The Establishment Of Human Interactome Resource And The Gene Set Linkage Anlaysis Tool For Multi-species

Next-generation sequencing technology has provided hundreds of thousands of experimental data, along with a variety of analysis tool emerged. Annotation enrichment-based approaches have been widely used in analyzing NGS data, meanwhile, the inherent limitation of these approaches is that they can only observe functions of gene set itself, other than considering that interactions between genes can also contribute to phenotype changes, and also lack of ability to describe new biological phenotypes. For these reasons, we have developed new approaches by measuring the strength of interaction between gene sets to detect whether there are functional linkages between these two gene sets.Gene set linkage analysis needs an interaction network which can cover the majority of the whole interactome. For some species, including Caenorhabditis elegans, Saccharomyces serevisiae, Drosophila melanogaster, the experimental molecular interactions of these species are plenty enough, but other species are not, like Homo sapiens, Arabidopsis thaliana, Oryza sativa, Mus musculus, et al. For these species, we use predicted molecular interaction networks to establish the gene set linkage analysis tool.To achieve a high quality molecular interaction network with high coverage of the whole interactome, we integrated multiple kinds of side evidence, by which means we constructed a molecular interaction network for Homo sapiens, which has high value of precision and specificity.For Homo sapiens and Arabidopsis thaliana, we have established the gene set linkage analysis tool with predicted molecular interaction network, and they have shown good performance in case studies with reported experimental data. To establish the gene set linkage tool for other species, we use experimental interaction network for Caenorhabditis elegans, Saccharomyces serevisiae, Drosophila melanogaster, and predicted interaction network for Oryza sativa, Mus musculus. We evaluated the performance of the gene set linkage tool with reported experimental data, the result shows that compared with other approaches, the gene set linkage analysis tool is more capable than some other tools, it can achieve new biological processes with the expression changed genes in the experiment. Moreover, it can predict new functions of biological meaningful gene set.