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Interactome

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Interactome

In molecular biology, an interactome is the whole set of molecular interactions in a particular cell. The term specifically refers to physical interactions among molecules (such as those among proteins, also known as protein–protein interactions, PPIs; or between small molecules and proteins) but can also describe sets of indirect interactions among genes (genetic interactions).

The word "interactome" was originally coined in 1999 by a group of French scientists headed by Bernard Jacq. Mathematically, interactomes are generally displayed as graphs. While interactomes may be described as biological networks, they should not be confused with other networks such as neural networks or food webs.

Molecular interactions can occur between molecules belonging to different biochemical families (proteins, nucleic acids, lipids, carbohydrates, etc.) and also within a given family. Whenever such molecules are connected by physical interactions, they form molecular interaction networks that are generally classified by the nature of the compounds involved. Most commonly, interactome refers to protein–protein interaction (PPI) network (PIN) or subsets thereof. For instance, the Sirt-1 protein interactome and Sirt family second order interactome is the network involving Sirt-1 and its directly interacting proteins where as second order interactome illustrates interactions up to second order of neighbors (Neighbors of neighbors). Another extensively studied type of interactome is the protein–DNA interactome, also called a gene-regulatory network, a network formed by transcription factors, chromatin regulatory proteins, and their target genes. Even metabolic networks can be considered as molecular interaction networks: metabolites, i.e. chemical compounds in a cell, are converted into each other by enzymes, which have to bind their substrates physically.

In fact, all interactome types are interconnected. For instance, protein interactomes contain many enzymes which in turn form biochemical networks. Similarly, gene regulatory networks overlap substantially with protein interaction networks and signaling networks.

It has been suggested that the size of an organism's interactome correlates better than genome size with the biological complexity of the organism. Although protein–protein interaction maps containing several thousand binary interactions are now available for several species, none of them is presently complete and the size of interactomes is still a matter of debate.

The yeast interactome, i.e. all protein–protein interactions among proteins of Saccharomyces cerevisiae, has been estimated to contain between 10,000 and 30,000 interactions. A reasonable estimate may be on the order of 20,000 interactions. Larger estimates often include indirect or predicted interactions, often from affinity purification/mass spectrometry (AP/MS) studies.

Genes interact in the sense that they affect each other's function. For instance, a mutation may be harmless, but when it is combined with another mutation, the combination may turn out to be lethal. Such genes are said to "interact genetically". Genes that are connected in such a way form genetic interaction networks. Some of the goals of these networks are: develop a functional map of a cell's processes, drug target identification using chemoproteomics, and to predict the function of uncharacterized genes.

In 2010, the most "complete" gene interactome produced to date was compiled from about 5.4 million two-gene comparisons to describe "the interaction profiles for ~75% of all genes in the budding yeast", with ~170,000 gene interactions. The genes were grouped based on similar function so as to build a functional map of the cell's processes. Using this method the study was able to predict known gene functions better than any other genome-scale data set as well as adding functional information for genes that hadn't been previously described. From this model genetic interactions can be observed at multiple scales which will assist in the study of concepts such as gene conservation. Some of the observations made from this study are that there were twice as many negative as positive interactions, negative interactions were more informative than positive interactions, and genes with more connections were more likely to result in lethality when disrupted.

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