NPJ Systems Biology and Applications最新文献_第8页

Learning patient-specific spatial biomarker dynamics via operator learning for Alzheimer's disease progression. 通过算子学习了解阿尔茨海默病进展的患者特异性空间生物标志物动态。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-05-04 DOI: 10.1038/s41540-026-00719-x

Jindong Wang, Yutong Mao, Xiao Liu, Wenrui Hao

{"title":"Learning patient-specific spatial biomarker dynamics via operator learning for Alzheimer's disease progression.","authors":"Jindong Wang, Yutong Mao, Xiao Liu, Wenrui Hao","doi":"10.1038/s41540-026-00719-x","DOIUrl":"10.1038/s41540-026-00719-x","url":null,"abstract":"Alzheimer's disease (AD) is a complex, multifactorial neurodegenerative disorder with substantial heterogeneity in progression and treatment response. Despite recent therapeutic advances, predictive models capable of accurately forecasting individualized future biomarker states remain limited. Here, we present a machine learning-based operator learning framework for personalized modeling of AD progression, integrating longitudinal multimodal imaging, biomarker, and clinical data. Unlike conventional models with prespecified dynamics, our approach directly learns patient-specific disease operators governing the spatiotemporal evolution of amyloid, tau, and neurodegeneration biomarkers. Using Laplacian eigenfunction bases, we construct geometry-aware neural operators capable of capturing complex brain dynamics. Embedded within a digital twin paradigm, the framework enables individualized predictions, simulation of therapeutic interventions, and in silico clinical trials. Applied to AD clinical data, our method achieves high prediction accuracy exceeding 90% across multiple biomarkers, substantially outperforming existing approaches. This work offers a scalable, interpretable platform for precision modeling and personalized therapeutic optimization in neurodegenerative diseases.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13346838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841014","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

Design principles for robust multistability in coupled feedforward-feedback regulatory circuits. 耦合前馈-反馈调节电路鲁棒多稳定性设计原则。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-05-02 DOI: 10.1038/s41540-026-00731-1

Hong Qi, Zhi-Yu Zhao, Yu-Song Yin, Xiang Li, Chen Jia, Lei Zhang

{"title":"Design principles for robust multistability in coupled feedforward-feedback regulatory circuits.","authors":"Hong Qi, Zhi-Yu Zhao, Yu-Song Yin, Xiang Li, Chen Jia, Lei Zhang","doi":"10.1038/s41540-026-00731-1","DOIUrl":"10.1038/s41540-026-00731-1","url":null,"abstract":"Feedforward loops (FFLs) and feedback loops (FBLs) are ubiquitous network motifs that mediate signal filtering, pulse generation, and state switching; yet, how coupling FBLs to FFLs produces robust multistability-a key mechanism for cellular decision-making-remains unclear. Here, we systematically investigate coupled FFL-FBL architectures by focusing on two prevalent FFL types, each with AND or OR logic, yielding four distinct frameworks. For each framework, we enumerate all 36 = 729 possible circuits, corresponding to three possible states (activation, inhibition, or absence) for each of six feedback edges, formulate each circuit as a system of ordinary differential equations, and quantify robustness as the proportion of 100,000 randomly sampled parameter sets exhibiting multistability. Our results reveal two key principles. First, positive self-activation is a primary driver of multistability, but the identity of the critical node(s) depends on the FFL type and logic. Second, coherent FFLs support multistability more readily than incoherent ones, whereas the choice between AND and OR logic has a comparatively weaker effect. Notably, we identify representative high-performing circuits within each framework and find that a small set of circuit designs remain robustly multistable across all four frameworks. These findings advance the theoretical understanding of motif design and provide practical guidelines for engineering synthetic multistable circuits.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13341765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818467","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

Sometimes extracellular recordings fail for good reasons. 有时细胞外记录失败是有原因的。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-05-02 DOI: 10.1038/s41540-026-00730-2

Karoline Horgmo Jæger, Aslak Tveito

{"title":"Sometimes extracellular recordings fail for good reasons.","authors":"Karoline Horgmo Jæger, Aslak Tveito","doi":"10.1038/s41540-026-00730-2","DOIUrl":"10.1038/s41540-026-00730-2","url":null,"abstract":"Excitable cells are commonly studied via the extracellular potentials (EPs) they generate, which underlie signals in electroencephalography (EEG), electrocardiography (ECG), and multielectrode array (MEA) recordings. However, some excitable systems produce little or no detectable EPs, for reasons that remain poorly understood. Here we show mathematically that homogeneous excitable cells and tissues - with spatially uniform ion channel distributions and no external stimulation - are extracellularly silent during spatially uniform, non-propagating action potentials (i.e., in the absence of a traveling wavefront). Specifically, an isolated, autonomous cell with uniform membrane properties generates zero EP, independent of shape, kinetics, or model complexity. The result extends to coupled cells provided the tissue remains fully homogeneous. EPs emerge only from spatial inhomogeneities, propagating electrical waves, or applied currents. We demonstrate the physiological relevance of this principle in Purkinje neurons, where clustering of sodium channels enables ephaptic synchronization, while uniform cells remain asynchronous and undetectable extracellularly. We further show that connected human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and pancreatic β-cells exhibit EPs in proportion to cellular or tissue-level heterogeneity.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13342592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818490","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

Association-sensory spatiotemporal hierarchy and functional gradient-regularised recurrent neural network with implications for schizophrenia. 联想-感觉时空层次和功能梯度-正则化递归神经网络对精神分裂症的影响。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-04-30 DOI: 10.1038/s41540-026-00727-x

Subati Abulikemu, Puria Radmard, Michail Mamalakis, John Suckling

{"title":"Association-sensory spatiotemporal hierarchy and functional gradient-regularised recurrent neural network with implications for schizophrenia.","authors":"Subati Abulikemu, Puria Radmard, Michail Mamalakis, John Suckling","doi":"10.1038/s41540-026-00727-x","DOIUrl":"10.1038/s41540-026-00727-x","url":null,"abstract":"The human neocortex is functionally organised at its highest level along a continuous sensory-to-association (AS) hierarchy. This study investigates two questions-how this hierarchy is structurally altered in schizophrenia, and what these alterations imply for neural dynamics and cognitive computation. Using a large fMRI dataset (N = 355), we extracted individual AS gradients via spectral analysis of brain connectivity and quantified hierarchical organisation by the gradient range. Schizophrenia showed a compressed AS hierarchy, indicating reduced functional differentiation. Estimating neural timescale (autocorrelation decay constant) with the Ornstein-Uhlenbeck process, we observed that the most specialised, locally cohesive regions at the gradient extremes exhibit longer timescales, an empirical spatiotemporal mapping that is attenuated in schizophrenia. To probe the computational consequences of this compression, we used the gradients to regularise subject-specific recurrent neural networks (RNNs) trained on working memory tasks. Networks endowed with greater gradient range learned more efficiently, plateaued at lower task loss, and maintained stronger alignment to the prescribed AS hierarchical geometry. Fixed-point linearisation showed that high-range networks settled into more stable neural states during memory delay, evidenced by lower energy and smaller maximal Jacobian eigenvalues. This gradient-regularised RNN framework thereby links large-scale cortical architecture with fixed point stability, providing a computational hypothesis that AS gradient de-differentiation can destabilise neural computations in schizophrenia, convergently supported by empirical timescale flattening along AS gradient and model-based evidence of less stable fixed points.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13338132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777154","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 AI, mechanistic modelling and network approaches in systems biology for translational research. 整合人工智能，机制建模和网络方法在系统生物学转化研究。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-04-29 DOI: 10.1038/s41540-026-00726-y

Xin Lai, Jing Tang

引用次数: 0

Rewiring miR-22/SNAI1 via CRISPR-based edge editing destabilizes the epithelial phenotype. 通过基于crispr的边缘编辑重新连接miR-22/SNAI1会破坏上皮表型的稳定性。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-04-29 DOI: 10.1038/s41540-026-00720-4

John T Nguyen, Lijia Huang, Herbert Levine, Mingyang Lu, Leonidas Bleris

{"title":"Rewiring miR-22/SNAI1 via CRISPR-based edge editing destabilizes the epithelial phenotype.","authors":"John T Nguyen, Lijia Huang, Herbert Levine, Mingyang Lu, Leonidas Bleris","doi":"10.1038/s41540-026-00720-4","DOIUrl":"10.1038/s41540-026-00720-4","url":null,"abstract":"Epithelial-to-Mesenchymal Transition (EMT) is a critical biological process by which cells acquire enhanced migratory and invasive properties. A key signaling pathway involved in EMT phenotypes includes transforming growth factor β (TGFβ) and transcription factors (TFs) such as SNAIL, ZEB, and TWIST. Additionally, microRNAs (miRNAs) - small, non-coding molecules that regulate gene expression by targeting mRNA transcripts - directly regulate genes central to the EMT process. Notably, miR-22 has been identified as a significant regulator of EMT through direct inhibition of EMT drivers like SNAI1 and indirect regulation of upstream genes. In this study, we performed CRISPR-based network rewiring by selectively removing an edge-the connection between two nodes-to investigate its impact on EMT dynamics. Specifically, we disrupted the connection between miR-22 and SNAI1 without affecting other interactions involving miR-22 or SNAI1 and examined the resulting effects on EMT. We demonstrate that the removal of the miR-22 target site from the SNAI1 gene renders cells more sensitive to TGFβ-mediated EMT. This finding highlights the unique advantage of edge-specific perturbation by ablating the direct regulatory connection between miR-22 and SNAI1. We demonstrate that all measured downstream effects on EMT can be attributed to this single interaction, independent of miR-22's influence on other targets or indirect pathways. More generally, our results underscore the importance of CRISPR-mediated edge ablation for exploring the interactions that govern biological networks and highlight an underexplored opportunity to develop edge-based therapeutic modalities.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13333950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777284","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-trajectory Bayesian modeling reveals multi-state diffusion of the MSH sliding clamp. 单轨迹贝叶斯模型揭示了MSH滑动钳的多状态扩散。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-04-29 DOI: 10.1038/s41540-026-00715-1

Seongyu Park, Inho Yang, Jinseob Lee, Sinwoo Kim, Juana Martín-López, Richard Fishel, Jong-Bong Lee, Jae-Hyung Jeon

{"title":"Single-trajectory Bayesian modeling reveals multi-state diffusion of the MSH sliding clamp.","authors":"Seongyu Park, Inho Yang, Jinseob Lee, Sinwoo Kim, Juana Martín-López, Richard Fishel, Jong-Bong Lee, Jae-Hyung Jeon","doi":"10.1038/s41540-026-00715-1","DOIUrl":"10.1038/s41540-026-00715-1","url":null,"abstract":"DNA mismatch repair (MMR) is an essential mechanism for preserving genomic integrity across diverse living organisms. In this process, MutS homologs (MSH) play crucial roles in detecting mismatched basepairs and recruiting downstream MMR proteins. MSH exhibits distinct functions and diffusion dynamics before and after mismatch recognition. The ADP-bound MSH, known as the searching clamp, scans DNA via rotational diffusion along the backbone, while ATP binding produces a stable sliding clamp. Recent experiments have challenged the conventional view that the ATP-bound clamp performs a simple Brownian motion. Here, we investigate the diffusion dynamics of the ATP-bound MSH sliding clamp using single-particle tracking and a Bayesian diffusion-state analysis framework. Our quantitative modeling reveals that the diffusion characteristics defy explanation by a single-state diffusion mechanism. Instead, we identify three discrete diffusion states with distinct coefficients (D1 = 1.86 × 10-2 μm2/s, D2 = 1.30 × 10-1 μm2/s, and D3 = 9.64 × 10-1 μm2/s) and cross-state transitions predominantly mediated via the intermediate D2-state. We propose that these multi-state dynamics reflect conformational switching in the MSH clamp, highlighting a more intricate and regulated diffusion mechanism than previously recognized.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13334046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777352","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

From genes to germ layers: virtual twins of gastruloids. 从基因到胚层：几乎是类胃原体的双胞胎。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-04-28 DOI: 10.1038/s41540-026-00709-z

Leona M Irwin, Shaun M Cowley, Himanshu Kaul

引用次数: 0

Biomarker identification of triple negative breast cancer subtypes using machine learning. 使用机器学习识别三阴性乳腺癌亚型的生物标志物。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-04-27 DOI: 10.1038/s41540-026-00721-3

Syed Mohammad, Vaisali Chandrasekar, Ajay Vikram Singh, Omar M Aboumarzouk, Artefaa Al-Shamari, Sunil Choudhary, Neha Gupta, Sarada Prasad Dakua

{"title":"Biomarker identification of triple negative breast cancer subtypes using machine learning.","authors":"Syed Mohammad, Vaisali Chandrasekar, Ajay Vikram Singh, Omar M Aboumarzouk, Artefaa Al-Shamari, Sunil Choudhary, Neha Gupta, Sarada Prasad Dakua","doi":"10.1038/s41540-026-00721-3","DOIUrl":"10.1038/s41540-026-00721-3","url":null,"abstract":"Triple Negative Breast Cancer is a clinically aggressive and molecularly heterogeneous subtype of breast cancer that currently lacks effective targeted therapies. Recognising biologically distinct subtypes within this disease is crucial for enhancing diagnosis, prognosis, and therapeutic approaches. This study introduces a comprehensive analytical framework that integrates unsupervised clustering, differential gene expression analysis, pathway enrichment, and explainable machine learning to delineate robust molecular subtypes of Triple Negative Breast Cancer and their corresponding biological mechanisms. Consensus clustering is used to divide patients into different subgroups by analyzing publicly available gene expression datasets. Pathway enrichment analysis is used to find subtype-specific gene signatures and figure out what they do. To improve interpretability and translational relevance, a model-agnostic explainable artificial intelligence approach is used to measure how much key genes and pathways help with subtype classification. The prognostic significance of the genes is further studied to demonstrate the clinical applicability of the identified biomarkers. The suggested framework works well with many different machine learning models and makes it possible to find biologically meaningful biomarkers linked to therapeutic resistance and the ability to spread cancer. These findings elucidate the molecular heterogeneity of Triple Negative Breast Cancer and endorse the advancement of more accurate and interpretable biomarker-driven clinical strategies.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777207","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

Liver progenitor cells perform wound healing in a scratch assay by concerted bistable circuits. 肝祖细胞执行伤口愈合在划痕试验协调双稳态电路。

IF 4.4 2区生物学

NPJ Systems Biology and Applications Pub Date : 2026-04-25 DOI: 10.1038/s41540-026-00724-0

Marija Lazovska, Kristine Salmina, Dace Pjanova, Pawel Zayakin, Bogdan I Gerashchenko, Jekaterina Erenpreisa

{"title":"Liver progenitor cells perform wound healing in a scratch assay by concerted bistable circuits.","authors":"Marija Lazovska, Kristine Salmina, Dace Pjanova, Pawel Zayakin, Bogdan I Gerashchenko, Jekaterina Erenpreisa","doi":"10.1038/s41540-026-00724-0","DOIUrl":"10.1038/s41540-026-00724-0","url":null,"abstract":"Liver progenitor cells (LPC) exhibit the potential to differentiate into both hepatocytes and cholangiocytes, making them promising candidates for cell therapy in cases of severe liver pathology. However, the mechanisms of LPCs regeneration are unclear. Here, we utilised rat liver stem-like epithelial cells (WB-F344) in a wound-healing assay. The scratched near-confluent monolayer (70% area removed) underwent G1-arrest, transient bi-nucleation at 10-12 h post-injury, the epithelial-mesenchymal transition, and motion of cell fraction into the wounded areas. The transient displacement of the nuclear NANOG with upregulated p16Ink4a, loss of epithelial albumin and CK7 markers, along with transient YAP1/Hippo and TWIST 1 activation, was seen near the wound edge. At 24 h, G1-arrest was overcome, followed by a proliferation boost. At 40-48 h, proliferation was accomplished by reconstitution of epithelial tissue, NANOG was restored in the cell nucleus, and p16Ink4a left it. Thus, wound healing was performed by concerted, molecular and cellular, bistable circuits.","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13319447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777317","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