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Experimental evidence validating the computational inference of functional associations from gene fusion events: a critical survey.

Promponas VJ, Ouzounis CA, Iliopoulos I - Brief. Bioinformatics (2012)

Bottom Line: Furthermore, this view has raised the real possibility to detect functional associations of genes and their corresponding proteins for any entire genome sequence.In this critical survey, we provide a comprehensive overview of 30 most prominent examples of single pairwise protein interaction cases in small-scale studies, where protein interactions have either been detected by gene fusion or yielded additional, corroborating evidence from biochemical observations.Our conclusion is that with the derivation of a validated gold-standard corpus and better data integration with big experiments, gene fusion detection can truly become a valuable tool for large-scale experimental biology.

View Article: PubMed Central - PubMed

Affiliation: Institute of Agrobiotechnology, Centre for Research & Technology Hellas (CERTH), 57001 Thessaloniki, Greece. ouzounis@certh.gr.

ABSTRACT
More than a decade ago, a number of methods were proposed for the inference of protein interactions, using whole-genome information from gene clusters, gene fusions and phylogenetic profiles. This structural and evolutionary view of entire genomes has provided a valuable approach for the functional characterization of proteins, especially those without sequence similarity to proteins of known function. Furthermore, this view has raised the real possibility to detect functional associations of genes and their corresponding proteins for any entire genome sequence. Yet, despite these exciting developments, there have been relatively few cases of real use of these methods outside the computational biology field, as reflected from citation analysis. These methods have the potential to be used in high-throughput experimental settings in functional genomics and proteomics to validate results with very high accuracy and good coverage. In this critical survey, we provide a comprehensive overview of 30 most prominent examples of single pairwise protein interaction cases in small-scale studies, where protein interactions have either been detected by gene fusion or yielded additional, corroborating evidence from biochemical observations. Our conclusion is that with the derivation of a validated gold-standard corpus and better data integration with big experiments, gene fusion detection can truly become a valuable tool for large-scale experimental biology.

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A pictorial representation of the gene fusion detection/association inference process. A composite protein (bottom) with two domains exhibits sequence similarities to two component homologs [Component 1 (green) and Component 2 (blue) with 360 and 450 amino acid residues (aa), respectively—not shown]. The total length of the fictitious protein sequence is 1200 residues, drawn to scale—unit shown (120 residues). Networks of associations, with nodes (grey) corresponding to genes/proteins and links (purple) depicting pairwise interactions, can thus include the corresponding (color-coded) component proteins identified by their similarity to composite proteins and inferred to be functionally linked.
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bbs072-F1: A pictorial representation of the gene fusion detection/association inference process. A composite protein (bottom) with two domains exhibits sequence similarities to two component homologs [Component 1 (green) and Component 2 (blue) with 360 and 450 amino acid residues (aa), respectively—not shown]. The total length of the fictitious protein sequence is 1200 residues, drawn to scale—unit shown (120 residues). Networks of associations, with nodes (grey) corresponding to genes/proteins and links (purple) depicting pairwise interactions, can thus include the corresponding (color-coded) component proteins identified by their similarity to composite proteins and inferred to be functionally linked.

Mentions: Much followed since, and a number of high-profile reports announced the arrival of new methods such as gene clusters [6], gene fusion [8] and phylogenetic profiles [3]. In particular, gene fusion analysis has provided a basis for the detection of protein interactions in whole genomes [8, 9]. Compared with the other genome-aware methods above, it was shown to be far more reliable with respect to precision (i.e. high-quality predictions with few false positives) [10], albeit with lower coverage as expected. This method is based on the observation of two separate genes in one genome found to be fused in another genome (Figure 1).Figure 1


Experimental evidence validating the computational inference of functional associations from gene fusion events: a critical survey.

Promponas VJ, Ouzounis CA, Iliopoulos I - Brief. Bioinformatics (2012)

A pictorial representation of the gene fusion detection/association inference process. A composite protein (bottom) with two domains exhibits sequence similarities to two component homologs [Component 1 (green) and Component 2 (blue) with 360 and 450 amino acid residues (aa), respectively—not shown]. The total length of the fictitious protein sequence is 1200 residues, drawn to scale—unit shown (120 residues). Networks of associations, with nodes (grey) corresponding to genes/proteins and links (purple) depicting pairwise interactions, can thus include the corresponding (color-coded) component proteins identified by their similarity to composite proteins and inferred to be functionally linked.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4017328&req=5

bbs072-F1: A pictorial representation of the gene fusion detection/association inference process. A composite protein (bottom) with two domains exhibits sequence similarities to two component homologs [Component 1 (green) and Component 2 (blue) with 360 and 450 amino acid residues (aa), respectively—not shown]. The total length of the fictitious protein sequence is 1200 residues, drawn to scale—unit shown (120 residues). Networks of associations, with nodes (grey) corresponding to genes/proteins and links (purple) depicting pairwise interactions, can thus include the corresponding (color-coded) component proteins identified by their similarity to composite proteins and inferred to be functionally linked.
Mentions: Much followed since, and a number of high-profile reports announced the arrival of new methods such as gene clusters [6], gene fusion [8] and phylogenetic profiles [3]. In particular, gene fusion analysis has provided a basis for the detection of protein interactions in whole genomes [8, 9]. Compared with the other genome-aware methods above, it was shown to be far more reliable with respect to precision (i.e. high-quality predictions with few false positives) [10], albeit with lower coverage as expected. This method is based on the observation of two separate genes in one genome found to be fused in another genome (Figure 1).Figure 1

Bottom Line: Furthermore, this view has raised the real possibility to detect functional associations of genes and their corresponding proteins for any entire genome sequence.In this critical survey, we provide a comprehensive overview of 30 most prominent examples of single pairwise protein interaction cases in small-scale studies, where protein interactions have either been detected by gene fusion or yielded additional, corroborating evidence from biochemical observations.Our conclusion is that with the derivation of a validated gold-standard corpus and better data integration with big experiments, gene fusion detection can truly become a valuable tool for large-scale experimental biology.

View Article: PubMed Central - PubMed

Affiliation: Institute of Agrobiotechnology, Centre for Research & Technology Hellas (CERTH), 57001 Thessaloniki, Greece. ouzounis@certh.gr.

ABSTRACT
More than a decade ago, a number of methods were proposed for the inference of protein interactions, using whole-genome information from gene clusters, gene fusions and phylogenetic profiles. This structural and evolutionary view of entire genomes has provided a valuable approach for the functional characterization of proteins, especially those without sequence similarity to proteins of known function. Furthermore, this view has raised the real possibility to detect functional associations of genes and their corresponding proteins for any entire genome sequence. Yet, despite these exciting developments, there have been relatively few cases of real use of these methods outside the computational biology field, as reflected from citation analysis. These methods have the potential to be used in high-throughput experimental settings in functional genomics and proteomics to validate results with very high accuracy and good coverage. In this critical survey, we provide a comprehensive overview of 30 most prominent examples of single pairwise protein interaction cases in small-scale studies, where protein interactions have either been detected by gene fusion or yielded additional, corroborating evidence from biochemical observations. Our conclusion is that with the derivation of a validated gold-standard corpus and better data integration with big experiments, gene fusion detection can truly become a valuable tool for large-scale experimental biology.

Show MeSH