HIFI

HIFI infers high-resolution intra-chromosomal DNA-DNA interaction frequencies from Hi-C data at restriction-fragment (RF) resolution to reconstruct interaction frequency matrices and mitigate limitations from insufficient sequencing depth.

Key Features:

• Adaptive kernel density estimation and Markov Random Field approaches: HIFI applies adaptive kernel density estimation and Markov Random Field methods to infer true intra-chromosomal interaction frequencies from sparse Hi-C read-count matrices.
• Exploitation of fragment dependencies: HIFI leverages dependencies between neighboring restriction fragments to enhance resolution beyond what is achievable with typical sequencing depths.
• Cross-validation and comparative analysis: Performance has been assessed by cross-validation and by comparison to 5C data and known regulatory interactions to evaluate accuracy at restriction-fragment resolution.

Scientific Applications:

• Chromosome three-dimensional architecture: Provides high-resolution interaction matrices for studying the three-dimensional organization of chromosomes.
• Regulatory region and TAD analysis: Enables investigation of how active regulatory regions contribute to structuring topologically associating domains (TADs).
• Gene regulation and genome stability: Facilitates analysis of DNA-DNA interactions relevant to gene regulation and genome stability.

Methodology:

HIFI applies adaptive kernel density estimation and Markov Random Field approaches to sparse Hi-C read-count matrices, leverages neighboring restriction-fragment dependencies, and employs cross-validation plus comparisons to 5C data and known regulatory interactions for validation.