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Genome conformation capture techniques permit a systematic investigation into the functional spatial organization of genomes, including functional aspects like assessing the co-localization of sets of genomic elements. For example, the co-localization of genes targeted by a transcription factor (TF) within a transcription factory. We quantify spatial co-localization using a rigorous statistical model that measures the enrichment of a subset of elements in neighbourhoods inferred from Hi-C data. We also control for co-localization that can be attributed to genomic order. We systematically apply our open-sourced framework,  spatial-mHG , to search for spatial co-localization phenomena in multiple unicellular Hi-C datasets with corresponding genomic annotations. Our biological findings shed new light on the functional spatial organization of genomes, including: In  C .  crescentus , DNA replication genes reside in two genomic clusters that are spatially co-localized. Furthermore, these clusters contain similar gene copies and lay in genomic vicinity to the  ori  and  ter  sequences. In  S .  cerevisae , Ty5 retrotransposon family element spatially co-localize at a spatially adjacent subset of telomeres. In  N .  crassa , both Proteasome lid subcomplex genes and protein refolding genes jointly spatially co-localize at a shared location. An implementation of our algorithms is available online.

The Functional 3D Organization of Unicellular Genomes