BNrich: A Bayesian network approach to the pathway enrichment analysis [article]

Samaneh Maleknia, Ali Sharifi-Zarchi, Vahid Rezaei Tabar, Mohsen Namazi, Kaveh Kavousi
2020 bioRxiv   pre-print
Motivation: One of the most popular techniques in biological studies for analyzing high throughput data is pathway enrichment analysis (PEA). Many researchers apply the existing methods without considering the topology of pathways or at least they have overlooked a significant part of the structure, which may reduce the accuracy and generalizability of the results. Developing a new approach while considering gene expression data and topological features like causal relations regarding edge
more » ... tions will help the investigators to achieve more accurate results. Results: We proposed a new pathway enrichment analysis based on Bayesian network (BNrich) as an approach in PEA. To this end, the cycles were eliminated in 187 KEGG human signaling pathways concerning intuitive biological rules and the Bayesian network structures were constructed. The constructed networks were simplified by the Least Absolute Shrinkage Selector Operator (LASSO), and their parameters were estimated using the gene expression data. We finally prioritize the impacted pathways by Fisher's Exact Test on significant parameters. Our method integrates both edge and node related parameters to enrich modules in the affected signaling pathway network. In order to evaluate the proposed method, consistency, discrimination and false positive rate criteria were calculated, and the results are compared to well-known enrichment methods such as signaling pathway impact analysis (SPIA), bi-level meta-analysis (BLMA) and topology-based pathway enrichment analysis (TPEA). Availability: The R package is available on GitHub.
doi:10.1101/2020.01.13.905448 fatcat:rii3gpan2vczdgjo3ct42pxkj4