<p>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 <i>in vivo</i> 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 protein levels 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 observed expression 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.</p>

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Quantitative transcriptome and proteome maps of classical nonclinical species

  • Elias Oziolor,
  • Liang Xue,
  • Dennis Pelletier,
  • Darien Capunitan,
  • Emi Kimoto,
  • Joel D. Federspiel,
  • Mark Sheehan,
  • Seda Arat,
  • Leah Newman,
  • Gahyun Lee,
  • Jessie Qian,
  • Steven Kumpf,
  • Thomas A. Lanz,
  • Matthew Martin,
  • Nagappan Mathialagan

摘要

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 protein levels 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 observed expression 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.