Agent-Based Modeling to Reveal Mechanisms of Idiopathic Interstitial Lung Disease

基于代理的建模揭示特发性间质性肺疾病的机制

基本信息

批准号：
7512069
负责人：
Virginia Ann Folcik Nivar
金额：
$ 21.5万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-01 至 2011-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7512069
关键词：
Acute Air Air Sacs Alveolar Alveolus Animal Model Apoptotic Architecture Arts Asbestos Autoimmune Process Autopsy Bacterial Infections Behavior Behavioral Biological Biological Process Biomedical Research Bleomycin Blood Vessels Blood capillaries Breathing Cell Line Cell Nucleus Cells Cessation of life Characteristics Chemicals Chronic Clinical Clinical Trials Collagen Complex Computer Simulation Computers Computing Methodologies Connective Tissue Diseases Death Rate Defect Diagnosis Disease Disease Progression Dust Effectiveness of Interventions Endothelial Cells Endothelium Engineering Enzymes Epithelial Epithelial Cells Equilibrium Erythrocytes Fibroblasts Fibrosis Future Gases Gene Expression Regulation Generic Drugs Goals Hamman-Rich syndrome Heart failure Human Hyperplasia Immune Immune response Immune system Immunologist In Vitro Inherited Injury Interstitial Lung Diseases Intervention Investigation Irritants Knowledge Laboratories Lead Learning Left Life Literature Logic Lung Lung diseases Medicine Methods Mining Modeling Movement Mus Myofibroblast Occupational Organ Organism Outcome Output Oxygen Particulate Pathologist Pathology Patients Pattern Phase Pollution Prevention Principal Investigator Process Proliferating Proteins Publishing Pulmonary Fibrosis Reaction Recruitment Activity Red nucleus structure Research Research Methodology Science Signal Transduction Silicon Dioxide Simulate Smoke Solutions Source Specimen Staining method Stains Structure of parenchyma of lung System Testing Time Tissues Translating Trichrome stain Viral Virtual Tool Vision Wound Healing base capillary capillary bed cell behavior cell type chemokine chemotherapy cost cytokine experience granulocyte human disease improved information gathering inhibitor/antagonist injured injury and repair innovation insight interest knowledge base locus ceruleus structure lung injury macrophage multidisciplinary pneumocyte pressure prevent programs public health relevance repaired research study response response to injury simulation success successful intervention theories tool virtual

项目摘要

DESCRIPTION (provided by applicant): A computer simulation of lung disease will be created to be a tool for virtual experimentation. It will incorporate what is known about the complex biological processes involved in lung injury and repair and apply it to the analysis of acute and chronic, fibrotic, interstitial lung diseases. The simulation process is called agent-based modeling, a state of the art method for logical computational modeling(1-4). This dynamic model will explore the possible causes of interstitial lung disease(s) including idiopathic (the cause is unknown) pulmonary fibrosis (IPF), an untreatable and deadly lung disease(5). Although IPF is rare, the death rate is increasing [55.1 deaths/106 in 2003; (6)]. There are numerous theories about the causes of IPF, but no cure is in sight(7). There are several forms of pulmonary fibrosis (PF), some are chronically debilitating and others may be overcome with treatment(8). There is enough understanding to diagnose the form of the disease after its onset. The pharmaceutically controllable forms of PF provide information about mechanisms that do not propagate IPF, and years of experimentation with animal models and in- vitro studies also provide information that will be integrated into the computer simulation. This computer simulation will be an extension of an existing, validated, published and publicly available, agent-based simulation of the immune system, created by the principal investigator (9). This multidisciplinary group of pulmonologists, a pulmonary pathologist, a murine PF modeler and an immunologist/computer modeler will condense relevant information about lung diseases and lung repair mechanisms into a (logical, plain English) form that can be programmed into the computer model. Al of the lung cells and cytokines/chemokines involved will be represented. This is an activity that rarely occurs in the world of biomedical research, the combination of existing information to gain insight into the system as a whole. Agent-based modeling was invented for this purpose, to analyze complex systems (like the lung and immune systems) using information gathered about the parts of the system via the traditional laboratory and clinical approaches. The simulation will be validated by comparison of the behavior (and output) from the simulated injured lung to existing pathology specimens with known diagnosis and outcomes from human patients. Simulation parameters will be adjusted iteratively [using indirect parameterization(3)] until the simulation output is comparable to disease patterns with known cause and effect. Then the numerous postulated causes for IPF will be tested to determine if any of them cause patterns of simulated lung cell behavior that emulate real disease processes. Everyone involved will benefit from the learning experience that agent-based modeling provides. More importantly, virtual experimentation will provide insight into an incurable disease that attacks people in their prime, and will provide information that indicates potential strategies for successful intervention. PUBLIC HEALTH RELEVANCE: The time has come for the scientific information that exists about incurable lung diseases such as pulmonary fibrosis to be compiled and analyzed using the latest computational methods. Computational modeling based on logic will be used to analyze the existing, abundant scientific knowledge base and generate logical conclusions about plausible causes for these debilitating lung diseases. This approach can help determine what interventions may potentially be employed for their prevention or cure.

描述（由申请人提供）：将创建肺部疾病的计算机模拟作为虚拟实验的工具。它将结合有关肺损伤和修复的复杂生物过程的已知知识，并将其应用于急性和慢性、纤维化、间质性肺疾病的分析。该模拟过程称为基于代理的建模，这是一种最先进的逻辑计算建模方法(1-4)。该动态模型将探讨间质性肺疾病的可能原因，包括特发性（原因未知）肺纤维化 (IPF)，这是一种无法治疗的致命肺部疾病(5)。虽然IPF很少见，但死亡率正在上升[2003年为55.1人/106人； (6)]。关于 IPF 的病因有多种理论，但尚无治愈方法(7)。肺纤维化 (PF) 有多种形式，其中一些会导致慢性衰弱，另一些则可以通过治疗来克服(8)。对疾病发病后的形式有足够的了解来诊断。药物可控的 PF 形式提供了有关不传播 IPF 的机制的信息，并且多年的动物模型实验和体外研究也提供了将集成到计算机模拟中的信息。该计算机模拟将是由首席研究员创建的现有的、经过验证的、已发布的和公开的、基于代理的免疫系统模拟的扩展 (9)。这个由肺病学家、肺病理学家、小鼠肺纤维化建模师和免疫学家/计算机建模师组成的多学科小组将把有关肺部疾病和肺修复机制的相关信息浓缩成可以编程到计算机模型中的（逻辑的、简单的英语）形式。将代表所有涉及的肺细胞和细胞因子/趋化因子。这是生物医学研究领域很少发生的活动，结合现有信息来深入了解整个系统。基于代理的建模就是为此目的而发明的，利用通过传统实验室和临床方法收集的有关系统各部分的信息来分析复杂系统（如肺和免疫系统）。将通过比较模拟受伤肺部的行为（和输出）与已知人类患者的诊断和结果的现有病理标本来验证模拟。模拟参数将迭代调整[使用间接参数化(3)]，直到模拟输出与已知因果关系的疾病模式相当。然后，将测试 IPF 的众多假设原因，以确定其中是否有任何原因会导致模拟真实疾病过程的模拟肺细胞行为模式。每个参与者都将从基于代理的建模提供的学习经验中受益。更重要的是，虚拟实验将深入了解一种攻击壮年人的不治之症，并将提供表明成功干预的潜在策略的信息。公共健康相关性：现在是时候使用最新的计算方法来汇编和分析有关肺纤维化等无法治愈的肺部疾病的科学信息了。基于逻辑的计算模型将用于分析现有的、丰富的科学知识库，并就这些使人衰弱的肺部疾病的合理原因得出逻辑结论。这种方法可以帮助确定可能采用哪些干预措施来预防或治疗它们。