From Experimental Approaches to Computational Techniques: A Review on the Prediction of Protein-Protein Interactions

Table 2

An overview of large-scale experimental methods applied for the detection of PPIs on an interactome-wide scale. The first column states the name of the experiment followed by a description and a reference.

Technique	Description	Reference
Y2H	The Y2H employs a “two-plasmid” approach in yeast. The yeast protein GAL4 is a transcriptional activator consisting of two domains. The domains must be in close proximity to start the transcription process. The two plasmids are placed into a cell. A physical interaction occurs if the GAL4 binding and activation domains come together if physical interaction occurs, demonstrating that the “bait” and “target” bind [37]. This technique provides evidence of direct physical interactions between proteins.	[33, 38, 39]
MS TAP	Affinity tags are attached to a protein of interest (target), systematic precipitation of bait proteins is performed. Proteins are separated according to their mass to uncover purified protein complexes. Proteins are removed from a gel and analysed by MS techniques [40]. This technique provides evidence of direct physical interactions between proteins.	[34]
Gene coexpression	Gene expression profiles can be obtained from cell cycle experiments and the measurement of gene expression levels when the cell is under different conditions [41]. Gene expression similarity values may be calculated as the Pearson correlation co-efficient between expression levels of two proteins Protein pairs that are coexpressed are more likely to be interacting proteins [35, 42]. This technique provides indirect evidence of interactions between proteins.	[35, 42]
Synthetic lethality	This method involves the deletion or mutation of two genes which are viable alone, but cause lethality when combined in a cell under specific conditions [36, 43]. Synthetic interactions may detect PPIs between gene products, their occurrence in a pathway or participation in a function [40]. This technique provides indirect evidence of interactions between proteins.	[36, 43]