Deciphering the association between gene function and spatial gene-gene interactions in 3D human genome conformation.
Deciphering the association between gene function and spatial gene-gene interactions in 3D human genome conformation.
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DOI：
10.1186/s12864-015-2093-0
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发表时间：
2015-10-28
期刊：
影响因子：
4.4
通讯作者：
Cheng J
中科院分区：
文献类型：
--
作者：
Cao R;Cheng J
在基因功能预测和分析的背景下，已经研究了许多因素，如序列同一性、基因表达和基因共同进化。然而，基因组的三维构象还没有被用来分析基因功能，这在很大程度上可能是因为直到最近才缺乏基因组构象数据。我们从Hi-C染色体构象捕获技术产生的染色体接触数据中构建了三个不同人类B细胞或细胞系的全基因组空间基因-基因相互作用网络。G-SESAME和Fast-SemSim用于计算互作/非互作基因之间的功能相似度。从基因-基因相互作用网络计算出的基因本体论统计量用于基因功能预测。我们比较了空间上没有相互作用的基因对和有相互作用的基因对的功能相似性。我们发现，空间相互作用强的基因往往在生物学过程、分子功能和基因本体的细胞组成方面具有高度相似的功能。尽管基因-基因相互作用的水平通常与序列基因组距离或基因间序列同一性没有或弱相关，但功能相似性高的相互作用基因往往具有更强的相互作用，略短的基因组距离和显著更高的序列同一性。在基因功能分析中，将基因组距离或序列同一性与空间基因-基因互作信息相结合比单独使用其中任何一个信息更能揭示基因-基因功能相似性，表明基因-基因互作信息在很大程度上与基因组距离和序列同一性具有互补性。我们开发并评估了一种基于基因-基因相互作用网络的基因功能预测方法，该方法可以很好地预测大量人类基因的功能。在这项工作中，我们证明了人类基因组的空间构象与基因功能相似性有关，并有助于基因功能预测。本文的在线版本(doi：10.1186/s12864-0152093-0)包含补充材料，可供授权用户使用。
A number of factors have been investigated in the context of gene function prediction and analysis, such as sequence identity, gene expressions, and gene co-evolution. However, three-dimensional (3D) conformation of the genome has not been tapped to analyse gene function, probably largely due to lack of genome conformation data until recently. We construct the genome-wide spatial gene-gene interaction networks for three different human B-cells or cell lines from their chromosomal contact data generated by the Hi-C chromosome conformation capturing technique. The G-SESAME and Fast-SemSim are used to calculate function similarity between interacted / non-interacted genes. The Gene Ontology statistics computed from the gene-gene interaction networks is used for gene function prediction. We compare the function similarity of gene pairs that do not spatially interact and that have interactions. We find that genes that have strong spatial interactions tend to have highly similar function in terms of biological process, molecular function and cellular component of the Gene Ontology. And even though the level of gene-gene interactions generally have no or weak correlation with either sequential genomic distance or sequence identity between genes, the interacted genes with high function similarity tend to have stronger interactions, somewhat shorter genomic distance and significantly higher sequence identity. And combining genomic distance or sequence identity with spatial gene-gene interaction information informs gene-gene function similarity much better than using either one of them alone, suggesting gene-gene interaction information is largely complementary with genomic distance and sequence identity in the context of gene function analysis. We develop and evaluate a new gene function prediction method based on gene-gene interacting networks, which can predict gene function well for a large number of human genes. In this work, we demonstrate that the spatial conformation of the human genome is relevant to gene function similarity and is useful for gene function prediction. The online version of this article (doi:10.1186/s12864-015-2093-0) contains supplementary material, which is available to authorized users.