Profs. Benos (Pitt) and Kaminski (Yale) were awarded by NIH 2.9M over four years to perform genomic analysis to study the tissue and cellular heterogeneity in IPF. Understanding the molecular networks that underlie disease tissue characteristics will lead to better understanding of the disease, its mechanism and will eventually help design more rational, mechanism-based therapeutic interventions. The purpose of this grant is to study tissue characteristics in Idiopathic Pulmonary Fibrosis (IPF), a chronic and progressive lung disease with significant morbidity and mortality, for which at present there is no effective treatment other than lung transplantation. The study will undertake the following specific aims: (1) Identification of the unique genomic and transcriptomics characteristics of histologically defined lung microenvironments. (2) Determination of the cellular contribution to the genomic and epigenomic changes in the IPF lung. (3) Generate a dynamic regulatory model of IPF based on genomic data and perform preliminary experimental validation of model predictions. The data and analyses will be incorporated into a simple, intuitive, web-based interface, IPFmap, that will allow investigators to interactively mine the data, use analytical tools, integrate their own data into these analyses, and provide seamless access to complementary databases enabling development of therapies.