3D modeling of Hi-C contacts: seeing the spatial organization of fungal chromosomes

Abstract

International audienceIn recent years, significant technical advances have been made to better observe the structure and the organization of chromatin. Many Hi-C data are now available in public databases, at different accuracy and resolution and for various species. Generally, the final results of Hi-C data analyses are summarized with the representation of “contact maps”. Using a color scale, these maps (heat-maps) show the frequency of contacts observed between different portions of a genome, both at short-rangeand long-range distances.Even if they are widely used, our observation is that the biological interpretation of contact maps is not trivial. It requires training and significant experience to be useful to validate or invalidate hypotheses concerning the overall organization of the studied genome. In this context, alternative tools have been developed. Some of them produce 3D models ofcontact networks, as a substitute for visualization of Hi-C outputs. By 3D models, we mean representations in a 3D space of a genome, in which euclidean distances are derived from the contact frequency matrices. The information contained in the Hi-C data is thus directly translated into distances in a 3D space. Although care must be taken in interpreting these models (they are not “pictures” of the interior of a cell), we observed they are very helpful to highlight specific structural patterns in chromatin organization, originally hidden in contact maps.Developing new strategies to visualize and integrate large scale multi-omics data is the major objective of Thibault Poinsignon’s thesis (ANR MinOmics). These led us to start building 3D models of yeasts andfilamentous fungi genomes, from Hi-C raw sequencing data. We present here our evaluations of the biological significance and the interest to use these models for projecting heterogeneous epigenomics data and hence better support their biological interpretations