This further supports the idea that multiple pathway analysis is required, as differences are likely to be subtle and occur at multiple points across several processes [ 3, 26].
To provide a basis for incisive analysis of those complexities and ambiguities and to guide development of new autophagy-targeted treatments for cancer, we have compiled a comprehensive, curated inventory of autophagy modulators by integrating information from published siRNA screens, multiple pathway analysis algorithms, and extensive, manually curated text-mining of the literature.
To assess the presence or absence of a metabolic pathway and to decrease the likelihood of being misled by the many enzymes that are shared among multiple pathways, the analysis was emphasized on the presence of enzymes that are unique to a pathway.
If the complexity of a compartmentalized network creates an unacceptable computational burden, the nested analysis approach permits greater scalability at the cost of more user intervention through multiple rounds of pathway analysis.
The differentially expressed transcripts are annotated in multiple ways: Ingenuity Pathway Analysis Tool (IPA; Redwood City, CA), hypergeometric enrichment of gene ontology (GO) terms, KEGG pathways (using Bioconductor GOstats package) and the gene sets from MSigDB (Molecular Signatures Database, http://www.broadinstitute.org/gsea/msigdb/index.jsp).jsp
When we applied a Benjamini Hochberg correction for multiple testing to the pathway analysis, there were 74 pathways that were significant (p < 0.05).
Pathway analysis revealed multiple pathways including Jak-STAT, TGF-beta, PI3K-Akt and MAPK signaling pathway that are correlated to colorectal cancer.
Metacore pathway analysis predicted multiple targets of miR-206, including KLF4, which was further supported by sequence complementarity alignment.
Finally, an unbiased pathway analysis revealed multiple rare, but mutually exclusive, alterations linked to loss of activity of co-repressor complexes N-Cor and SMRT.
In April 2014, we added a new experimental feature for performing integrated pathway analysis for multiple genomic data types by adapting a factor graph based approach called "PARADIGM" into ReactomeFIViz.
Pathway analysis indicated that multiple pathways associated with transcriptional regulation and supported by multiple independent databases, e.g. GOTERM, BIOCARTA, OMIM disease, etc., were enriched within the shared set of genes that were down-regulated in children with autism and children of older fathers (figure 4c).
