Quantitative and qualitative proteome characteristics extracted from in-depth integrated genomics and proteomics...

Area of Science:

• Genomics
• Proteomics
• Systems Biology

Background:

• Protein characteristics are regulated at multiple molecular levels.
• Understanding these regulatory layers is crucial for deciphering biological complexity.

Purpose of the Study:

• To integrate transcriptome and proteome analyses in rat liver.
• To investigate interactions between genomic, transcriptomic, and posttranscriptional regulation.
• To identify molecular drivers of phenotypic diversity, such as hypertension.

Main Methods:

• Quantitative RNA sequencing and mass spectrometry-based proteomics of liver tissues from two rat strains.
• Bioinformatic analysis to identify gene predictions, splice events, protein variants, and RNA editing.
• Multilevel analysis to correlate molecular data and identify regulatory links.

Main Results:

• Peptide evidence for 26,463 rat liver proteins was obtained.
• Validation of numerous gene predictions, splice events, protein variants, and RNA editing events.
• High correlation of quantitative RNA and proteomics data between strains, but poor correlation between data types, indicating significant non-genetic regulation.
• Identification of a genomic variant in the Cyp17a1 promoter potentially linked to hypertension in SHR rats.

Conclusions:

• Integrative multilevel analysis is essential for understanding the genetic control of molecular dynamics.
• Non-genetic factors play a substantial role in regulating protein expression and function.
• This approach can uncover molecular mechanisms underlying complex phenotypes like hypertension.