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Quantitative transcriptome and proteome maps of classical nonclinical species [b1]

ABSTRACT: The distribution of expression of target genes can provide insights that advance understanding of target availability to aid therapeutic development purposes. The increase of use of biologics and novel modalities, combined with the opportunities of alternative to in vivo experimental methods in safety evaluation of new therapeutics. A detailed understanding of expression levels in target tissues is essential to selecting nonclinical species with the highest translational potential. We quantified the relative RNA and proteinlevels across more than 40 normal tissues and 5 nonclinical species several tissues in human. We identified patterns of cross-species and methodology relationships that can aid in the broader understanding of nonclinical experimental design. We observedexpression profile similarity across tissues that favors species similarity, except for select nervous system and immune tissues. In exploring tissue specificity, we identified ubiquitous transcripts that encode tissue-specific proteins. We also assessed discordance between RNA and protein enrichment and revealed potential sites of synthesis and action of secreted proteins. These data and their relationships are foundational assets in toxicology study design and provide insights into biological regulation in drug discovery.

ORGANISM(S): Mus musculus Rattus norvegicus Sus scrofa Canis lupus familiaris Homo sapiens Macaca fascicularis

PROVIDER: GSE325522 | GEO | 2026/03/25

REPOSITORIES: GEO

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Project description:PFGRC has developed a cost effective alternative to complete genome sequencing in order to study the genetic differences between closely related species and/or strains. The comparative genomics approach combines Gene Discovery (GD) and Comparative Genomic Hybridization (CGH) techniques, resulting in the design and production of species microarrays that represent the diversity of a species beyond just the sequenced reference strain(s) used in the initial microarray design. These species arrays may then be used to interrogate hundreds of closely related strains in order to further unravel their evolutionary relationships. Infectious diarrhea is a leading worldwide cause of infant mortality and secondary malnutrition. Enterotoxigenic E. coli (ETEC) is a principal etiology of travelers?diarrhea and a major endemic health threat, especially among children in developing nations where it is estimated to cause hundreds of thousands of deaths each year. Vaccine development for ETEC has been significantly hampered by the remarkable genetic plasticity of E. coli, a comparatively modest understanding of the basic pathogenesis of these organisms, and an uncertainty regarding the degree to which any given antigenic target might be conserved. While experimental and epidemiologic data suggest that a broadly protective vaccine can be achieved, this will most effectively be accomplished in a research environment that fosters sharing of vital resources and open, collaborative interactions among multiple investigators. The proposed project is aimed at providing critical leverage to ongoing international investigative efforts pertaining to ETEC pathogenesis and vaccinology. The flow of genetic information within this group motivated us to identify novel genes for the purpose of creating a species DNA microarray to better understand the ancestral relationships among its members. Based on preliminary MLST genotyping, 11 diverse ETEC strains were selected for sequencing. Sequence information obtained from this project, and from other publicly available sources, led to the development of a comprehensive species microarray for ETEC group members. The availability of the ETEC species DNA microarray has allowed us to carry out a collaborative CGH genotyping project to validate this microarray as well as understand the phylogenomic relationships among members of ETEC group.

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Quantitative transcriptome and proteome maps of classical nonclinical species [b1]

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