Systems Biology Approach to Growth Regulation in Cystic Fibrosis

囊性纤维化生长调节的系统生物学方法

• 批准号: 8323482
• 负责人: Mitchell L Drumm
• 金额: $ 38.47万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-20 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8323482
• 关键词: Adipocytes; Adipose tissue; Age; Area; Back; Belief; Biochemical; Biochemical Pathway; Bioinformatics; Biological; Body Size; Body mass index; Cachexia; Cell physiology; Cells; Characteristics; Chronic; Complex; Computer Simulation; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Data; Databases; Diabetes Mellitus; Discipline; Disease; Electrolytes; Endocrine; Endocrine system; Energy Metabolism; Epithelial; Excretory function; Exhibits; Exocrine pancreatic insufficiency; Fingerprint; Functional disorder; Gene-Modified; Genes; Genetic; Genetic Screening; Growth; Health; Height; Homeostasis; Human; Human Genetics; Individual; Infection; Intestines; Link; Liquid substance; Literature; Lung; Lung diseases; Macronutrients Nutrition; Malnutrition; Maps; Measurement; Measures; Messenger RNA; Metabolic; Metabolism; Methods; Modeling; Molecular Biology; Mus; Myeloid Cells; Neurons; Neurosecretory Systems; Obesity; Organ; Outcome; Pathology; Pathway interactions; Patients; Pattern; Physiological; Physiology; Population; Process; Protein Biosynthesis; Pulmonary Function Test/Forced Expiratory Volume 1; Regulation; Resources; Respiratory physiology; Role; Severities; Severity of illness; Signaling Molecule; Smooth Muscle; Sorting - Cell Movement; Surface; Surveys; System; Systems Biology; Technology; Testing; Theoretical model; Tissues; Weight; Work; absorption; base; body system; cystic fibrosis mouse; cystic fibrosis patients; design; falls; genome wide association study; high throughput technology; human disease; indexing; metabolomics; models and simulation; mouse model; nutrition; predictive modeling; pulmonary body; research study; response; uptake

DESCRIPTION (provided by applicant): Individuals afflicted with cystic fibrosis (CF) typically succumb to pulmonary complications of their disease, but CF involves all of the major organ systems. Survival of CF patients correlates strongly with body mass index, and mouse models indicate that body size in CF is due to a complex interaction of neuroendocrine function, adipose metabolism and intestinal function. We will continue to utilize mouse models to elucidate the pathways involved and their interactions, and here we propose a plan that will invoke bioinformatics to extract pathway information from literature and databases and sort out those that are concordant with our empiric data. From those pathways, we will develop computational models that will predict outcomes of these pathways when perturbed in specific ways. Using genetic and pharmacologic methods, we will perturb those pathways and assess how well they predict outcomes. Data from these manipulations will be entered back into the bioinformatics processing and new or revised models will be generated and tested until truly predictive models are generated. Concurrently, a whole-genome association study is being carried out and genes showing association with pulmonary disease or body mass index will be examined to determine if they can be placed on the pathway maps generated by the mouse studies. By this iterative process, we hope to identify new pathways contributing to CF pathophysiology and/or clarify the role of pathways known to influence CF severity.

描述(申请人提供)：囊性纤维化患者通常会死于肺部并发症，但囊性纤维化涉及所有主要器官系统。CF患者的生存与体重指数密切相关，小鼠模型表明，CF患者的身体大小是神经内分泌功能、脂肪代谢和肠道功能复杂相互作用的结果。我们将继续利用小鼠模型来阐明所涉及的路径及其相互作用，这里我们提出了一个计划，将调用生物信息学从文献和数据库中提取路径信息，并筛选出与我们的经验数据一致的路径信息。从这些途径中，我们将开发计算模型，当这些途径受到特定方式的干扰时，将预测这些途径的结果。使用遗传学和药理学方法，我们将扰乱这些途径，并评估它们预测结果的准确性。这些操作的数据将被输入生物信息学处理，并将生成新的或修订的模型并进行测试，直到生成真正的预测模型。与此同时，一项全基因组关联研究正在进行中，显示与肺部疾病或体重指数相关的基因将被检查，以确定它们是否可以放在老鼠研究产生的路径图上。通过这一迭代过程，我们希望找出有助于CF病理生理学的新途径和/或阐明影响CF严重程度的途径的作用。

项目成果

Observation conflict resolution in steady-state metabolic network dynamics analysis.

稳态代谢网络动力学分析中的观察冲突解决。

• DOI: 10.1142/s0219720012400045
• 发表时间: 2012
• 期刊: Journal of bioinformatics and computational biology
• 影响因子: 1
• 作者: Cicek,AErcument;Ozsoyoglu,Gultekin
• 通讯作者: Ozsoyoglu,Gultekin

iPathCase(KEGG): An iPad interface for KEGG metabolic pathways.

• DOI: 10.1186/2047-2501-1-4
• 发表时间: 2013
• 期刊: Health information science and systems
• 影响因子: 6
• 作者: Johnson SR;Qi X;Cicek AE;Ozsoyoglu G
• 通讯作者: Ozsoyoglu G

Model analysis of the relationship between intracellular PO2 and energy demand in skeletal muscle.

细胞内 PO2 与骨骼肌能量需求关系的模型分析。

• DOI: 10.1152/ajpregu.00106.2012
• 发表时间: 2012
• 期刊: American journal of physiology. Regulatory, integrative and comparative physiology
• 作者: Spires,Jessica;Gladden,LBruce;Grassi,Bruno;Saidel,GeraldM;Lai,Nicola
• 通讯作者: Lai,Nicola

Efficient path-based computations on pedigree graphs with compact encodings.

使用紧凑编码对谱系图进行高效的基于路径的计算。

• DOI: 10.1186/1471-2105-13-s3-s14
• 发表时间: 2012
• 期刊: BMC bioinformatics
• 影响因子: 3
• 作者: Yang,Lei;Cheng,En;Özsoyoğlu,ZMeral
• 通讯作者: Özsoyoğlu,ZMeral

Distinguishing the effects of convective and diffusive O₂ delivery on VO₂ on-kinetics in skeletal muscle contracting at moderate intensity.

区分对流和扩散 O2 输送对中等强度骨骼肌收缩中 VO2 动力学的影响。

• DOI: 10.1152/ajpregu.00136.2013
• 发表时间: 2013
• 期刊: American journal of physiology. Regulatory, integrative and comparative physiology
• 作者: Spires,Jessica;Gladden,LBruce;Grassi,Bruno;Goodwin,MatthewL;Saidel,GeraldM;Lai,Nicola
• 通讯作者: Lai,Nicola