OLOGRAM-MODL: mining enriched n-wise combinations of genomic features with Monte Carlo and dictionary learning

Most epigenetic marks, such as Transcriptional Regulators or histone marks, are biological objects known to work together in n-wise complexes. A suitable way to infer such functional associations between them is to study the overlaps of the corresponding genomic regions. However, the problem of the statistical significance of n-wise overlaps of genomic features is seldom tackled, which prevent rigorous studies of n-wise interactions. We introduce OLOGRAM-MODL, which considers overlaps between n ≥ 2 sets of genomic regions, and computes their statistical mutual enrichment by Monte Carlo fitting of a Negative Binomial distribution, resulting in more resolutive P-values. An optional machine learning method is proposed to find complexes of interest, using a new itemset mining algorithm based on dictionary learning which is resistant to noise inherent to biological assays. The overall approach is implemented through an easy-to-use CLI interface for workflow integration, and a visual tree-based representation of the results suited for explicability. The viability of the method is experimentally studied using both artificial and biological data. This approach is accessible through the command line interface of the pygtftk toolkit, available on Bioconda and from https://github.com/dputhier/pygtftk.