Systems Biology of Airway Disease: Core A

Lead PI

Abstract

The primary role of Systems Biology of Airway Disease: Core A – entitled “Systems Biology and Gene Networks” — is to explore in a predictive fashion the molecular and network-based similarities and differences between asthma and COPD. Networks provide frameworks for deriving information from a set of relationships among entities in the program project. We aim to develop tools to identify the disease modules for asthma and COPD, and the molecular relationships between them.

The work will initially rely on the data already collected by the PPG investigators, leading to a first round of mechanistic predictions. These predictions will drive the design of subsequent experimental work and data collection, iteratively improving the Core’s predictive power.

Core A has two specific aims:

Core A will apply network analysis support at different levels: (1) selection and prioritization of the variants and genes associated with airflow obstruction from Project 1; (2) integrating different levels of genomics and transcriptomics data associated with asthma and COPD with the molecular interaction networks (interactome) from Project 2; and (3) identifying and interpreting epigenetic changes (methylation and miRNA) associated with asthma and COPD from Project 3 by integration with protein interactome models. The networks of interactions will serve as a scaffold for information to extract global and local graph theory properties to inform about the initial seed gene choices and about the different “omics” data in Projects 1, 2 and 3.

The interactome-based approach for network building in Core A is critical to our understanding of complex traits such as asthma and COPD. Core A will use genomic elements to build network models to explain the overlap of these diseases. If we can understand this overlap, it will lead to novel therapies and potential cures for these disorders.

Funding

NIH National Heart, Lung, and Blood Institute

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