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Relationship between spatial organization and biological function, analyzed using gene ontology and chromosome conformation capture of human and fission yeast genomes

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Abstract

Cells regulate functionally related genes cis- and trans-contacts in order to perform specific biological roles. To understand the cryptic spatial genomic contexts underlying these biological functions, we analyzed the gene association data from the gene ontology (GO) database and the genomic spatial organization data obtained by analysis of chromosome conformation capture (3C)-based data from the Sequence Read Archive, where GO and 3C-based data were used to measure functional similarity and spatial proximity, respectively, between genomic loci. In the human genome and the fission yeast genome, we observed that correlation between the two measures was statistically significant on a genome-wide scale. Specifically, it is also confirmed that the genomic spatial architecture is affected by functional similarity of genes by showing better correlation of functional similarities with spatial distances estimated by contact frequencies than those estimated by genomic distances for cis-contacts. Furthermore, we analyzed distances between the genomic segments sharing the same GO term using the two-sample t test, found that the genomic segments identified by various GO terms are spatially located closer than the average distance over statistically-valid contacts, and provided a list of the GO terms. The results suggested that genomic loci with similar biological functions are situated in close proximity to each other in the nuclear space by aggregating functionally related genes in a short spatial range.

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Acknowledgments

This work was supported by the Stem Cell Research Program (grant no. 2012M3A9B4027957), the Korea Healthcare technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (grant no. A092006), the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (grant no. NRF-2010-0012649), and the National Research Foundation of Korea grant funded by the Korea Government (MEST) (grant no. 2009-0086964).

Authors’ contributions

Study design: SH, DK. Analyses of data: SH. Writing manuscript: SH, DK. All authors read and approved the final manuscript.

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  1. Department of Chemistry, Chung-Ang University, Seoul, 156-756, South Korea

    Seungsoo Hahn

  2. Department of Bio and Brain Engineering, KAIST, Daejeon, 305-701, South Korea

    Dongsup Kim

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  1. Seungsoo Hahn
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Seungsoo Hahn declares that they have no conflict of interest. Dongsup Kim declares that they have no conflict of interest.

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Hahn, S., Kim, D. Relationship between spatial organization and biological function, analyzed using gene ontology and chromosome conformation capture of human and fission yeast genomes. Genes Genom 38, 693–705 (2016). https://doi.org/10.1007/s13258-016-0413-7

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