Abstract The goal of the Respiratory Computational Discovery Core (Core B) is to provide a collaborative infrastructure in which experienced statisticians and computational and systems biologists will work together to support the various PPG Projects to develop testable hypotheses about genomic features associated with COPD and IPF, and the functional roles of these genes in disease pathogenesis. In this capacity, the Core will serve a dual role. The Core’s analytical team will work closely with the members of the PPG Projects and Cores to design experiments and analyze the resulting data using “conventional” methods, with an emphasis on elucidating the functions of key genes implicated in pulmonary disease. These analyses will be augmented by the development and application of advanced analytical methods aimed at integrating diverse types of data into an interpretable biological framework, providing testable hypotheses regarding drivers of disease progression. The rationale behind creating a separate Core is to supplement the strong quantitative analytical teams working on each of the various Projects with bioinformatics and systems-based modeling expertise and to standardize and integrate data across Projects. In addition, we will develop methods to allow us to more effectively compare results between human and mouse model studies, facilitating the translation of laboratory results into biological and clinical insight that will advance our understanding of the role that key genes, including those involved in mitochondrial and chitinase processes, play in disease development and differentiate COPD and IPF.