Интерактом: Полный набор молекулярных взаимодействий в клетке.

Complete set of molecular interactions in a biological cell
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. Though 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.

Interactomics is a discipline at the intersection of bioinformatics and biology that deals with studying both the interactions and the consequences of those interactions between and among proteins, and other molecules within a cell. Interactomics thus aims to compare such networks of interactions (i. e., interactomes) between and within species in order to find how the traits of such networks are either preserved or varied. Interactomics is an example of "top down" systems biology, which takes an overhead view of a biosystem or organism. Large sets of genome wide and proteomic data are collected, and correlations between different molecules are inferred. From the data new hypotheses are formulated about feedbacks between these molecules. These hypotheses can then be tested by new experiments.

The study of interactomes is called interactomics. The basic unit of a protein network is the protein–protein interaction (PPI). While there are numerous methods to study PPIs, there are relatively few that have been used on a large scale to map whole interactomes. The yeast two hybrid system (Y2H) is suited to explore the binary interactions among two proteins at a time. Affinity purification and subsequent mass spectrometry is suited to identify a protein complex. Both methods can be used in a high throughput (HTP) fashion. Yeast two hybrid screens allow false positive interactions between proteins that are never expressed in the same time and place; affinity capture mass spectrometry does not have this drawback, and is the current gold standard. Yeast two hybrid data better indicates non specific tendencies towards sticky interactions rather while affinity capture mass spectrometry better indicates functional in vivo protein–protein interactions.

Once an interactome has been created, there are numerous ways to analyze its properties. However, there are two important goals of such analyses. First, scientists try to elucidate the systems properties of interactomes, e. g. the topology of its interactions. Second, studies may focus on individual proteins and their role in the network. Such analyses are mainly carried out using bioinformatics methods and include the following, among many others:

First, the coverage and quality of an interactome has to be evaluated. Interactomes are never complete, given the limitations of experimental methods. For instance, it has been estimated that typical Y2H screens detect only 25% or so of all interactions in an interactome. Other methods filter out false positives calculating the similarity of known annotations of the proteins involved or define a likelihood of interaction using the subcellular localization of these proteins.

[[File:Schziophrenia PPI. jpg|400px|right|thumb | Schizophrenia PPI. In addition, proteins and their interactions change during evolution and thus may have been lost or gained. Nevertheless, numerous interactomes have been predicted, e. g. that of Bacillus licheniformis. Some algorithms use experimental evidence on structural complexes, the atomic details of binding interfaces and produce detailed atomic models of protein–protein complexes as well as other protein–molecule interactions. Other algorithms use only sequence information, thereby creating unbiased complete networks of interaction with many mistakes. Some methods use machine learning to distinguish how interacting protein pairs differ from non interacting protein pairs in terms of pairwise features such as cellular colocalization, gene co expression, how closely located on a DNA are the genes that encode the two proteins, and so on. Random Forest has been found to be most effective machine learning method for protein interaction prediction. Such methods have been applied for discovering protein interactions on human interactome, specifically the interactome of Membrane proteins

Protein interaction networks have been used to predict the function of proteins of unknown functions. This is usually based on the assumption that uncharacterized proteins have similar functions as their interacting proteins (guilt by association). For example, YbeB, a protein of unknown function was found to interact with ribosomal proteins and later shown to be involved in bacterial and eukaryotic (but not archaeal) translation. Although such predictions may be based on single interactions, usually several interactions are found. Thus, the whole network of interactions can be used to predict protein functions, given that certain functions are usually enriched among the interactors.

The topology of an interactome makes certain predictions how a network reacts to the perturbation (e. g. removal) of nodes (proteins) or edges (interactions). Such perturbations can be caused by mutations of genes, and thus their proteins, and a network reaction can manifest as a disease. A network analysis can identify drug targets and biomarkers of diseases.

Interaction networks can be analyzed using the tools of graph theory. Network properties include the degree distribution, clustering coefficients, betweenness centrality, and many others. The distribution of properties among the proteins of an interactome has revealed that the interactome networks often have scale free topology where functional modules within a network indicate specialized subnetworks. Such modules can be functional, as in a signaling pathway, or structural, as in a protein complex. In fact, it is a formidable task to identify protein complexes in an interactome, given that a network on its own does not directly reveal the presence of a stable complex.

Protinfo PPC predicts the atomic 3D structure of protein protein complexes. IBIS (server) reports, predicts and integrates multiple types of conserved interactions for proteins.