Robust Hierarchical Finite Mixture Modeling of Collagen Fibril Diameters
胶原原纤维直径的鲁棒分层有限混合建模
基本信息
- 批准号:7388220
- 负责人:
- 金额:$ 19.6万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-04-01 至 2010-02-28
- 项目状态:已结题
- 来源:
- 关键词:AccountingAddressAgingAlgorithmsAnimalsAppendixAttentionBiologicalCaliberCharacteristicsClassCollagenCollagen FibrilComputer softwareComputing MethodologiesDataData AnalysesDatabasesDevelopmentEquationExtracellular MatrixGillsGoalsGrantGrowthGrowth and Development functionIndividualInvestigationKnowledgeLateralMeasurementMeasuresMedicalMethodologyMethodsMicroscopicModalityModelingMusNatural regenerationNormal Statistical DistributionNumbersOperative Surgical ProceduresPerformanceProceduresProcessPropertyProteoglycanPurposeRangeRegulationResearchRoleSamplingShapesSimulateStagingStandards of Weights and MeasuresStatistical MethodsStatistical ModelsStudy SectionTendon structureTestingTimeTransgenic Organismsbasebiglycandata structuredecorindensityfibrillogenesisfibromodulinindexinginjury and repairinsightlumicanmature animalmembermouse modelnovelrepairedsimulationtheoriestool
项目摘要
DESCRIPTION (provided by applicant): Extracellular matrix assembly is a multi-step process, with each step requiring specific regulatory interactions. Definition of the steps in matrix assembly and the mechanisms regulating them will enhance our understanding of tendon development, growth, repair and pathological changes associated with aging or injury and repair/regeneration after wounding or surgical intervention. The mechanisms involved in tendon extracellular matrix assembly are investigated, in part, by studying decomposition of the fibril diameter distributions into subpopulations with different characteristics and functional roles. Therefore, statistical modeling of fibril diameters as finite mixtures of normal subpopulations provides insight into the mechanisms regulating collagen fibrillogenesis. The overall goal of this application is to develop robust one-objective-function estimation methods and corresponding software for fitting a hierarchical random effects model with multiple levels of random effects and conditional distributions modeled as finite mixtures of normal components. This methodology will provide a framework for novel and efficient statistical analysis of the collagen fibril diameters data generated by the ongoing study Regulated Assembly of Tendon Extracellular Matrix (NIH/NIAMSD R01AR44745) and similar studies of collagen fibrillogenesis. While statistical methodology that will be developed is geared toward the needs of robust and efficient analyses of collagen fibril diameter distributions, the proposed models and estimation methods are very general, and will be useful for analyses of most general clustered biological data. The proposed studies will (1) extend statistical methodology and software to generate novel models and develop corresponding maximum likelihood and robust estimation methods for multilevel clustered data with conditional distributions represented by finite mixtures of normal components; (2) investigate the statistical properties of the proposed models using simulations; (3) compare the performance of the maximum likelihood and robust with respect to outliers estimation methods for modeling conditional collagen fibril diameter distributions as finite mixtures of normal components; (4) analyze extensive data from the study of tendon collagen fibrillogenesis using the proposed hierarchical random effects model and robust estimating approaches that are found optimal for fibril diameters data. The studies of collagen fibril development are important for our understanding of growth, repair and pathological changes associated with aging or injury and repair/regeneration after wounding or surgical intervention. The mechanisms of fibril development may be studied by decomposing the fibril diameter distributions into subpopulations with different characteristics and functional roles. This project focuses on developing novel statistical methods for analyses of such decompositions.
描述(由申请人提供):细胞外基质组装是一个多步骤过程,每个步骤都需要特定的监管相互作用。基质组装步骤的定义和调节它们的机制将增强我们对肌腱发育、生长、修复和与衰老或损伤相关的病理变化以及创伤或手术干预后的修复/再生的理解。肌腱细胞外基质组装的机制进行了研究,部分,通过研究分解成亚群的原纤维直径分布具有不同的特点和功能的作用。因此,作为正常亚群的有限混合物的原纤维直径的统计建模提供了对调节胶原原纤维形成的机制的深入了解。本申请的总体目标是开发稳健的单目标函数估计方法和相应的软件,用于拟合具有多水平随机效应和条件分布的分层随机效应模型,该模型建模为正态分量的有限混合物。该方法将为正在进行的肌腱细胞外基质调节组装研究(NIH/NIAMSD R 01 AR 44745)和胶原纤维发生的类似研究生成的胶原纤维直径数据的新型有效统计分析提供框架。虽然将开发的统计方法是面向强大的和有效的分析胶原纤维直径分布的需要,所提出的模型和估计方法是非常一般的,并将是有用的分析最一般的聚类生物数据。本文的研究将(1)扩展统计方法和软件以生成新的模型,并为具有正态成分的有限混合表示的条件分布的多层聚类数据开发相应的最大似然和稳健估计方法;(2)使用模拟研究所提出的模型的统计特性;(3)比较最大似然和鲁棒相对于用于将条件胶原原纤维直径分布建模为正态分量的有限混合物的离群值估计方法的性能;(4)使用所提出的分层随机效应模型和稳健估计方法分析来自肌腱胶原纤维形成研究的大量数据,发现这些方法对于纤维直径数据是最佳的。胶原纤维发育的研究对于我们理解与衰老或损伤相关的生长、修复和病理变化以及创伤或手术干预后的修复/再生具有重要意义。通过将纤维直径分布分解为具有不同特征和功能作用的亚群,可以研究纤维发育的机制。该项目的重点是开发新的统计方法,分析这种分解。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Generalized weighted likelihood density estimators with application to finite mixture of exponential family distributions.
- DOI:10.1016/j.csda.2010.05.013
- 发表时间:2011-01-01
- 期刊:
- 影响因子:1.8
- 作者:Zhan T;Chevoneva I;Iglewicz B
- 通讯作者:Iglewicz B
Constrained S-estimators for linear mixed effects models with covariance components.
用于具有协方差分量的线性混合效应模型的约束 S 估计器。
- DOI:10.1002/sim.4169
- 发表时间:2011
- 期刊:
- 影响因子:2
- 作者:Chervoneva,Inna;Vishnyakov,Mark
- 通讯作者:Vishnyakov,Mark
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Inna Chervoneva其他文献
Inna Chervoneva的其他文献
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8288712 - 财政年份:2011
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Semiparametric Methods for Efficiency-Adjusted Relative qRT-PCR Quantification
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Robust Hierarchical Finite Mixture Modeling of Collagen Fibril Diameters
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