Background: Molecular interaction networks (MINs) aim to capture the complex relationships between interacting molecules within a biological system. MINs can be constructed from existing knowledge of molecular functional associations, such as protein-protein binding interactions (PPI) or gene co-expression, and these different sources may be combined into a single MIN. A given MIN may be more or less optimal in its representation of the important functional relationships of molecules in a tissue. Objective: The aim of this study was to establish whether a combined MIN derived from different types of functional association could better capture muscle-relevant biology compared to its constituent single-source MINs. Methods: MINs were constructed from functional association databases for both protein-binding and gene co-expression. The networks were then compared based on the capture of muscle-relevant genes and gene ontology (GO) terms, tested in two different ways using established biological network clustering algorithms. The top performing MINs were combined to test whether an optimal MIN for skeletal muscle could be constructed. Results: The STRING PPI network was the best performing single-source MIN among those tested. Combining STRING with interactions from either the MyoMiner or CoXPRESSdb gene co-expression sources resulted in a combined network with improved performance relative to its constituent networks. Conclusion: MINs constructed from multiple types of functional association can better represent the functional relationships of molecules in a given tissue. Such networks may be used to improve the analysis and interpretation of functional genomics data in the study of skeletal muscle and neuromuscular diseases. Networks and clusters described by this study, including the combinations of STRING with MyoMiner or with CoXPRESSdb, are available for download from https://www.sys-myo.com/myominer/download.php.
Bibliographical noteFunding Information:
SM was supported by a studentship from the Department for Employment and Learning Northern Ireland. The work was also supported by the Target-ALS Foundation, and by a programme grant jointly from the European Union Regional Development Fund (ERDF) EU Sustainable Competitiveness Programme for N. Ireland/NI Public Health Agency (HSC R&D) and Ulster University.
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- Skeletal muscle
- functional genomics
- gene co-expression
- molecular interaction networks
- network medicine
- neuromuscular disease
- protein-protein interactions