NuChart-II: A graph-based approach for analysis and interpretation of Hi-C data

Long-range chromosomal associations between genomic re- gions, and their repositioning in the 3D space of the nucleus, are now considered to be key contributors to the regulation of gene expressions, and important links have been highlighted with other genomic features involved in DNA rearrangements. Recent Chromosome Conformation Capture (3C) measurements performed with high throughput sequenc- ing (Hi-C) and molecular dynamics studies show that there is a large correlation between co-localization and co-regulation of genes, but these important researches are hampered by the lack of biologists-friendly anal- ysis and visualisation software. In this work we present NuChart-II, a software that allows the user to annotate and visualize a list of input genes with information relying on Hi-C data, integrating knowledge data about genomic features that are involved in the chromosome spatial or- ganization. This software works directly with sequenced reads to identify related Hi-C fragments, with the aim of creating gene-centric neighbour- hood graphs on which multi-omics features can be mapped. NuChart-II is a highly optimized implementation of a previous prototype package de- veloped in R, in which the graph-based representation of Hi-C data was tested. The prototype showed inevitable problems of scalability while working genome-wide on large datasets: particular attention has been paid in optimizing the data structures employed while constructing the neighbourhood graph, so as to foster an efficient parallel implementation of the software. The normalization of Hi-C data has been modified and improved, in order to provide a reliable estimation of proximity likelihood for the genes.