Background: Gene-set analysis (GSA) has been commonly used to identify significantly altered pathways or functions from omics data. However, GSA often yields a long list of gene-sets, necessitating efficient post-processing for improved interpretation. Existing methods cluster the gene-sets based on the extent of their overlap to summarize the GSA results without considering interactions between gene-sets.
Results: Here, we presented a novel network-weighted gene-set clustering that incorporates both the gene-set overlap and protein-protein interaction (PPI) networks. Three examples were demonstrated for microarray gene expression, GWAS summary, and RNA-sequencing data to which different GSA methods were applied. These examples as well as a global analysis show that the proposed method increases PPI densities and functional relevance of the resulting clusters. Additionally, distinct properties of gene-set distance measures were compared. The methods are implemented as an R/Shiny package GScluster that provides gene-set clustering and diverse functions for visualization of gene-sets and PPI networks.
Conclusions: Network-weighted gene-set clustering provides functionally more relevant gene-set clusters and related network analysis.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507172 | PMC |
| http://dx.doi.org/10.1186/s12864-019-5738-6 | DOI Listing |
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