GenomeDISCO

GenomeDISCO quantifies concordance between contact maps from chromosome conformation capture experiments, such as Hi-C and HiChIP, to assess reproducibility and biological variation in three-dimensional chromatin organization.

Key Features:

• Concordance Measure: Introduces a concordance measure to assess similarity between pairs of contact maps for evaluating reproducibility and variation.
• Smoothing Technique: Smooths contact maps using random walks on the graph representation of contact matrices to mitigate experimental noise across scales.
• Noise Sensitivity Analysis: Benchmarked on simulated datasets to evaluate sensitivity to various types of noise affecting chromatin contact maps.
• Application Versatility: Methodology generalizes from Hi-C to other chromosome conformation capture assays such as HiChIP.

Scientific Applications:

• Reproducibility Assessment: Evaluates reproducibility of replicate chromosome conformation capture experiments, including Hi-C datasets.
• Comparative Analysis: Distinguishes biological replicates from samples from different cell types and models variation across cellular contexts in large Hi-C collections.

Methodology:

Computes pairwise concordance between contact maps, smooths contact maps via random walks on graph representations of contact matrices, and benchmarks sensitivity using simulated datasets.