GraphTeams: a method for discovering spatial gene clusters in Hi-C sequencing data

Tizian Schulz,Daniel Doerr,Jens Stoye

doi:10.1186/s12864-018-4622-0

Abstract

BackgroundHi-C sequencing offers novel, cost-effective means to study the spatial conformation of chromosomes. We use data obtained from Hi-C experiments to provide new evidence for the existence of spatial gene clusters. These are sets of genes with associated functionality that exhibit close proximity to each other in the spatial conformation of chromosomes across several related species.ResultsWe present the first gene cluster model capable of handling spatial data. Our model generalizes a popular computational model for gene cluster prediction, called δ-teams, from sequences to graphs. Following previous lines of research, we subsequently extend our model to allow for several vertices being associated with the same label. The model, called δ-teams with families, is particular suitable for our application as it enables handling of gene duplicates. We develop algorithmic solutions for both models. We implemented the algorithm for discovering δ-teams with families and integrated it into a fully automated workflow for discovering gene clusters in Hi-C data, called GraphTeams. We applied it to human and mouse data to find intra- and interchromosomal gene cluster candidates. The results include intrachromosomal clusters that seem to exhibit a closer proximity in space than on their chromosomal DNA sequence. We further discovered interchromosomal gene clusters that contain genes from different chromosomes within the human genome, but are located on a single chromosome in mouse.ConclusionsBy identifying δ-teams with families, we provide a flexible model to discover gene cluster candidates in Hi-C data. Our analysis of Hi-C data from human and mouse reveals several known gene clusters (thus validating our approach), but also few sparsely studied or possibly unknown gene cluster candidates that could be the source of further experimental investigations.

Highlights

High-throughput chromosome conformation capture (Hi-C) sequencing offers novel, cost-effective means to study the spatial conformation of chromosomes
We show how δ-teams can be used to find candidate sets of spatial gene clusters using a combination of genome and Hi-C data of two or more species
Our analysis of Hi-C data from human and mouse reveals several known gene clusters, and few sparsely studied or possibly unknown gene cluster candidates that could be the source of further experimental investigation

Summary

Introduction

Hi-C sequencing offers novel, cost-effective means to study the spatial conformation of chromosomes. We use data obtained from Hi-C experiments to provide new evidence for the existence of spatial gene clusters. These are sets of genes with associated functionality that exhibit close proximity to each other in the spatial conformation of chromosomes across several related species. Instances exist where such genes are locally close to each other in the genome, i.e., their positions fall within a narrow region on the same chromosome They may even remain in close proximity over a Schulz et al BMC Genomics 2018, 19(Suppl 5):308 longer evolutionary period, despite the fact that genomes regularly undergo mutations such as genome rearrangements, gene- or segmental duplications, as well as gene insertions and deletions. HOX genes are transcription factors that regulate the embryological development of the metazoan body plan [6]

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Discussion

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