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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 two component proteins from Bradyrhizobium japonicum onto the human composite protein EPXH2. GI numbers are provided. Drawn to scale as in Figure 1.
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bbs072-F2: Mapping of two component proteins from Bradyrhizobium japonicum onto the human composite protein EPXH2. GI numbers are provided. Drawn to scale as in Figure 1.

Mentions: 04 Inspired by such methods, detailed specificity screens have been performed for bifunctional enzymes, such as the human soluble epoxide hydrolase (EPXH2) [33]. While the domains are well delimited as a putative phosphatase (N-terminal) and epoxide hydrolase (C-terminal), their roles have not been understood in detail and were subject to functional analysis for the delineation of their function: human and mouse enzymes are bifunctional, while plant enzymes reportedly lack the phosphatase domain [33]. We note that two bacterial genes from Bradyrhizobium japonicum USDA110 map to the corresponding mammalian composite protein [gene identification number (GI):27376073 and GI:27376225), therefore augmenting the argument of interaction (Figure 2). These interesting discoveries are further strengthened by structure simulation and mechanistic interpretations for catalytic activities of the fused complex [34].Figure 2


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 two component proteins from Bradyrhizobium japonicum onto the human composite protein EPXH2. GI numbers are provided. 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-F2: Mapping of two component proteins from Bradyrhizobium japonicum onto the human composite protein EPXH2. GI numbers are provided. Drawn to scale as in Figure 1.
Mentions: 04 Inspired by such methods, detailed specificity screens have been performed for bifunctional enzymes, such as the human soluble epoxide hydrolase (EPXH2) [33]. While the domains are well delimited as a putative phosphatase (N-terminal) and epoxide hydrolase (C-terminal), their roles have not been understood in detail and were subject to functional analysis for the delineation of their function: human and mouse enzymes are bifunctional, while plant enzymes reportedly lack the phosphatase domain [33]. We note that two bacterial genes from Bradyrhizobium japonicum USDA110 map to the corresponding mammalian composite protein [gene identification number (GI):27376073 and GI:27376225), therefore augmenting the argument of interaction (Figure 2). These interesting discoveries are further strengthened by structure simulation and mechanistic interpretations for catalytic activities of the fused complex [34].Figure 2

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