gep2pep-package: gep2pep: creation and analysis of Pathway Expression Profiles
In gep2pep: Creation and Analysis of Pathway Expression Profiles (PEPs)

Description Details Author(s) References

Pathway Expression Profiles (PEPs) are based on the expression of pathways (or generic gene sets) belonging to a collection, as opposed to individual genes. gep2pep supports the conversion of gene expression profiles (GEPs) to PEPs and performs enrichment analysis of both pathways and conditions.

gep2pep creates a local repository of gene sets, which can also be imported from the MSigDB [1] database. The local repository is in the repo format. When a GEP, defined as a ranked list of genes, is passed to buildPEPs, the stored database of pathways is used to convert the GEP to a PEP and permanently store the latter.

One type of analysis that can be performed on PEPs and that is directly supported by gep2pep is the Drug-Set Enrichment Analysis (DSEA [2]). It finds pathways that are consistently dysregulated by a set of drugs, as opposed to a background of other drugs. Of course PEPs may refer to non-pharmacological conditions (genetic perturbations, disease states, cell types, etc.) for analogous analyses. See CondSEA function.

A complementary approach is that of finding conditions that consistently dysregulate a set of pathways. This is the pathway-based version of the Gene Set Enrichment Analysis (GSEA). As an application example, this approach can be used to find drugs mimicking the dysregulation of a gene by looking for drugs dysregulating pathways involving the gene (this has been published as the gene2drug tool [3]). See PathSEA.

Both DSEA and gene2drug analyses can be performed using preprocessed data from http://dsea.tigem.it/downloads.php. The data include Connectivity Map [4] GEPs (drug-induced gene expression profiles) converted to PEPs in the form of a gep2pep repository.

Naming conventions:

pathway: any set of gene identifiers (not necessarily representing a molecular pathway).
pathway collection: a set of pathways.
pathway database: a set of pathway collections, like the MSigDB.
Gene Expression Profile (GEP): a named vector where names are gene identifiers of the same type as those in the pathway database and elements are ranks ranging from 1 to the number of genes.
Pathway Expression Profile (PEP): a ranked list of pathways, as converted from a GEP according to a pathway collection.
condition: any transcriptomic-modelled biological state (drug treatment, gene knock-out, disease state, cell type, etc.) characterized by an induced GEP and therefore a PEP.
gep2pep repository: a pathway database and possibly a related database of PEPs as created by the gep2pep package. It is implemented in repo format.

Francesco Napolitano franapoli@gmail.com

[1] Subramanian A. et al. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. PNAS 102, 15545-15550 (2005).

[2] Napolitano F. et al, Drug-set enrichment analysis: a novel tool to investigate drug mode of action. Bioinformatics 32, 235-241 (2016).

[3] Napolitano, F. et al. gene2drug: a computational tool for pathway-based rational drug repositioning. Bioinformatics (2017). https://doi.org/10.1093/bioinformatics/btx800

[4] Lamb, J. et al. The Connectivity Map: Using Gene-Expression Signatures to Connect Small Molecules, Genes, and Disease. Science 313, 1929-1935 (2006).

gep2pep documentation built on Nov. 8, 2020, 5:59 p.m.