NPJ Systems Biology and Applications最新文献

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A multiscale model of immune surveillance in micrometastases gives insights on cancer patient digital twins. 微转移免疫监测的多尺度模型为癌症患者数字双胞胎提供了见解。
IF 3.5 2区 生物学
NPJ Systems Biology and Applications Pub Date : 2024-12-04 DOI: 10.1038/s41540-024-00472-z
Heber L Rocha, Boris Aguilar, Michael Getz, Ilya Shmulevich, Paul Macklin
{"title":"A multiscale model of immune surveillance in micrometastases gives insights on cancer patient digital twins.","authors":"Heber L Rocha, Boris Aguilar, Michael Getz, Ilya Shmulevich, Paul Macklin","doi":"10.1038/s41540-024-00472-z","DOIUrl":"10.1038/s41540-024-00472-z","url":null,"abstract":"<p><p>Metastasis is the leading cause of death in patients with cancer, driving considerable scientific and clinical interest in immunosurveillance of micrometastases. We investigated this process by creating a multiscale mathematical model to study the interactions between the immune system and the progression of micrometastases in general epithelial tissue. We analyzed the parameter space of the model using high-throughput computing resources to generate over 100,000 virtual patient trajectories. We demonstrated that the model could recapitulate a wide variety of virtual patient trajectories, including uncontrolled growth, partial response, and complete immune response to tumor growth. We classified the virtual patients and identified key patient parameters with the greatest effect on the simulated immunosurveillance. We highlight the lessons derived from this analysis and their impact on the nascent field of cancer patient digital twins (CPDTs). While CPDTs could enable clinicians to systematically dissect the complexity of cancer in each individual patient and inform treatment choices, our work shows that key challenges remain before we can reach this vision. In particular, we show that there remain considerable uncertainties in immune responses, unreliable patient stratification, and unpredictable personalized treatment. Nonetheless, we also show that in spite of these challenges, patient-specific models suggest strategies to increase control of clinically undetectable micrometastases even without complete parameter certainty.</p>","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"10 1","pages":"144"},"PeriodicalIF":3.5,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770735","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 cell graph analysis reveals skin tissue organization characteristic for cutaneous T cell lymphoma. 空间细胞图分析揭示皮肤T细胞淋巴瘤的皮肤组织特征。
IF 3.5 2区 生物学
NPJ Systems Biology and Applications Pub Date : 2024-12-02 DOI: 10.1038/s41540-024-00474-x
Suryadipto Sarkar, Anna Möller, Anne Hartebrodt, Michael Erdmann, Christian Ostalecki, Andreas Baur, David B Blumenthal
{"title":"Spatial cell graph analysis reveals skin tissue organization characteristic for cutaneous T cell lymphoma.","authors":"Suryadipto Sarkar, Anna Möller, Anne Hartebrodt, Michael Erdmann, Christian Ostalecki, Andreas Baur, David B Blumenthal","doi":"10.1038/s41540-024-00474-x","DOIUrl":"10.1038/s41540-024-00474-x","url":null,"abstract":"<p><p>Cutaneous T-cell lymphomas (CTCLs) are non-Hodgkin lymphomas caused by malignant T cells which migrate to the skin and lead to rash-like lesions which can be difficult to distinguish from inflammatory skin conditions like atopic dermatitis (AD) and psoriasis (PSO). To characterize CTCL in comparison to these differential diagnoses, we carried out multi-antigen imaging on 69 skin tissue samples (21 CTCL, 23 AD, 25 PSO). The resulting protein abundance maps were then analyzed via scoring functions to quantify the heterogeneity of the individual cells' neighborhoods within spatial graphs inferred from the cells' positions in the tissue samples. Our analyses reveal characteristic patterns of skin tissue organization in CTCL as compared to AD and PSO, including a combination of increased local entropy and egophily in T-cell neighborhoods. These results could not only pave the way for high-precision diagnosis of CTCL, but may also facilitate further insights into cellular disease mechanisms.</p>","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"10 1","pages":"143"},"PeriodicalIF":3.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770757","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
Microarray integrated spatial transcriptomics (MIST) for affordable and robust digital pathology. 微阵列集成空间转录组学(MIST)可负担得起和强大的数字病理学。
IF 3.5 2区 生物学
NPJ Systems Biology and Applications Pub Date : 2024-11-30 DOI: 10.1038/s41540-024-00462-1
Juwayria, Priyansh Shrivastava, Kaustar Yadav, Sourabh Das, Shubham Mittal, Sunil Kumar, Deepali Jain, Prabhat Singh Malik, Ishaan Gupta
{"title":"Microarray integrated spatial transcriptomics (MIST) for affordable and robust digital pathology.","authors":"Juwayria, Priyansh Shrivastava, Kaustar Yadav, Sourabh Das, Shubham Mittal, Sunil Kumar, Deepali Jain, Prabhat Singh Malik, Ishaan Gupta","doi":"10.1038/s41540-024-00462-1","DOIUrl":"https://doi.org/10.1038/s41540-024-00462-1","url":null,"abstract":"<p><p>10X Visium, a popular Spatial transcriptomics (ST) method, faces limited adoption due to its high cost and restricted sample usage per slide. To address these issues, we propose Microarray Integrated Spatial Transcriptomics (MIST), combining conventional tissue microarray (TMA) with Visium, using laser-cutting and 3D printing to enhance slide throughput. Our design facilitates independent replication and customization in individual labs to suit specific experimental needs. We provide a step-by-step guide from designing TMAs to the library preparation step. We demonstrate MIST's cost-effectiveness and technical benefits over Visium and GeoMx Nanostring. We also introduce 'AnnotateMap', a novel computational tool for efficient analysis of multiple ROIs processed through MIST.</p>","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"10 1","pages":"142"},"PeriodicalIF":3.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770753","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
Immune digital twins for complex human pathologies: applications, limitations, and challenges. 用于复杂人类病理的免疫数字双胞胎:应用、限制和挑战。
IF 3.5 2区 生物学
NPJ Systems Biology and Applications Pub Date : 2024-11-30 DOI: 10.1038/s41540-024-00450-5
Anna Niarakis, Reinhard Laubenbacher, Gary An, Yaron Ilan, Jasmin Fisher, Åsmund Flobak, Kristin Reiche, María Rodríguez Martínez, Liesbet Geris, Luiz Ladeira, Lorenzo Veschini, Michael L Blinov, Francesco Messina, Luis L Fonseca, Sandra Ferreira, Arnau Montagud, Vincent Noël, Malvina Marku, Eirini Tsirvouli, Marcella M Torres, Leonard A Harris, T J Sego, Chase Cockrell, Amanda E Shick, Hasan Balci, Albin Salazar, Kinza Rian, Ahmed Abdelmonem Hemedan, Marina Esteban-Medina, Bernard Staumont, Esteban Hernandez-Vargas, Shiny Martis B, Alejandro Madrid-Valiente, Panagiotis Karampelesis, Luis Sordo Vieira, Pradyumna Harlapur, Alexander Kulesza, Niloofar Nikaein, Winston Garira, Rahuman S Malik Sheriff, Juilee Thakar, Van Du T Tran, Jose Carbonell-Caballero, Soroush Safaei, Alfonso Valencia, Andrei Zinovyev, James A Glazier
{"title":"Immune digital twins for complex human pathologies: applications, limitations, and challenges.","authors":"Anna Niarakis, Reinhard Laubenbacher, Gary An, Yaron Ilan, Jasmin Fisher, Åsmund Flobak, Kristin Reiche, María Rodríguez Martínez, Liesbet Geris, Luiz Ladeira, Lorenzo Veschini, Michael L Blinov, Francesco Messina, Luis L Fonseca, Sandra Ferreira, Arnau Montagud, Vincent Noël, Malvina Marku, Eirini Tsirvouli, Marcella M Torres, Leonard A Harris, T J Sego, Chase Cockrell, Amanda E Shick, Hasan Balci, Albin Salazar, Kinza Rian, Ahmed Abdelmonem Hemedan, Marina Esteban-Medina, Bernard Staumont, Esteban Hernandez-Vargas, Shiny Martis B, Alejandro Madrid-Valiente, Panagiotis Karampelesis, Luis Sordo Vieira, Pradyumna Harlapur, Alexander Kulesza, Niloofar Nikaein, Winston Garira, Rahuman S Malik Sheriff, Juilee Thakar, Van Du T Tran, Jose Carbonell-Caballero, Soroush Safaei, Alfonso Valencia, Andrei Zinovyev, James A Glazier","doi":"10.1038/s41540-024-00450-5","DOIUrl":"10.1038/s41540-024-00450-5","url":null,"abstract":"<p><p>Digital twins represent a key technology for precision health. Medical digital twins consist of computational models that represent the health state of individual patients over time, enabling optimal therapeutics and forecasting patient prognosis. Many health conditions involve the immune system, so it is crucial to include its key features when designing medical digital twins. The immune response is complex and varies across diseases and patients, and its modelling requires the collective expertise of the clinical, immunology, and computational modelling communities. This review outlines the initial progress on immune digital twins and the various initiatives to facilitate communication between interdisciplinary communities. We also outline the crucial aspects of an immune digital twin design and the prerequisites for its implementation in the clinic. We propose some initial use cases that could serve as \"proof of concept\" regarding the utility of immune digital technology, focusing on diseases with a very different immune response across spatial and temporal scales (minutes, days, months, years). Lastly, we discuss the use of digital twins in drug discovery and point out emerging challenges that the scientific community needs to collectively overcome to make immune digital twins a reality.</p>","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"10 1","pages":"141"},"PeriodicalIF":3.5,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770739","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 mathematical framework for comparison of intermittent versus continuous adaptive chemotherapy dosing in cancer. 癌症间歇与连续适应性化疗剂量比较的数学框架。
IF 3.5 2区 生物学
NPJ Systems Biology and Applications Pub Date : 2024-11-29 DOI: 10.1038/s41540-024-00461-2
Cordelia McGehee, Yoichiro Mori
{"title":"A mathematical framework for comparison of intermittent versus continuous adaptive chemotherapy dosing in cancer.","authors":"Cordelia McGehee, Yoichiro Mori","doi":"10.1038/s41540-024-00461-2","DOIUrl":"10.1038/s41540-024-00461-2","url":null,"abstract":"<p><p>Chemotherapy resistance in cancer remains a barrier to curative therapy in advanced disease. Dosing of chemotherapy is often chosen based on the maximum tolerated dosing principle; drugs that are more toxic to normal tissue are typically given in on-off cycles, whereas those with little toxicity are dosed daily. When intratumoral cell-cell competition between sensitive and resistant cells drives chemotherapy resistance development, it has been proposed that adaptive chemotherapy dosing regimens, whereby a drug is given intermittently at a fixed-dose or continuously at a variable dose based on tumor size, may lengthen progression-free survival over traditional dosing. Indeed, in mathematical models using modified Lotka-Volterra systems to study dose timing, rapid competitive release of the resistant population and tumor outgrowth is apparent when cytotoxic chemotherapy is maximally dosed. This effect is ameliorated with continuous (dose modulation) or intermittent (dose skipping) adaptive therapy in mathematical models and experimentally, however, direct comparison between these two modalities has been limited. Here, we develop a mathematical framework to formally analyze intermittent adaptive therapy in the context of bang-bang control theory. We prove that continuous adaptive therapy is superior to intermittent adaptive therapy in its robustness to uncertainty in initial conditions, time to disease progression, and cumulative toxicity. We additionally show that under certain conditions, resistant population extinction is possible under adaptive therapy or fixed-dose continuous therapy. Here, continuous fixed-dose therapy is more robust to uncertainty in initial conditions than adaptive therapy, suggesting an advantage of traditional dosing paradigms.</p>","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"10 1","pages":"140"},"PeriodicalIF":3.5,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11607384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755219","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
Robust parameter estimation and identifiability analysis with hybrid neural ordinary differential equations in computational biology. 计算生物学中混合神经常微分方程鲁棒参数估计及可辨识性分析。
IF 3.5 2区 生物学
NPJ Systems Biology and Applications Pub Date : 2024-11-29 DOI: 10.1038/s41540-024-00460-3
Stefano Giampiccolo, Federico Reali, Anna Fochesato, Giovanni Iacca, Luca Marchetti
{"title":"Robust parameter estimation and identifiability analysis with hybrid neural ordinary differential equations in computational biology.","authors":"Stefano Giampiccolo, Federico Reali, Anna Fochesato, Giovanni Iacca, Luca Marchetti","doi":"10.1038/s41540-024-00460-3","DOIUrl":"10.1038/s41540-024-00460-3","url":null,"abstract":"<p><p>Parameter estimation is one of the central challenges in computational biology. In this paper, we present an approach to estimate model parameters and assess their identifiability in cases where only partial knowledge of the system structure is available. The partially known model is embedded into a system of hybrid neural ordinary differential equations, with neural networks capturing unknown system components. Integrating neural networks into the model presents two main challenges: global exploration of the mechanistic parameter space during optimization and potential loss of parameter identifiability due to the neural network flexibility. To tackle these challenges, we treat biological parameters as hyperparameters, allowing for global search during hyperparameter tuning. We then conduct a posteriori identifiability analysis, extending a well-established method for mechanistic models. The pipeline performance is evaluated on three test cases designed to replicate real-world conditions, including noisy data and limited system observability.</p>","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"10 1","pages":"139"},"PeriodicalIF":3.5,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751433","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 deep learning approach predicting the activity of COVID-19 therapeutics and vaccines against emerging variants. 预测 COVID-19 疗法和疫苗对新出现变体的活性的深度学习方法。
IF 3.5 2区 生物学
NPJ Systems Biology and Applications Pub Date : 2024-11-27 DOI: 10.1038/s41540-024-00471-0
Robert P Matson, Isin Y Comba, Eli Silvert, Michiel J M Niesen, Karthik Murugadoss, Dhruti Patwardhan, Rohit Suratekar, Elizabeth-Grace Goel, Brittany J Poelaert, Kanny K Wan, Kyle R Brimacombe, A J Venkatakrishnan, Venky Soundararajan
{"title":"A deep learning approach predicting the activity of COVID-19 therapeutics and vaccines against emerging variants.","authors":"Robert P Matson, Isin Y Comba, Eli Silvert, Michiel J M Niesen, Karthik Murugadoss, Dhruti Patwardhan, Rohit Suratekar, Elizabeth-Grace Goel, Brittany J Poelaert, Kanny K Wan, Kyle R Brimacombe, A J Venkatakrishnan, Venky Soundararajan","doi":"10.1038/s41540-024-00471-0","DOIUrl":"10.1038/s41540-024-00471-0","url":null,"abstract":"<p><p>Understanding which viral variants evade neutralization is crucial for improving antibody-based treatments, especially with rapidly evolving viruses like SARS-CoV-2. Yet, conventional assays are labor intensive and cannot capture the full spectrum of variants. We present a deep learning approach to predict changes in neutralizing antibody activity of COVID-19 therapeutics and vaccine-elicited sera/plasma against emerging viral variants. Our approach leverages data of 67,885 unique SARS-CoV-2 Spike sequences and 7,069 in vitro assays. The resulting model accurately predicted fold changes in neutralizing activity (R<sup>2</sup> = 0.77) for a test set (N = 980) of data collected up to eight months after the training data. Next, the model was used to predict changes in activity of current therapeutic and vaccine-induced antibodies against emerging SARS-CoV-2 lineages. Consistent with other work, we found significantly reduced activity against newer XBB descendants, notably EG.5, FL.1.5.1, and XBB.1.16; primarily attributed to the F456L spike mutation.</p>","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"10 1","pages":"138"},"PeriodicalIF":3.5,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740098","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
Network structure and fluctuation data improve inference of metabolic interaction strengths with the inverse Jacobian. 网络结构和波动数据提高了利用逆雅各布函数推断代谢相互作用强度的能力。
IF 3.5 2区 生物学
NPJ Systems Biology and Applications Pub Date : 2024-11-23 DOI: 10.1038/s41540-024-00457-y
Jiahang Li, Wolfram Weckwerth, Steffen Waldherr
{"title":"Network structure and fluctuation data improve inference of metabolic interaction strengths with the inverse Jacobian.","authors":"Jiahang Li, Wolfram Weckwerth, Steffen Waldherr","doi":"10.1038/s41540-024-00457-y","DOIUrl":"10.1038/s41540-024-00457-y","url":null,"abstract":"<p><p>Based on high-throughput metabolomics data, the recently introduced inverse differential Jacobian algorithm can infer regulatory factors and molecular causality within metabolic networks close to steady-state. However, these studies assumed perturbations acting independently on each metabolite, corresponding to metabolic system fluctuations. In contrast, emerging evidence puts forward internal network fluctuations, particularly from gene expression fluctuations, leading to correlated perturbations on metabolites. Here, we propose a novel approach that exploits these correlations to quantify relevant metabolic interactions. By integrating enzyme-related fluctuations in the construction of an appropriate fluctuation matrix, we are able to exploit the underlying reaction network structure for the inverse Jacobian algorithm. We applied this approach to a model-based artificial dataset for validation, and to an experimental breast cancer dataset with two different cell lines. By highlighting metabolic interactions with significantly changed interaction strengths, the inverse Jacobian approach identified critical dynamic regulation points which are confirming previous breast cancer studies.</p>","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"10 1","pages":"137"},"PeriodicalIF":3.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695603","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
Enhancing localized chemotherapy with anti-angiogenesis and nanomedicine synergy for improved tumor penetration in well-vascularized tumors. 利用抗血管生成和纳米药物的协同作用加强局部化疗,改善血管发达肿瘤的穿透性。
IF 3.5 2区 生物学
NPJ Systems Biology and Applications Pub Date : 2024-11-20 DOI: 10.1038/s41540-024-00467-w
Mohammad Souri, Sohail Elahi, Farshad Moradi Kashkooli, Mohammad Kohandel, M Soltani
{"title":"Enhancing localized chemotherapy with anti-angiogenesis and nanomedicine synergy for improved tumor penetration in well-vascularized tumors.","authors":"Mohammad Souri, Sohail Elahi, Farshad Moradi Kashkooli, Mohammad Kohandel, M Soltani","doi":"10.1038/s41540-024-00467-w","DOIUrl":"10.1038/s41540-024-00467-w","url":null,"abstract":"<p><p>Intratumoral delivery and localized chemotherapy have demonstrated promise in tumor treatment; however, the rapid drainage of therapeutic agents from well-vascularized tumors limits their ability to achieve maximum therapeutic efficacy. Therefore, innovative approaches are needed to enhance treatment efficacy in such tumors. This study utilizes a mathematical modeling platform to assess the efficacy of combination therapy using anti-angiogenic drugs and drug-loaded nanoparticles. Anti-angiogenic drugs are included to reduce blood microvascular density and facilitate drug retention in the extracellular space. In addition, incorporating negatively charged nanoparticles aims to enhance diffusion and distribution of therapeutic agents within well-vascularized tumors. The findings indicate that, in the case of direct injection of free drugs, using compounds with lower drainage rates and higher diffusion coefficients is beneficial for achieving broader diffusion. Otherwise, drugs tend to accumulate primarily around the injection site. For instance, the drug doxorubicin, known for its rapid drainage, requires the prior direct injection of an anti-angiogenic drug with a high diffusion rate to reduce microvascular density and facilitate broader distribution, enhancing penetration depth by 200%. Moreover, the results demonstrate that negatively charged nanoparticles effectively disperse throughout the tissue due to their high diffusion coefficient. In addition, a faster drug release rate from nanoparticles further enhance treatment efficacy, achieving the necessary concentration for complete eradication of tumor compared to slower drug release rates. This study demonstrates the potential of utilizing negatively charged nanoparticles loaded with chemotherapy drugs exhibiting high release rates for localized chemotherapy through intratumoral injection in well-vascularized tumors.</p>","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"10 1","pages":"136"},"PeriodicalIF":3.5,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11579323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682440","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
General relationship of local topologies, global dynamics, and bifurcation in cellular networks. 蜂窝网络中局部拓扑、全局动态和分岔的一般关系。
IF 3.5 2区 生物学
NPJ Systems Biology and Applications Pub Date : 2024-11-18 DOI: 10.1038/s41540-024-00470-1
Qing Hu, Ruoyu Tang, Xinyu He, Ruiqi Wang
{"title":"General relationship of local topologies, global dynamics, and bifurcation in cellular networks.","authors":"Qing Hu, Ruoyu Tang, Xinyu He, Ruiqi Wang","doi":"10.1038/s41540-024-00470-1","DOIUrl":"10.1038/s41540-024-00470-1","url":null,"abstract":"<p><p>Cellular networks realize their functions by integrating intricate information embedded within local structures such as regulatory paths and feedback loops. However, the precise mechanisms of how local topologies determine global network dynamics and induce bifurcations remain unidentified. A critical step in unraveling the integration is to identify the governing principles, which underlie the mechanisms of information flow. Here, we develop the cumulative linearized approximation (CLA) algorithm to address this issue. Based on perturbation analysis and network decomposition, we theoretically demonstrate how perturbations affect the equilibrium variations through the integration of all regulatory paths and how stability of the equilibria is determined by distinct feedback loops. Two illustrative examples, i.e., a three-variable bistable system and a more intricate epithelial-mesenchymal transition (EMT) network, are chosen to validate the feasibility of this approach. These results establish a solid foundation for understanding information flow across cellular networks, highlighting the critical roles of local topologies in determining global network dynamics and the emergence of bifurcations within these networks. This work introduces a novel framework for investigating the general relationship between local topologies and global dynamics of cellular networks under perturbations.</p>","PeriodicalId":19345,"journal":{"name":"NPJ Systems Biology and Applications","volume":"10 1","pages":"135"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667838","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
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