Transfer Rule Learning with Functional Mapping for Integrative Modeling of Panomics Data

具有功能映射的转移规则学习用于全景数据的集成建模

• 批准号: 9246538
• 负责人: Vanathi Gopalakrishnan
• 金额: $ 28.9万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-24 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9246538
• 关键词: Affect; Bacteria; Biological; Biological Markers; Cause of Death; Classification; Communicable Diseases; Communities; Computer Simulation; Computing Methodologies; DNA Methylation; Data; Data Set; Detection; Diagnosis; Disease; Disease Management; Disease model; Early Diagnosis; Fostering; Gene Expression; Genes; Health; Helminths; Human; Human Microbiome; Indonesia; Infection; Ivory Coast; Knowledge; Lead; Learning; Liberia; Link; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Maps; Measures; Medicine; Methods; Modeling; Molecular Profiling; Monitor; Nodule; Ontology; Outcome; Output; Parasites; Parasitic infection; Patients; Pattern; Performance; Phylogenetic Analysis; Population; Probiotics; Psychological Transfer; Research; Ribosomal RNA; Sampling; Source; Structure; Taxonomy; Testing; The Cancer Genome Atlas; Treatment outcome; Trees; United States; Validation; base; biomarker discovery; biomarker panel; cancer biomarkers; cancer classification; case control; cohort; computerized tools; design; disease classification; global health; high risk; high throughput technology; improved; innovation; insight; learning strategy; microbiome; microbiota; novel; precision medicine; predictive modeling; prototype; public health relevance; screening; tool

 DESCRIPTION (provided by applicant): Molecular profiling data from scientific studies aiming for early detection and better management of diseases such as cancer, has accumulated at rates far beyond our abilities to efficiently extract knowledge of value to the practice of precisin medicine. A major challenge is that these data are often generated using multiple high-throughput technologies giving rise to panomics data such as gene expression and DNA methylation for the same or related classification task. This project will develop critically neede computational methods and tools for the integrative modeling of panomics data to improve disease state classification from related molecular profiling studies. This project will extend Transfer Rule Learning (TRL) methods that were previously developed to deal with sparse data from biomarker profiling studies, by automatically learning classification rules from one dataset, transferring that knowledge and using it when learning rules from a related dataset. This project will develop, apply and evaluate a novel method for knowledge transfer that involves the use of ontological or taxonomic hierarchies along with classification rule learning. Specifically, this project will test the hypothesis that transfer learning of classification rules using functional mapping (TRL-FM) via ontological structure to provide domain-specific relatedness improves integrative modeling of panomics data over conventional methods to yield better predictive performance and identify more robust biomarker panels for disease state classification. The TRL-FM prototype will be applied to existing de-identified panomics data from two diverse domains for the classification of (1) cancer, and (2) parasitic infections in global populations using microbiome profiling. The TRL-FM models will be validated for precise lung cancer classification and robust biomarker discovery, using an existing set of de-identified panomics data and related nodule size information from a cohort of high-risk CT-screened patients, and comprehensively compared to state-of-the-art classifiers. This project can help create more robust screening tools for the precise classification of lung cancer, the leading cause of death from cancer in the United States. This project will also impact global health with the potential to help improve screening and management of infections caused by helminths, the most common parasites affecting more than a billion people worldwide, using data obtained from fecal microbiome profiling. This project will result in computational tools that can efficiently integrat knowledge from multiple sources when building predictive models from panomics data. The predictive models are highly interpretable, capturing patterns that underlie subpopulations in the data, as classification rules with augmented information about the robustness of discriminative biomarkers. This project will create tools to benefit the rapidly growing human microbiome research community, by incorporating knowledge specific to the analyses of bacterial species sequenced from ribosomal RNA. The TRL-FM tools will make integrative modeling of microbiome data more efficient thereby enabling rapid insights into bacterial strains and species that harm or support human health.

 描述（由申请人提供）：旨在早期发现和更好地管理癌症等疾病的科学研究的分子分析数据的积累速度远远超出了我们有效提取对精准医学实践有价值的知识的能力。这些数据通常是使用多种高通量技术生成的，从而产生用于相同或相关分类任务的基因表达和 DNA 甲基化等泛组学数据。该项目将为集成建模开发急需的计算方法和工具。该项目将扩展以前开发的用于处理生物标志物分析研究的稀疏数据的转移规则学习（TRL）方法，通过从一个数据集中自动学习分类规则，并将其转移。该项目将开发、应用和评估一种新的知识转移方法，该方法涉及使用本体论或分类层次结构以及分类规则学习。的迁移学习通过本体结构使用功能映射（TRL-FM）的分类规则可提供特定领域的相关性，与传统方法相比，可以改进全景组学数据的综合建模，从而产生更好的预测性能，并为疾病状态分类识别更强大的生物标志物组。 TRL-FM 模型将应用于来自两个不同领域的现有去识别全景组学数据，以使用微生物组分析对（1）癌症和（2）全球人群中的寄生虫感染进行分类。TRL-FM 模型将针对精确的肺癌进行验证。分类和强大的生物标志物发现，使用一组现有的去识别的全景组学数据和来自一组高危 CT 筛查患者的相关结节大小信息，并与最先进的分类器进行全面比较。该项目可以提供帮助。创建更强大的筛查工具来精确分类肺癌，这是美国癌症死亡的主要原因。该项目还将影响全球健康，并有可能影响全球健康。 利用从粪便微生物组分析中获得的数据，帮助改进对蠕虫引起的感染的筛查和管理，蠕虫是最常见的寄生虫，影响着全球超过十亿人。该项目将产生计算工具，在构建预测模型时可以有效地整合来自多个来源的知识。预测模型具有高度可解释性，可以捕获数据中亚群的模式，作为带有有关判别性生物标志物稳健性的增强信息的分类规则。通过整合从核糖体 RNA 测序的细菌物种分析的特定知识，TRL-FM 工具将使微生物组数据的综合建模更加有效，从而能够快速了解​​损害或支持人类健康的细菌菌株和物种。 。