Abstract
BackgroundStructural interaction frequency matrices between all genome loci are now experimentally achievable thanks to high-throughput chromosome conformation capture technologies. This ensues a new methodological challenge for computational biology which consists in objectively extracting from these data the structural motifs characteristic of genome organisation.ResultsWe deployed the fast multi-scale community mining algorithm based on spectral graph wavelets to characterise the networks of intra-chromosomal interactions in human cell lines. We observed that there exist structural domains of all sizes up to chromosome length and demonstrated that the set of structural communities forms a hierarchy of chromosome segments. Hence, at all scales, chromosome folding predominantly involves interactions between neighbouring sites rather than the formation of links between distant loci.ConclusionsMulti-scale structural decomposition of human chromosomes provides an original framework to question structural organisation and its relationship to functional regulation across the scales. By construction the proposed methodology is independent of the precise assembly of the reference genome and is thus directly applicable to genomes whose assembly is not fully determined.
Highlights
Structural interaction frequency matrices between all genome loci are experimentally achievable thanks to high-throughput chromosome conformation capture technologies
high-throughput chromatin conformation capture data (Hi-C) data can be represented as graphs where nodes represent Deoxyribonucleic acid (DNA) loci and the edges cell line was 5 h 40 mn using Matlab on a linux computing desktop with 8 Xeon CPU at 3.30 GHz
We introduced a fast multi-scale community mining algorithm based on spectral graph wavelets [40] to identify structural motifs from high-throughput chromatin conformation capture data (Hi-C) [10]
Summary
Structural interaction frequency matrices between all genome loci are experimentally achievable thanks to high-throughput chromosome conformation capture technologies. Inspection of intra-chromosomal co-localisation frequency matrices reveals a finer structuring level characterised by diagonal blocks of length ∼ 0.1 − 1 Mb: co-localisation frequency is high between regions of the same block but weaker between regions belonging to different blocks [11] (Fig. 1) These blocks, named Topologically Associating Domains (TADs), underline a structural compartmentalisation of chromosomes whose link with genome functional organisation and dynamics is the subject of intense research activity [11, 15, 16, 19, 20, 23,24,25,26,27,28,29]. Chromosome structural partition was achieved using (i) 1D signals quantifying the balance between the IMR90
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