Standardized metadata for human pathogen/vector genomic sequences.

High throughput sequencing has accelerated the determination of genome sequences for thousands of human infectious disease pathogens and dozens of their vectors. The scale and scope of these data are enabling genotype-phenotype association studies to identify genetic determinants of pathogen virulence and drug/insecticide resistance, and phylogenetic studies to track the origin and spread of disease outbreaks. To maximize the utility of genomic sequences for these purposes, it is essential that metadata about the pathogen/vector isolate characteristics be collected and made available in organized, clear, and consistent formats. Here we report the development of the GSCID/BRC Project and Sample Application Standard, developed by representatives of the Genome Sequencing Centers for Infectious Diseases (GSCIDs), the Bioinformatics Resource Centers (BRCs) for Infectious Diseases, and the U.S. National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), informed by interactions with numerous collaborating scientists. It includes mapping to terms from other data standards initiatives, including the Genomic Standards Consortium's minimal information (MIxS) and NCBI's BioSample/BioProjects checklists and the Ontology for Biomedical Investigations (OBI). The standard includes data fields about characteristics of the organism or environmental source of the specimen, spatial-temporal information about the specimen isolation event, phenotypic characteristics of the pathogen/vector isolated, and project leadership and support. By modeling metadata fields into an ontology-based semantic framework and reusing existing ontologies and minimum information checklists, the application standard can be extended to support additional project-specific data fields and integrated with other data represented with comparable standards. The use of this metadata standard by all ongoing and future GSCID sequencing projects will provide a consistent representation of these data in the BRC resources and other repositories that leverage these data, allowing investigators to identify relevant genomic sequences and perform comparative genomics analyses that are both statistically meaningful and biologically relevant.

Peptidoglycan recognition proteins Pglyrp3 and Pglyrp4 are encoded from the epidermal differentiation complex and are candidate genes for the Psors4 locus on chromosome 1q21.

Psoriasis is a common inflammatory skin disease caused by genetic and environmental factors, including bacterial and viral infections. Since the skin is in constant contact with commensal and pathogenic microorganisms, we examined well-supported psoriasis genetic linkage intervals to identify genes encoding innate immune pattern recognition proteins that may play a role in pathogenesis. Two peptidoglycan recognition proteins, Pglyrp3 and Pglyrp4, are localized to the Psors4 locus on chromosome 1q21 in a gene cluster known as the epidermal differentiation complex (EDC). We show that these genes are expressed in the skin as well as in germinal centers in the tonsil. We tested 13 SNPs in or near these genes for association with psoriasis in two independent patient collections: a family-based patient set comprised of 375 individuals from 101 families, and a case-control patient collection of 282 patients with moderate to severe psoriasis and 192 healthy controls. In the family-based analysis, several SNPs in the Pglyrp3-Pglyrp4 locus show association with psoriasis (0.01 < P < 0.05). Multiple-SNP haplotypes incorporating Pglyrp3 and Pglyrp4 SNPs also show significant association in the transmission disequilibrium test (TDT; P < 0.01). In the case-control test, none of the SNPs that we tested show association with psoriasis when analyzed in single-SNP or haplotype-based tests. The discordance between the TDT and case-control results suggests that the two populations are significantly different in disease etiology, that the polymorphism responsible for the Psors4 linkage is elsewhere in the Pglyrp locus, or that the causative Psors4 polymorphism is in a location near but not in the Pglyrp locus. These data are consistent with previous reports of association of psoriasis with genes on 1q21, and suggest a role for Pglyrps in skin biology.

Murine peptidoglycan recognition proteins PglyrpIalpha and PglyrpIbeta are encoded in the epidermal differentiation complex and are expressed in epidermal and hematopoietic tissues.

Peptidoglycan recognition proteins (PGRPs or PGLYRPs) are pattern recognition molecules that are found in insects and mammals and are critical for innate immune responses. PGRPs bind peptidoglycan, a ubiquitous component of bacterial cell walls, and are involved in killing bacteria, degrading peptidoglycan, and initiating host defense reactions. Relatively little is known about the four mammalian PGRPs. In this article, we report the sequences of mouse PglyrpIalpha and PglyrpIbeta and provide details of their expression in wild-type mouse tissues. PglyrpIalpha and PglyrpIbeta are encoded within the epidermal differentiation complex on mouse chromosome 3F. Both genes are expressed in epidermal and hematopoietic tissues. PglyrpIbeta is expressed in each of 16 tissues tested, while PglyrpIalpha expression is limited to fewer tissues, including the lung and spleen as well as several tissues of the digestive system. Both proteins are expressed in epithelial cells throughout the gut, and immunohistochemical staining shows expression in salivary glands, the squamous epithelium of the stomach, and the villi of the jejunum. Immunohistochemical staining further shows expression of both PglyrpIalpha and PglyrpIbeta in macrophages in the spleen. PglyrpIalpha is not expressed in resting RAW264.7 macrophage-like cells, but is induced by stimulation with lipopolysaccharide. PglyrpIbeta is constitutively expressed in RAW264.7 cells and is unaffected by lipopolysaccharide or peptidoglycan stimulation. Computational and experimental data suggest that these proteins are secreted. This work provides a step toward understanding the roles of PglyrpIalpha and PglyrpIbeta in host defense and chronic inflammatory conditions induced by bacteria or their components.