Genomic/Genetic and Proteome

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ABSTRACT: The Genome and Proteome Core (PPG Core B) will provide essential, cutting-edge genomics, proteomics, and bioinformatics expertise to facilitate the translational impact of this highly integrated PPG. Core B will be respon- sible for providing the research investigators with: (i) expert interrogation of publicly available DNA and RNA sequencing datasets and genome-wide DNA methylome datasets to generate interpretable data from these plat- forms; (ii) genetic expertise needed to test for associations between PPG target gene DNA variants and sus- ceptibility and severity of ARDS; (iii) generation of human endothelial cell (EC) lines and genome-edited cell line models with selected single nucleotide knock in or deletion-based knock out mutations for functional genetic analyses; (iv) execution of traditional proteomic mass spectrometry analysis of immunoprecipitated PPG target proteins for protein translational modification (PTM) identification, including phosphorylation, nitration, and ubiq- uitination; (v) in silico computational protein-structure modeling to identify the impact of functional non-synony- mous coding variants on protein structure and function (protein-protein interaction, catalytic activity, post-trans- lational modification), with protein-protein interactions validated by surface plasmon resonance; and, (vi) exper- tise to oversee production of recombinant proteins with mutations at sites of PTMs or SNPs. As a centralized core for all genome and proteome analyses, Core B (located in Tucson AZ) will perform all relevant analysis of experimental samples for all four projects as each PPG Project will require the services provided by Core B.