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Analysis of the Relationship Between Co-localization of Proteins in Protein Assemblies and Protein Proximity in 3-D Space Public

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There has been considerable interest in defining the complete set of human protein complexes. Currently, a comprehensive dataset of human protein complexes, hu.MAP ( http://proteincomplexes.org) gives us a valuable source for a better understanding of the core cellular functions of human proteins and helping to know which proteins will work together(Drew et al., 2017). Recently, techniques allowing prediction of three-dimensional (3-D) chromosome and genome structures have become more mature. In particular, Hi-C data, which stores the interaction strength of different sites of each human chromosome, has become increasingly available. Therefore, based on hu.MAP and Hi-C data, we have information both about which genes are found in protein complexes, and the strength of interaction of each pair of genes in those human protein complexes at the level of their encoding DNA. In this work, we hypothesize that no matter whether each pair of interacting genes is located on the same chromosome or not, and no matter how far apart they are genome sequence-wise, when they encode proteins that ends up in the same protein complex, they will be physically closely located in 3-D space. Most of the genes that encode proteins that from the same complex were found to be not on the same chromosome, so we divided them into two groups: occurring either on the same chromosome or occurring on different chromosomes. For each pair of genes in a human protein complex, we randomly generated 100 pairs as a control group, then observed the distributions of the interaction strength of the experimental data and control group for the same chromosome, and the experimental data and control group for the different chromosomes. After that, for the gene pairs located on the same chromosome, we compared those gene pairs with the topologically associating domain (TAD). We found that TAD is the most critical factor affecting the interaction between genes. Whether the interaction between proteins has an effect on the folding of chromosomes in the 3-D space requires a further in-depth study.

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  • etd-3971
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  • 2020
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  • 2020-05-18
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