Mapping the human protein interactome

Abstract

Interactions are the essence of all biomolecules because they cannot fulfill their roles without interacting with other molecules. Hence, mapping the interactions of biomolecules can be useful for understanding their roles and functions. Furthermore, the development of molecular based systems biology requires an understanding of the biomolecular interactions. In recent years, the mapping of protein-protein interactions in different species has been reported, but few reports have focused on the large-scale mapping of protein-protein interactions in human. Here, we review the developments in protein interaction mapping and we discuss issues and strategies for the mapping of the human protein interactome. The latest craze in science is systems biology. Scientists in different scientific fields, however, define and view "systems biology" in different ways. Systems biology, for example, can mean mathematical modeling of a system for accurate predictions of the behavior of the system. It can also mean the systematic application of different highthroughput approaches to gather information on the system and to combine different information spaces for a more comprehensible view of the biology at hand. To date, the best modeling and predictions have been on systems for which good biological information is available [1]. Hence, gathering information on the system is required to develop predictive models. Genomics has been the primary source of large-scale information on systems through genome sequencing, large-scale SNPs analyses, and gene expression studies. KeywordsThe success of genomics has snow-balled into other areas, such as the large-scale data gathering at the protein level (proteomics). One of the achievements of proteomics is the mapping of protein interactions (interactome; the ensemble of the protein interactions related to a proteome or a genome). We have seen a growing number of large-scale studies of the interactome (or part of) for different species including yeast [2][3][4][5][6][7] Should the human protein interactome be mapped?The first question can be easily answered and is reminiscent of early discussions about sequencing the human genome. Many scientists were doubtful that sequencing the human genome would be worth the effort. It is now clear that today's research in human diseases and biological processes benefits from the human genome project. We already have a glimpse of the potential outcomes of mapping the human interactome by looking at the yeast interactome. The importance of mapping the yeast interactome can be measured in different ways; however, the number of references to the original papers by Fields [22] (over 3 000 citations) for interaction mapping by Y2H; and Ho [4] (over 1 300 citations) and Gavin [6] (over 1 400 citations) for protein interaction mapping by mass spectrometry clearly npg Cell Research (2008) 18:716-724.

Streamlined analysis schema for high-throughput identification of endogenous protein complexes

“…Such experiments are limited to moderate size nontoxic proteins and may produce false-positive associations due to the overexpression of bait antigens or the epitope tag itself (12). More recent methodological studies have attempted to address these issues by improving the efficiency of tagging procedures, regulating levels of expression, devising quantitative measures for differentiation of nonspecific interactions, and by increasing experimental reproducibility (13)(14)(15)(16)(17)(18). Still, these attempts cannot resolve a need for studying endogenous protein complexes and for performing large-scale comparative analyses between different cell types.…”

Defining protein interactions that regulate disease progression

“…Several different experimental methods have been developed to identify protein-protein interactions such as coimmunoprecipitation experiments [7] , the BRET (bioluminescence resonance energy transfer) [8] and FRET (fluorescence resonance energy transfer) [9] methods, affinity chromatography [10] and phage display [11] , but the methods that have been most popular in recent years are the yeast two-hybrid system [12] and the protein affinity purification procedure coupled to mass spectrometry (AP-MS) (see [13] for a review and [14] for an example) (refer to Table 1 for a summary of the methods used for studying protein-protein interactions). Co-immunoprecipitation, BRET, FRET, affinity chromatography and phage display approaches have mainly been used to confirm direct, pair-wise interactions between already known partners.…”

Dynamics of Protein Complexes Tracked by Quantitative Proteomics

“…From this list of limitations, it is claimed that one assay may be more efficient to capture one type of protein interaction and vice versa. This might explain, at least partially, the small overlap between protein interactions identified by these techniques, due to how fundamentally different they are (Cusick et al, 2005;Figeys, 2008). This does not necessarily reflect the poor reliability of the reported data, but instead, the poor sensitivity of these approaches, which cannot individually cover the whole interactome network due to the technique limitations described above and a still weak sensitivity of detection (Lemmens et al, 2010).…”