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Human interactome
The human interactome is the set of protein-protein interactions (the interactome) that occur in human cells. The sequencing of reference genomes, in particular the Human Genome Project, has revolutionized human genetics, molecular biology, and clinical medicine. Genome-wide association study results have led to the association of genes with most Mendelian disorders, and over 140 000 germline mutations have been associated with at least one genetic disease. However, it became apparent that inherent to these studies is an emphasis on clinical outcome rather than a comprehensive understanding of human disease; indeed to date the most significant contributions of GWAS have been restricted to the “low-hanging fruit” of direct single mutation disorders, prompting a systems biology approach to genomic analysis. The connection between genotype and phenotype (how variation in genotype affects the disease or normal functioning of the cell and the human body) remain elusive, especially in the context of multigenic complex traits and cancer. To assign functional context to genotypic changes, much of recent research efforts have been devoted to the mapping of the networks formed by interactions of cellular and genetic components in humans, as well as how these networks are altered by genetic and somatic disease.
==Background==
With the sequencing of the genomes of a diverse array or model organisms, it became clear that the number of genes does not correlate with the human perception of relative organism complexity – the human proteome contains some 20 000 genes, which is smaller than some species such as corn. A statistical approach to calculating the number of interactions in humans gives an estimate of around 650 000, one order of magnitude bigger than Drosophila and 3 times larger than C. Elegans. As of 2008, only about <0.3% of all estimated interactions among human proteins has been identified, although in recent years there has been exponential growth in discovery – as of 2015, over 210 000 unique human positive protein-protein interactions are currently catalogued, and bioGRID database contains almost 750 000 literature-curated PPI's for 30 model organisms, 300 000 of which are verified or predicted human physical or genetic protein-protein interactions, a 50% increase from 2013. The currently available information on the human interactome network originates from either literature-curated interactions, high-throughput experiments,〔 or from potential interactions predicted from interactome data, whether through phylogenetic profiling (evolutionary similarity), statistical network inference, or text/literature mining methods.
Protein–protein interactions are only the raw material for networks. To form useful interactome databases and create integrated networks, other types of data that can be combined with protein–protein interactions include information on gene expression and co-expression, cellular co-localization of proteins (based on microscopy), genetic information, metabolic and signalling pathways, and more. The end goal of unravelling human protein interactomes is ultimately to understand mechanisms of disease and uncover previously unknown disease genes. It has been found that proteins with a high number of interactions (outward edges) are significantly more likely to be hubs in modules that correlate with disease,〔 probably because proteins with more interactions are involved in more biological functions. By mapping disease alterations to the human interactome, we can gain a much better understanding of the pathways and biological processes of disease.
抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』
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