GWYRE: A Resource for Mapping Variants onto Experimental and Modeled Structures of Human Protein Complexes.

Rapid progress in structural modeling of proteins and their interactions is powered by advances in knowledge-based methodologies along with better understanding of physical principles of protein structure and function. The pool of structural data for modeling of proteins and protein-protein complexes is constantly increasing due to the rapid growth of protein interaction databases and Protein Data Bank. The GWYRE (Genome Wide PhYRE) project capitalizes on these developments by advancing and applying new powerful modeling methodologies to structural modeling of protein-protein interactions and genetic variation. The methods integrate knowledge-based tertiary structure prediction using Phyre2 and quaternary structure prediction using template-based docking by a full-structure alignment protocol to generate models for binary complexes. The predictions are incorporated in a comprehensive public resource for structural characterization of the human interactome and the location of human genetic variants. The GWYRE resource facilitates better understanding of principles of protein interaction and structure/function relationships. The resource is available at http://www.gwyre.org.

Feline degenerative joint disease: a genomic and proteomic approach.

The underlying disease mechanisms for feline degenerative joint disease (DJD) are mostly unidentified. Today, most of what is published on mammalian arthritis is based on human clinical findings or on mammalian models of human arthritis. However, DJD is a common occurrence in the millions of domestic felines worldwide. To get a better understanding of the changes in biological pathways that are associated with feline DJD, this study employed a custom-designed feline GeneChip, and the institution's unique access to large sample populations to investigate genes and proteins from whole blood and serum that may be up- or down-regulated in DJD cats. The GeneChip results centered around three main pathways that were affected in DJD cats: immune function, apoptosis and oxidative phosphorylation. By identifying these key disease-associated pathways it will then be possible to better understand disease pathogenesis and diagnose it more easily, and to better target it with pharmaceutical and nutritional intervention.

Sequencing and comparative genomic analysis of 1227 Felis catus cDNA sequences enriched for developmental, clinical and nutritional phenotypes.

BACKGROUND: The feline genome is valuable to the veterinary and model organism genomics communities because the cat is an obligate carnivore and a model for endangered felids. The initial public release of the Felis catus genome assembly provided a framework for investigating the genomic basis of feline biology. However, the entire set of protein coding genes has not been elucidated. RESULTS: We identified and characterized 1227 protein coding feline sequences, of which 913 map to public sequences and 314 are novel. These sequences have been deposited into NCBI's genbank database and complement public genomic resources by providing additional protein coding sequences that fill in some of the gaps in the feline genome assembly. Through functional and comparative genomic analyses, we gained an understanding of the role of these sequences in feline development, nutrition and health. Specifically, we identified 104 orthologs of human genes associated with Mendelian disorders. We detected negative selection within sequences with gene ontology annotations associated with intracellular trafficking, cytoskeleton and muscle functions. We detected relatively less negative selection on protein sequences encoding extracellular networks, apoptotic pathways and mitochondrial gene ontology annotations. Additionally, we characterized feline cDNA sequences that have mouse orthologs associated with clinical, nutritional and developmental phenotypes. Together, this analysis provides an overview of the value of our cDNA sequences and enhances our understanding of how the feline genome is similar to, and different from other mammalian genomes. CONCLUSIONS: The cDNA sequences reported here expand existing feline genomic resources by providing high-quality sequences annotated with comparative genomic information providing functional, clinical, nutritional and orthologous gene information.