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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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Mapping of the complex domain structure for IcmF in the actinobacterium N. farcinica IFM 10152, GI:54023003, length 1071 residues (aa); orange: cofactor-binding site; green: MCM; blue: ICM—see text for details. Drawn to scale as in Figure 1.
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bbs072-F3: Mapping of the complex domain structure for IcmF in the actinobacterium N. farcinica IFM 10152, GI:54023003, length 1071 residues (aa); orange: cofactor-binding site; green: MCM; blue: ICM—see text for details. Drawn to scale as in Figure 1.

Mentions: 15 Furthermore, in parallel work this particular composite case has been identified as a fusion of isobutyryl-CoA mutase (ICM) and named appropriately as IcmF [54], in Nocardia farcinica for instance (GI:54023003) (Figure 3, suggested domain structure). This is one of the most challenging examples of substrate and cofactor specificity that has not yet been fully elucidated.Figure 3


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)

Mapping of the complex domain structure for IcmF in the actinobacterium N. farcinica IFM 10152, GI:54023003, length 1071 residues (aa); orange: cofactor-binding site; green: MCM; blue: ICM—see text for details. Drawn to scale as in Figure 1.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

bbs072-F3: Mapping of the complex domain structure for IcmF in the actinobacterium N. farcinica IFM 10152, GI:54023003, length 1071 residues (aa); orange: cofactor-binding site; green: MCM; blue: ICM—see text for details. Drawn to scale as in Figure 1.
Mentions: 15 Furthermore, in parallel work this particular composite case has been identified as a fusion of isobutyryl-CoA mutase (ICM) and named appropriately as IcmF [54], in Nocardia farcinica for instance (GI:54023003) (Figure 3, suggested domain structure). This is one of the most challenging examples of substrate and cofactor specificity that has not yet been fully elucidated.Figure 3

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