NPJ Systems Biology and Applications最新文献_第5页

An in silico approach deciphering the commensal dynamics in the cutaneous milieu. 一种破译皮肤环境中共生动力学的计算机方法。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2025-05-07 DOI: 10.1038/s41540-025-00524-y

Sumathi Kalankariyan, Anjana Thottapillil, Abha Saxena, Manoj Srivatsn S, Vinitha Kadamkode, Renu Kapoor, Rupak Mitra, Janhavi Raut, K V Venkatesh

{"title":"An in silico approach deciphering the commensal dynamics in the cutaneous milieu.","authors":"Sumathi Kalankariyan, Anjana Thottapillil, Abha Saxena, Manoj Srivatsn S, Vinitha Kadamkode, Renu Kapoor, Rupak Mitra, Janhavi Raut, K V Venkatesh","doi":"10.1038/s41540-025-00524-y","DOIUrl":"https://doi.org/10.1038/s41540-025-00524-y","url":null,"abstract":"The skin microbiota, particularly coagulase-negative staphylococci (CoNS) such as S. epidermidis, plays a crucial role in maintaining skin health and immunity. S. epidermidis, a predominant commensal species, interacts intimately with keratinocytes to regulate immune responses and antimicrobial defence mechanisms. Metabolic byproducts like short-chain fatty acids (SCFAs) influence keratinocyte activation, while cell wall components engage Toll-like receptors (TLRs) to modulate inflammation. These interactions are fundamental for preserving skin homeostasis and combating pathogenic invaders. Our comprehensive mathematical model, integrating commensal dynamics, immune responses, and skin microenvironment variables, provides insights into these intricate interactions. The model delves into the complexities of skin scenarios and perturbations, aiming to understand the colonization dynamics of S. epidermidis and its influence on skin barrier functions. It examines how disruptions in key factors such as AMP, growth factor-mediated repair pathways, and filaggrin mutations influence the behaviour of the system. The study depicts the skin microenvironment as a highly dynamic one, highlighting the critical role of S. epidermidis and capturing its role in barrier dysfunction caused by internal and external factors. By offering insights into skin barrier function and immune responses, the model illuminates key interactions of commensals within the skin microenvironment which can ultimately benefit skin health.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"11 1","pages":"42"},"PeriodicalIF":3.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034185","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

Neural mechanisms balancing accuracy and flexibility in working memory and decision tasks. 平衡工作记忆和决策任务的准确性和灵活性的神经机制。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2025-05-07 DOI: 10.1038/s41540-025-00520-2

Han Yan, Jin Wang

{"title":"Neural mechanisms balancing accuracy and flexibility in working memory and decision tasks.","authors":"Han Yan, Jin Wang","doi":"10.1038/s41540-025-00520-2","DOIUrl":"https://doi.org/10.1038/s41540-025-00520-2","url":null,"abstract":"The living system follows the principles of physics, yet distinctive features, such as adaptability, differentiate it from conventional systems. The cognitive functions of decision-making (DM) and working memory (WM) are crucial for animal adaptation, but the underlying mechanisms are still unclear. To explore the mechanism underlying DM and WM functions, here we applied a general non-equilibrium landscape and flux approach to a biophysically based model that can perform decision-making and working memory functions. Our findings reveal that DM accuracy improved with stronger resting states in the circuit architecture with selective inhibition. However, the robustness of working memory against distractors was weakened. To address this, an additional non-selective input during the delay period of decision-making tasks was proposed as a mechanism to gate distractors with minimal increase in thermodynamic cost. This temporal gating mechanism, combined with the selective-inhibition circuit architecture, supports a dynamical modulation that emphasizes the robustness or flexibility to incoming stimuli in working memory tasks according to the cognitive task demands. Our approach offers a quantitative framework to uncover mechanisms underlying cognitive functions grounded in non-equilibrium physics.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"11 1","pages":"41"},"PeriodicalIF":3.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037551","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

Biochemical implementation of acceleration sensing and PIDA control. 生化实现加速度传感和PIDA控制。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2025-04-26 DOI: 10.1038/s41540-025-00514-0

Emmanouil Alexis, Sebastián Espinel-Ríos, Ioannis G Kevrekidis, José L Avalos

引用次数: 0

The Virtual Parkinsonian patient. 虚拟帕金森病人。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2025-04-26 DOI: 10.1038/s41540-025-00516-y

Marianna Angiolelli, Damien Depannemaecker, Hasnae Agouram, Jean Régis, Romain Carron, Marmaduke Woodman, Letizia Chiodo, Paul Triebkorn, Abolfazl Ziaeemehr, Meysam Hashemi, Alexandre Eusebio, Viktor Jirsa, Pierpaolo Sorrentino

{"title":"The Virtual Parkinsonian patient.","authors":"Marianna Angiolelli, Damien Depannemaecker, Hasnae Agouram, Jean Régis, Romain Carron, Marmaduke Woodman, Letizia Chiodo, Paul Triebkorn, Abolfazl Ziaeemehr, Meysam Hashemi, Alexandre Eusebio, Viktor Jirsa, Pierpaolo Sorrentino","doi":"10.1038/s41540-025-00516-y","DOIUrl":"https://doi.org/10.1038/s41540-025-00516-y","url":null,"abstract":"This study investigates the influence of the pharmacological nigrostriatal dopaminergic stimulation on the entire brain by analyzing EEG and deep electrodes, placed near the subthalamic nuclei, from 10 Parkinsonian patients before (OFF) and after (ON) L-Dopa administration. We characterize large-scale brain dynamics as the spatio-temporal spreading of aperiodic bursts. We then simulate the effects of L-Dopa utilizing a novel neural-mass model that includes the local dopamine concentration. Whole-brain dynamics are simulated for different dopaminergic tones, generating predictions for the expected dynamics, to be compared with empirical EEG and deep electrode data. To this end, we invert the model and infer the most likely dopaminergic tone from empirical data, correctly identifying a higher Dopaminergic tone in the ON-state, and a lower dopaminergic tone in the OFF-state, for each patient. In conclusion, we successfully infer the dopaminergic tone by integrating anatomical and functional knowledge into physiological predictions, using solid ground truth to validate our findings.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"11 1","pages":"40"},"PeriodicalIF":3.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029743","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

Exploring the role of EMT in ovarian cancer progression using a multiscale mathematical model. 利用多尺度数学模型探讨EMT在卵巢癌进展中的作用。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2025-04-17 DOI: 10.1038/s41540-025-00508-y

Samuel Oliver, Michael Williams, Mohit Kumar Jolly, Deyarina Gonzalez, Gibin Powathil

{"title":"Exploring the role of EMT in ovarian cancer progression using a multiscale mathematical model.","authors":"Samuel Oliver, Michael Williams, Mohit Kumar Jolly, Deyarina Gonzalez, Gibin Powathil","doi":"10.1038/s41540-025-00508-y","DOIUrl":"https://doi.org/10.1038/s41540-025-00508-y","url":null,"abstract":"Epithelial-to-mesenchymal transition (EMT) plays a key role in the progression of cancer tumours, significantly reducing the success of treatment. EMT occurs when a cell undergoes phenotypical changes, resulting in enhanced drug resistance, higher cell plasticity, and increased metastatic abilities. Here, we employ a 3D agent-based multiscale modelling framework using PhysiCell to explore the role of EMT over time in two cell lines, OVCAR-3 and SKOV-3. This approach allows us to investigate the spatiotemporal progression of ovarian cancer and the impacts of the conditions in the microenvironment. OVCAR-3 and SKOV-3 cell lines possess highly contrasting tumour layouts, allowing a wide range of different tumour dynamics and morphologies to be tested and studied. Along with performing sensitivity analysis on the model, simulation results capture the biological observations and trends seen in tumour growth and development, thus helping to obtain further insights into OVCAR-3 and SKOV-3 cell line dynamics.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"11 1","pages":"36"},"PeriodicalIF":3.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023723","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

MIRO1 mutation leads to metabolic maladaptation resulting in Parkinson's disease-associated dopaminergic neuron loss. MIRO1突变导致代谢失调，导致帕金森病相关多巴胺能神经元丢失。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2025-04-17 DOI: 10.1038/s41540-025-00509-x

Alise Zagare, Thomas Sauter, Kyriaki Barmpa, Maria Pacheco, Rejko Krüger, Jens Christian Schwamborn, Claudia Saraiva

{"title":"MIRO1 mutation leads to metabolic maladaptation resulting in Parkinson's disease-associated dopaminergic neuron loss.","authors":"Alise Zagare, Thomas Sauter, Kyriaki Barmpa, Maria Pacheco, Rejko Krüger, Jens Christian Schwamborn, Claudia Saraiva","doi":"10.1038/s41540-025-00509-x","DOIUrl":"https://doi.org/10.1038/s41540-025-00509-x","url":null,"abstract":"MIRO1 is a mitochondrial outer membrane protein important for mitochondrial distribution, dynamics and bioenergetics. Over the last decade, evidence has pointed to a link between MIRO1 and Parkinson's disease (PD) pathogenesis. Moreover, a heterozygous MIRO1 mutation (p.R272Q) was identified in a PD patient, from which an iPSC-derived midbrain organoid model was derived, showing MIRO1 mutant-dependent selective loss of dopaminergic neurons. Herein, we use patient-specific iPSC-derived midbrain organoids carrying the MIRO1 p.R272Q mutation to further explore the cellular and molecular mechanisms involved in dopaminergic neuron degeneration. Using single-cell RNA sequencing (scRNAseq) analysis and metabolic modeling we show that the MIRO1 p.R272Q mutation affects the dopaminergic neuron developmental path leading to metabolic deficits and disrupted neuron-astrocyte metabolic crosstalk, which might represent an important pathogenic mechanism leading to their loss.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"11 1","pages":"37"},"PeriodicalIF":3.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011846","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

Single cell RNAseq to identify subpopulations of glial progenitors in iPSC-derived oligodendroglial lineage cultures. 单细胞RNAseq在ipsc衍生的少突胶质谱系培养中鉴定胶质祖细胞亚群。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2025-04-15 DOI: 10.1038/s41540-025-00515-z

Gabriela J Blaszczyk, Valerio E C Piscopo, Taylor M Goldsmith, Alexandra Chapleau, Julien Sirois, Geneviève Bernard, Jack P Antel, Thomas M Durcan

引用次数: 0

Predicting gene expression changes from chromatin structure modification. 从染色质结构修饰预测基因表达变化。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2025-04-15 DOI: 10.1038/s41540-025-00510-4

Swayamshree Senapati, Inayat Ullah Irshad, Ajeet K Sharma, Hemant Kumar

{"title":"Predicting gene expression changes from chromatin structure modification.","authors":"Swayamshree Senapati, Inayat Ullah Irshad, Ajeet K Sharma, Hemant Kumar","doi":"10.1038/s41540-025-00510-4","DOIUrl":"https://doi.org/10.1038/s41540-025-00510-4","url":null,"abstract":"Spatial organization of chromatin plays a critical role in gene transcription, but connecting population-averaged HiC data to functional outcomes remains a challenge. We present a computational framework linking HiC contact map to gene transcription. Utilizing a bead-spring polymer model informed by HiC contact maps, we generate an ensemble of 3D conformations for a given genomic locus. These conformations are then coupled to gene transcription levels through a Markov chain model, with transition rates derived from molecular dynamics simulations. The efficacy of this framework is demonstrated by simulating the perturbation of a CTCF-mediated TAD boundary, impacting the expression of sox9 and kcnj2. Our model quantitatively reproduces experimentally observed changes in gene expression, revealing that the increased kcnj2 transcription is a consequence of enhancers within the sox9 TAD becoming accessible upon boundary disruption. Quantifying enhancer impact, our model can also identify functional enhancers. This framework enhances our understanding of the relationship between chromosome spatial architecture and gene regulation.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"11 1","pages":"34"},"PeriodicalIF":3.5,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12000410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029977","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

Quantitative cancer-immunity cycle modeling for predicting disease progression in advanced metastatic colorectal cancer. 定量癌症免疫周期模型预测晚期转移性结直肠癌的疾病进展。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2025-04-13 DOI: 10.1038/s41540-025-00513-1

Chenghang Li, Yongchang Wei, Jinzhi Lei

{"title":"Quantitative cancer-immunity cycle modeling for predicting disease progression in advanced metastatic colorectal cancer.","authors":"Chenghang Li, Yongchang Wei, Jinzhi Lei","doi":"10.1038/s41540-025-00513-1","DOIUrl":"https://doi.org/10.1038/s41540-025-00513-1","url":null,"abstract":"Patients with advanced metastatic colorectal cancer (mCRC) typically exhibit significant interindividual differences in treatment responses and face poor survival outcomes. To systematically analyze the heterogeneous tumor progression and recurrence observed in advanced mCRC patients, we developed a quantitative cancer-immunity cycle (QCIC) model. The QCIC model employs differential equations to capture the biological mechanisms underlying the cancer-immunity cycle and predicts tumor evolution dynamics under various treatment strategies through stochastic computational methods. We introduce the treatment response index (TRI) to quantify disease progression in virtual clinical trials and the death probability function (DPF) to estimate overall survival. Additionally, we investigate the impact of predictive biomarkers on survival prognosis in advanced mCRC patients, identifying tumor-infiltrating CD8+ cytotoxic T lymphocytes (CTLs) as key predictors of disease progression and the tumor-infiltrating CD4+ Th1/Treg ratio as a significant determinant of survival outcomes. This study presents an approach that bridges the gap between diverse clinical data sources and the generation of virtual patient cohorts, providing valuable insights into interindividual treatment variability and survival forecasting in mCRC patients.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"11 1","pages":"33"},"PeriodicalIF":3.5,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020721","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 mechanism for the emergence of low-dimensional structures in brain dynamics. 脑动力学中低维结构出现的机制。

IF 3.5 2区生物学

NPJ Systems Biology and Applications Pub Date : 2025-04-10 DOI: 10.1038/s41540-025-00499-w

Claudio Runfola, Spase Petkoski, Hiba Sheheitli, Christophe Bernard, Anthony R McIntosh, Viktor Jirsa

{"title":"A mechanism for the emergence of low-dimensional structures in brain dynamics.","authors":"Claudio Runfola, Spase Petkoski, Hiba Sheheitli, Christophe Bernard, Anthony R McIntosh, Viktor Jirsa","doi":"10.1038/s41540-025-00499-w","DOIUrl":"https://doi.org/10.1038/s41540-025-00499-w","url":null,"abstract":"Recent neuroimaging advancements have led to datasets characterized by an overwhelming number of features. Different dimensionality reduction techniques have been employed to uncover low-dimensional manifold representations underlying cognitive functions, while maintaining the fundamental characteristics of the data. These range from linear algorithms to more intricate non-linear methods for manifold extraction. However, the mechanisms responsible for the emergence of these simplified architectures remain a topic of debate. Motivated by concepts from dynamical systems theory, such as averaging and time-scale separation, our study introduces a novel mechanism for the collapse of high dimension brain dynamics onto lower dimensional manifolds. In our framework, fast neuronal activity oscillations average out over time, leading to the resulting dynamics approximating task-related processes occurring at slower time scales. This leads to the emergence of low-dimensional solutions as complex dynamics collapse into slow invariant manifolds. We test this assumption via neural simulations using a simplified model and then enhance the complexity of our simulations by incorporating a large-scale brain network model to mimic realistic neuroimaging signals. We observe in the different cases the convergence of fast oscillatory fluctuations of neuronal activity across time scales that correspond to simulated behavioral configurations. Specifically, by employing various dimensionality reduction techniques and manifold extraction schemes, we observe the reduction of high-dimensional dynamics onto lower-dimensional spaces, revealing emergent low-dimensional solutions. Our findings shed light on the role of frequency and time-scale separation in neuronal activity, proposing and testing a novel theoretical framework for understanding the inner mechanisms governing low-dimensional pattern formation in brain dynamics.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"11 1","pages":"32"},"PeriodicalIF":3.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036807","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