Interactome

Interactome

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Encyclopedia
Interactome is defined as the whole set of molecular interactions in cells. It is usually displayed as a directed graph
Directed graph
A directed graph or digraph is a pair G= of:* a set V, whose elements are called vertices or nodes,...

. Molecular interactions can occur between molecules belonging to different biochemical families (proteins, nucleic acids, lipids, carbohydrates, etc.) and also within a given family. When spoken in terms of proteomics
Proteomics
Proteomics is the large-scale study of proteins, particularly their structures and functions. Proteins are vital parts of living organisms, as they are the main components of the physiological metabolic pathways of cells. The term "proteomics" was first coined in 1997 to make an analogy with...

, interactome refers to protein–protein interaction network (PPI), or protein interaction network (PIN). Another extensively studied type of interactome is the protein–DNA interactome (network formed by transcription factors (and DNA or chromatin regulatory proteins) and their target genes. The word "interactome" was originally coined in 1999 by a group of French scientists headed by Bernard Jacq (see Nucleic acids research 27(1):89-94; PubMed ID: 9847149).

It has been suggested that the size of an organism's interactome correlates better than genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....

 size with the biological complexity of the organism (Stumpf, et al., 2008). Although protein–protein interaction maps containing several thousands of binary interactions are now available for several organisms, none of them is presently complete and the size of interactomes is still a matter of debate. In 2010, the most "complete" gene interactome produced to date was compiled from 54 million two-gene comparisons to describe "the interaction profiles for ~75% of all genes in the Budding yeast," with 170,000 gene interactions.

Although extremely important and useful, the interactome is still being developed and is not complete . There are various factors that have a role in protein interactions that have yet to be incorporated in the interactome. Many have termed the interactome as a whole as being fuzzy. The binding strength of the various proteins, microenvironmental factors, sensitivity to various procedures, and the physiological state of the cell all affect protein–protein interactions, yet are not accounted for in the interactome. Although the interactome is useful in some ways, it must be analyzed knowing that these factors exist and can affect the protein interactions.

Methods of mapping the interactome


The study of the interactome is called interactomics
Interactomics
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. The network of all such interactions is called the Interactome...

. The basic unit of protein network is protein–protein interaction (PPI). Because the interactome considers the whole organism, there is a need to collect a massive amount of information.

Experimental methods have been devised to determine PPI, such as affinity purification and yeast two hybrid
Two-hybrid screening
Two-hybrid screening is a molecular biology technique used to discover protein–protein interactions and protein–DNA interactions by testing for physical interactions between two proteins or a single protein and a DNA molecule, respectively.The premise behind the test is the activation of...

 (Y2H). The former is suited to identify a protein complex, while the latter is suited to explore the binary interactions in mass quantities. The former is considered as a low-throughput method (LTP), while the latter is considered as high-throughput method (HTP).

Using the experimental data as a starting point, the concept of homology transfer has been used to develop algorithms to map the interactome,
including ones that produce detailed atomic models of protein protein complexes
as well as other protein–molecule interactions.

There have been several efforts to map the eukaryotic interactome through HTP methods. , yeast, fly, worm, and human HTP maps have been created. Recently, pathogen-host interactome (Hepatitis C Virus/Human (2008), Epstein Barr virus/Human (2008), Influenza virus/Human (2009)) was also delineated through HTP to identify essential molecular components for pathoghens but also for the host to recognize pathogens and trigger efficient innate immune response.

Using the interactome


Researchers have begun to use preliminary versions of the interactome to gain understanding about the biology and function of the molecules within them. For example, protein interaction networks have been used to produce improved protein functional annotations (or nannotations) for proteins with unknown functions.

Interactome web servers

  • Protinfo PPC predicts the atomic 3D structure of protein protein complexes.

Interactome databases

  • APID: Agile Protein Interaction DataAnalyzer – an interactive bioinformatic web-tool that integrates and unifies main known experimentally validated protein–protein interactions (Prieto and De Las Rivas, 2006).
  • BioGRID database
  • Bioverse database
  • ConsensusPathDB
    ConsensusPathDB
    The ConsensusPathDB is a molecular functional interaction database, integrating information on protein interactions, signaling, metabolism and gene regulation in humans. ConsensusPathDB includes functional interactions from 12 databases...

     includes functional interactions from 12 other databases
  • Database of interacting proteins
    Database of Interacting Proteins
    The catalogs experimentally determined interactions between proteins. It combines information from a variety of sources to create a single, consistent set of protein–protein interactions...

     (DIP) (Xenarios et al. 2000).
  • MIPS database
  • PSIMAP database — the first protein structural interactome DB


External links