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Published on: July 14, 2015
Relationship between insertion/deletion (indel) frequency of proteins and essentiality
Simon K Chan1, Michael Hsing, Fereydoun Hormozdiari
1CIHR/MSFHR Strategic Training Program in Bioinformatics, Canada's Michael Smith Genome Sciences Centre, Vancouver, BC, Canada. sichan@bcgsc.ca <sichan@bcgsc.ca>
BMC Bioinformatics
|June 30, 2007
Summary
Essential proteins in pathogens show higher frequencies of insertions/deletions (indels) compared to non-essential proteins. These indels may play a role in protein interactions and offer new avenues for drug design.
Area of Science:
- Bioinformatics
- Structural Biology
- Drug Discovery
Background:
- Previous studies identified sizable insertions/deletions (indels) in essential pathogenic proteins compared to human proteins.
- These indels create spatial differences, enabling selective targeting of pathogen proteins.
- This led to the development of selective antibodies and compounds against pathogen proteins.
Purpose of the Study:
- To investigate if indels are more prevalent in essential proteins than non-essential proteins.
- To explore the potential of indels as targets for selective drug development.
Main Methods:
- Analysis of protein essentiality data from Bacillus subtilis, Escherichia coli, and Saccharomyces cerevisiae.
- Statistical analysis (t-tests) to compare indel frequencies in essential vs. non-essential proteins.
- Modeling indel abundance using Weibull distribution and evaluating discrimination power with ROC curves.
- Analysis of protein interaction data and network properties (betweenness centrality) in Saccharomyces cerevisiae.
Main Results:
- Essential proteins exhibited significantly higher mean indel frequencies than non-essential proteins across the three species.
- Indel abundance followed a Weibull distribution but indel frequency alone was insufficient for accurate discrimination.
- Indel-bearing proteins in S. cerevisiae were more interactive and central in protein interaction networks.
Conclusions:
- Indels are non-randomly distributed, favoring essential and highly connected proteins.
- Insertions/deletions likely influence protein-protein interactions and their regulation.
- Findings support the utility of indels in bioinformatics and cheminformatics for novel drug design.
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