in the degeneration of nucleus pulposus cells (NPCs). However, its involvement in IVDD has not been systematically explored. Resveratrol (Res), a natural polyphenol with antioxidant and cytoprotective effects, shows therapeutic potential, but its regulatory role in ferroptosis during IVDD is unclear. In this study, bulk transcriptome analysis identified 22 ferroptosis-related differentially expressed genes, among which five hub genes (GPX4, FTH1, HMOX1, NCOA4, and TFRC) were strongly linked to ferroptosis and oxidative stress pathways. Single-cell transcriptome data further revealed dynamic expression of these genes in NP cells, showing decreased GPX4 and FTH1 and increased HMOX1, NCOA4, and TFRC along the differentiation trajectory. High-dimensional weighted gene co-expression network analysis (hdWGCNA) confirmed significant associations between ferroptosis-related gene modules and IVDD pathology. Validation using human clinical samples, NP cell models, and animal experiments demonstrated that Res alleviates IVDD by modulating hub gene expression and suppressing NP cell ferroptosis. Overall, this study highlights ferroptosis as a key mechanism driving IVDD and identifies resveratrol as a promising therapeutic candidate targeting NP cell ferroptosis.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148302483","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

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