A STATISTICAL MODEL TO ASSESS (ALLELE-SPECIFIC) ASSOCIATIONS BETWEEN GENE EXPRESSION AND EPIGENETIC FEATURES USING...

Area of Science:

• Genomics
• Bioinformatics
• Statistical Genetics

Background:

• Sequencing techniques like RNA-seq and DNase-seq generate discrete count data, enabling allele-specific signal detection unlike microarrays.
• Epigenetic features and gene expression are interconnected and influenced by DNA polymorphisms.
• Existing models lack the flexibility to jointly analyze gene expression, epigenetic features, and DNA polymorphisms, including their interactions.

Purpose of the Study:

• To develop a flexible statistical model for assessing associations between gene expression and epigenetic features using sequencing data.
• To explicitly model the effects of DNA polymorphisms in allele-specific or non-allele-specific ways.
• To enable the detection of conditional associations between gene expression and epigenetic features, given DNA polymorphisms.

Main Methods:

• Developed a novel statistical model to integrate gene expression and epigenetic data from sequencing experiments.
• Incorporated modeling of DNA polymorphism effects, allowing for allele-specific and non-allele-specific analyses.
• Validated the model's performance through simulations and applied it to real-world data.

Main Results:

• The developed model successfully assesses associations between gene expression and epigenetic features using sequencing data.
• The model can detect conditional associations between gene expression and epigenetic features, considering DNA polymorphisms.
• Application to HapMap data demonstrated the model's utility in studying gene expression and DNase I Hypersensitive sites (DHSs) associations.

Conclusions:

• The new statistical model provides a flexible framework for analyzing complex relationships in sequencing data.
• It allows for a nuanced understanding of how DNA polymorphisms modulate gene expression and epigenetic landscapes.
• The model's generalizability makes it applicable to a wide range of sequencing-based studies, advancing genomic research.