Fast Gene Set Enrichment Analysis (FGSEA) of transcriptomics and proteomics differential analysis results using Gene Ontology terms from the Molecular Signatures Database (MSigDB v7.5.1).

TRNSCRPT_FGSEA # transcriptomics
PROT_FGSEA     # proteomics

Format

A named list of 3 data.frame objects:

"trained_vs_SED"

All trained timepoints compared to their sex-matched sedentary control group. Example: F_1W - F_SED. Total of 8 contrasts.

"MvF_SED"

Sedentary males compared to sedentary females. Only 1 contrast.

"MvF_exercise_response"

Comparisons of the male and female training responses. Example: (M_8W - M_SED) - (F_8W - F_SED). Total of 4 contrasts.

Each data.frame contains the following 12 variables:

pathway

character; Gene Ontology pathway identifier.

gs_subcat

character; GO:BF (Biological Processes), GO:MF (Molecular Functions), or GO:CC (Cellular Components). See http://geneontology.org/docs/ontology-documentation/

gs_description

character; Gene Ontology set description. See update_GO_names for details.

pval

numeric; enrichment p-value.

padj

numeric; BH-adjusted p-value. P-values are adjusted across all contrasts within each ontology (GO:BP, GO:CC, GO:MF).

log2err

numeric; the expected error for the standard deviation of the p-value logarithm.

ES

numeric; gene set enrichment score.

NES

numeric; normalized enrichment score. Accounts for differences in gene set size. Calculated as the quotient of the ES to the absolute mean of the permutation enrichment scores that have the same sign as the ES. See https://doi.org/10.1101/060012 for details. Values in [-1, 1] are not interesting.

size

integer; number of genes in each pathway after it has been filtered to those that were present in the differential analysis results.

contrast

character; the comparison being made.

leadingEdge

list; the Entrez gene IDs that drive the enrichment. If the set has a negative ES, the genes are arranged from most to least negative; otherwise, they are arranged from most to least positive. See http://software.broadinstitute.org/gsea/doc/GSEAUserGuideTEXT.htm#_Running_a_Leading.

leadingEdge_genes

list; the leadingEdge after mapping Entrez genes to more human-readable gene symbols. Any genes that could not be mapped were discarded, so lengths(leadingEdge_genes) may not match lengths(leadingEdge).

References

Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., Harris, M. A., Hill, D. P., Issel-Tarver, L., Kasarskis, A., Lewis, S., Matese, J. C., Richardson, J. E., Ringwald, M., Rubin, G. M., & Sherlock, G. (2000). Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nature genetics, 25(1), 25–29. https://doi.org/10.1038/75556

Dolgalev, I. msigdbr: MSigDB Gene Sets for Multiple Organisms in a Tidy Data Format. R package version 7.5.1, https:://igordot.github.io/msigdbr

Gene Ontology Consortium (2021). The Gene Ontology resource: enriching a GOld mine. Nucleic acids research, 49(D1), D325–D334. https://doi.org/10.1093/nar/gkaa1113

Korotkevich, G., Sukhov, V., Budin, N., Shpak, B., Artyomov, M. N., & Sergushichev, A. (2021). Fast gene set enrichment analysis. BioRxiv. https://doi.org/10.1101/060012

Liberzon, A., Birger, C., Thorvaldsdóttir, H., Ghandi, M., Mesirov, J. P., & Tamayo, P. (2015). The Molecular Signatures Database (MSigDB) hallmark gene set collection. Cell systems, 1(6), 417–425. https://doi.org/10.1016/j.cels.2015.12.004

Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., & Mesirov, J. P. (2005). Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proceedings of the National Academy of Sciences of the United States of America, 102(43), 15545–15550. https://doi.org/10.1073/pnas.0506580102