Preclinical species gene expression database: Development and meta-analysis.

Area of Science:

• Pharmacology and Toxicology
• Genomics and Bioinformatics
• Comparative Biology

Background:

• Preclinical toxicity studies are crucial for drug safety but limited by cross-species biological differences.
• Interpreting toxicogenomics data is challenging due to a lack of comprehensive preclinical gene expression datasets.
• Advancements in omics data analysis offer potential to predict species-specific differences and enhance toxicology studies.

Purpose of the Study:

• To establish a comprehensive, multi-species, tissue-, and sex-specific gene expression body atlas for widely used preclinical species.
• To facilitate improved interpretation of toxicology data and experimental design in drug development.
• To provide a valuable resource for the scientific community to enhance safety decision-making.

Main Methods:

• RNA-sequencing was performed on approximately 50 tissues from CD1 mice, Sprague Dawley rats, Beagle dogs, and Cynomolgus monkeys (males and females).
• A meta-analysis was conducted on the generated gene expression data to identify species and tissue-specific differences.
• The comprehensive transcriptomic database was made publicly available.

Main Results:

• A large-scale, multi-species preclinical gene expression body atlas was successfully created.
• The meta-analysis highlighted significant species and tissue variations relevant to drug safety.
• The database provides sex-specific gene expression profiles across numerous tissues.

Conclusions:

• This multi-species transcriptomic database is a valuable resource for improving drug safety assessment and experimental design.
• Understanding species-specific gene expression patterns can mitigate risks associated with translating preclinical findings to clinical settings.
• The publicly accessible atlas supports informed safety decision-making across various research disciplines utilizing preclinical models.