PathNet: Enrichment and contextual analysis of KEGG pathways
In PathNet: An R package for pathway analysis using topological information

Description Usage Arguments Details Value References Examples

View source: R/PathNet.R

Pathway analysis using Network information (PathNet) algorithm, described in Dutta et al., is implemented in this package. PathNet uses topological information present in pathways and differential expression levels of genes (obtained from microarray experiment) to identify pathways that are 1) significantly enriched and 2) contextually associated with each other. In enrichment analysis, PathNet considers both the differential expression of genes and their pathway neighbors to strengthen the evidence that a pathway is implicated in the biological conditions tested for in the experiment. In addition, PathNet also identifies contextual association between pathway pairs based on connectivity of differentially expressed genes between two pathways.

PathNet(Enrichment_Analysis = TRUE, Contextual_Analysis = FALSE,
               DirectEvidence_info, Column_DirectEvidence = 7, 
               Adjacency, pathway = pathway, n_perm = 2000,
               threshold = 0.05, use_sig_pathways  = FALSE)

`Enrichment_Analysis`	If set to TRUE, enrichment analysis will be carried out
`Contextual_Analysis`	If set to TRUE, contextual analysis will be carried out
`DirectEvidence_info`	Data containing direct evidence information. The negative log10 transformed p-value of the significance of association is used as direct evidence.
`Column_DirectEvidence`	Column of the data matrix to be used
`Adjacency`	Adjacency matrix
`pathway`	Pathway data
`n_perm`	Number of permutations
`threshold`	Threshold of significance
`use_sig_pathways`	A logical variable whether only significance pathways will be used for contextual analysis. If this is TRUE then the Enrichment_Analysis parameter must also be set to TRUE.

See cited document for more details

The PathNet functions returns a list of values reflecting the results of performing pathway enrichment and/or contextual analysis. The items returned in the list are:

`enrichment_results`	Significance levels of enrichment for each pathway from PathNet and the hypergeometric test. These levels are in a dataframe which contains gene ID, direct, indirect, and combined evidence levels of genes present in the microarray data. Indirect evidences are calculated only for the genes that are present in the KEGG pathway and have at least one edge. For the rest of the genes, indirect evidences are “NA” and the combined evidences are replaced by the direct evidences.
`enrichment_combined_evidence`	A data frame containing gene ID, direct, indirect, and combined evidence levels of genes present in the microarray data. The results are sorted in increasing order based on the p_PathNet_FWER value. Results include pathway name (Name), number of genes of the pathway present in the microarray data (No_of_Genes), number of genes significant from direct evidence (Sig_Direct), number of genes significant from combined evidence (Sig_Combi), significance of enrichment from hypergeometric test (p_Hyper), family wise error rate correction of p_Hyper (p_Hyper_FWER), significance of enrichment from PathNet (p_PathNet), and family wise error rate correction of p_PathNet (p_PathNet_FWER).
`conn_p_value`	Contains the results of the contextual association in the form of a square matrix, where the number of rows (and columns) is equal to the number of pathways. The element at the ith row and jth column denotes the significance of contextual association of pathway i with pathway j.
`pathway_overlap`	The statistical significance of the overlapping genes between all pathway pairs in the form of a square matrix. This information is only based on the KEGG database and is not dependent on gene expression data. The hypergeometric test is used to estimate if the observed overlap is statistically significant. If use_sig_pathways parameter is set to TRUE, both contextual association and overlap analysis results are sorted in decreasing order of pathway enrichment. Otherwise, the pathways appear in alphabetical order of pathway names.

PathNet: A tool for pathway analysis using topological information. Dutta B, Wallqvist A, and Reifman J. Source Code for Biology and Medicine 2012 Sep 24;7(1):10.

library(PathNetData)
data(brain_regions)
data(pathway)
data(A)

# Perform an example enrichment analysis using  a
# subset of data and a small number of permutations
# for demonstration purposes.
results <- PathNet(Enrichment_Analysis = TRUE, Contextual_Analysis = FALSE, 
        DirectEvidence_info = brain_regions[1:100,], Column_DirectEvidence = 7,
        Adjacency = A , pathway = pathway, n_perm = 10, threshold = 0.05,
        use_sig_pathways  = FALSE)
        
# display part of results
head(results$enrichment_results)
head(results$enrichment_combined_evidence)

Number of genes present in the DirectEvidence File:
100
Starting enrichment analysis
Processing  130 pathways
Completed enrichment analysis of ABC transporters pathway
Completed enrichment analysis of Acute myeloid leukemia pathway
Completed enrichment analysis of Adherens junction pathway
Completed enrichment analysis of Adipocytokine signaling pathway pathway
Completed enrichment analysis of Aldosterone-regulated sodium reabsorption pathway
Completed enrichment analysis of Allograft rejection pathway
Completed enrichment analysis of Alzheimers disease pathway
Completed enrichment analysis of Amoebiasis pathway
Completed enrichment analysis of Amyotrophic lateral sclerosis (ALS) pathway
Completed enrichment analysis of Antigen processing and presentation pathway
Completed enrichment analysis of Apoptosis pathway
Completed enrichment analysis of Arrhythmogenic right ventricular cardiomyopathy (ARVC) pathway
Completed enrichment analysis of Asthma pathway
Completed enrichment analysis of Autoimmune thyroid disease pathway
Completed enrichment analysis of Axon guidance pathway
Completed enrichment analysis of B cell receptor signaling pathway pathway
Completed enrichment analysis of Bacterial invasion of epithelial cells pathway
Completed enrichment analysis of Basal cell carcinoma pathway
Completed enrichment analysis of Basal transcription factors pathway
Completed enrichment analysis of Base excision repair pathway
Completed enrichment analysis of Bladder cancer pathway
Completed enrichment analysis of Calcium signaling pathway pathway
Completed enrichment analysis of Carbohydrate digestion and absorption pathway
Completed enrichment analysis of Cardiac muscle contraction pathway
Completed enrichment analysis of Cell adhesion molecules (CAMs) pathway
Completed enrichment analysis of Cell cycle pathway
Completed enrichment analysis of Chagas disease pathway
Completed enrichment analysis of Chemokine signaling pathway pathway
Completed enrichment analysis of Chronic myeloid leukemia pathway
Completed enrichment analysis of Circadian rhythm - mammal pathway
Completed enrichment analysis of Collecting duct acid secretion pathway
Completed enrichment analysis of Colorectal cancer pathway
Completed enrichment analysis of Complement and coagulation cascades pathway
Completed enrichment analysis of Cytokine-cytokine receptor interaction pathway
Completed enrichment analysis of Cytosolic DNA-sensing pathway pathway
Completed enrichment analysis of Dilated cardiomyopathy pathway
Completed enrichment analysis of DNA replication pathway
Completed enrichment analysis of Dorso-ventral axis formation pathway
Completed enrichment analysis of ECM-receptor interaction pathway
Completed enrichment analysis of Endocytosis pathway
Completed enrichment analysis of Endometrial cancer pathway
Completed enrichment analysis of Epithelial cell signaling in Helicobacter pylori infection pathway
Completed enrichment analysis of ErbB signaling pathway pathway
Completed enrichment analysis of Fc epsilon RI signaling pathway pathway
Completed enrichment analysis of Fc gamma R-mediated phagocytosis pathway
Completed enrichment analysis of Focal adhesion pathway
Completed enrichment analysis of Gap junction pathway
Completed enrichment analysis of Gastric acid secretion pathway
Completed enrichment analysis of Glioma pathway
Completed enrichment analysis of GnRH signaling pathway pathway
Completed enrichment analysis of Graft-versus-host disease pathway
Completed enrichment analysis of Hedgehog signaling pathway pathway
Completed enrichment analysis of Hematopoietic cell lineage pathway
Completed enrichment analysis of Homologous recombination pathway
Completed enrichment analysis of Huntingtons disease pathway
Completed enrichment analysis of Hypertrophic cardiomyopathy (HCM) pathway
Completed enrichment analysis of Insulin signaling pathway pathway
Completed enrichment analysis of Intestinal immune network for IgA production pathway
Completed enrichment analysis of Jak-STAT signaling pathway pathway
Completed enrichment analysis of Leishmaniasis pathway
Completed enrichment analysis of Leukocyte transendothelial migration pathway
Completed enrichment analysis of Long-term depression pathway
Completed enrichment analysis of Long-term potentiation pathway
Completed enrichment analysis of Lysosome pathway
Completed enrichment analysis of Malaria pathway
Completed enrichment analysis of MAPK signaling pathway pathway
Completed enrichment analysis of Maturity onset diabetes of the young pathway
Completed enrichment analysis of Melanogenesis pathway
Completed enrichment analysis of Melanoma pathway
Completed enrichment analysis of Mismatch repair pathway
Completed enrichment analysis of mTOR signaling pathway pathway
Completed enrichment analysis of Natural killer cell mediated cytotoxicity pathway
Completed enrichment analysis of Neuroactive ligand-receptor interaction pathway
Completed enrichment analysis of Neurotrophin signaling pathway pathway
Completed enrichment analysis of NOD-like receptor signaling pathway pathway
Completed enrichment analysis of Non-homologous end-joining pathway
Completed enrichment analysis of Non-small cell lung cancer pathway
Completed enrichment analysis of Notch signaling pathway pathway
Completed enrichment analysis of Nucleotide excision repair pathway
Completed enrichment analysis of Olfactory transduction pathway
Completed enrichment analysis of Oocyte meiosis pathway
Completed enrichment analysis of p53 signaling pathway pathway
Completed enrichment analysis of Pancreatic cancer pathway
Completed enrichment analysis of Pancreatic secretion pathway
Completed enrichment analysis of Parkinsons disease pathway
Completed enrichment analysis of Pathogenic Escherichia coli infection pathway
Completed enrichment analysis of Pathways in cancer pathway
Completed enrichment analysis of Peroxisome pathway
Completed enrichment analysis of Phagosome pathway
Completed enrichment analysis of Phosphatidylinositol signaling system pathway
Completed enrichment analysis of Phototransduction pathway
Completed enrichment analysis of PPAR signaling pathway pathway
Completed enrichment analysis of Primary immunodeficiency pathway
Completed enrichment analysis of Prion diseases pathway
Completed enrichment analysis of Progesterone-mediated oocyte maturation pathway
Completed enrichment analysis of Prostate cancer pathway
Completed enrichment analysis of Proteasome pathway
Completed enrichment analysis of Protein export pathway
Completed enrichment analysis of Protein processing in endoplasmic reticulum pathway
Completed enrichment analysis of Proximal tubule bicarbonate reclamation pathway
Completed enrichment analysis of Regulation of actin cytoskeleton pathway
Completed enrichment analysis of Regulation of autophagy pathway
Completed enrichment analysis of Renal cell carcinoma pathway
Completed enrichment analysis of Renin-angiotensin system pathway
Completed enrichment analysis of Ribosome pathway
Completed enrichment analysis of RIG-I-like receptor signaling pathway pathway
Completed enrichment analysis of RNA degradation pathway
Completed enrichment analysis of RNA polymerase pathway
Completed enrichment analysis of Salivary secretion pathway
Completed enrichment analysis of Shigellosis pathway
Completed enrichment analysis of Small cell lung cancer pathway
Completed enrichment analysis of SNARE interactions in vesicular transport pathway
Completed enrichment analysis of Spliceosome pathway
Completed enrichment analysis of Systemic lupus erythematosus pathway
Completed enrichment analysis of T cell receptor signaling pathway pathway
Completed enrichment analysis of Taste transduction pathway
Completed enrichment analysis of TGF-beta signaling pathway pathway
Completed enrichment analysis of Thyroid cancer pathway
Completed enrichment analysis of Tight junction pathway
Completed enrichment analysis of Toll-like receptor signaling pathway pathway
Completed enrichment analysis of Toxoplasmosis pathway
Completed enrichment analysis of Type I diabetes mellitus pathway
Completed enrichment analysis of Type II diabetes mellitus pathway
Completed enrichment analysis of Ubiquitin mediated proteolysis pathway
Completed enrichment analysis of Vascular smooth muscle contraction pathway
Completed enrichment analysis of Vasopressin-regulated water reabsorption pathway
Completed enrichment analysis of VEGF signaling pathway pathway
Completed enrichment analysis of Vibrio cholerae infection pathway
Completed enrichment analysis of Viral myocarditis pathway
Completed enrichment analysis of Wnt signaling pathway pathway
Number of significant genes from direct evidence
14
Number of significant genes from combined evidence
14
                                 Name No_of_Genes Sig_Direct Sig_Combi
1                   Adherens junction           7          4         4
2                          Amoebiasis           5          3         3
3 Arrhythmogenic right ventricular ca           6          3         3
4                      Focal adhesion           6          3         3
5 Leukocyte transendothelial migratio           6          3         3
6    Regulation of actin cytoskeleton           6          3         3
    p_Hyper p_Hyper_FWER p_PathNet p_PathNet_FWER
1 0.0852980            1 0.0852980              1
2 0.1261861            1 0.1261861              1
3 0.2079622            1 0.2079622              1
4 0.2079622            1 0.2079622              1
5 0.2079622            1 0.2079622              1
6 0.2079622            1 0.2079622              1
  gene_ID pDirectEvidence pIndirectEvidence pCombinedEvidence
1       1      0.03605423                NA        0.03605423
2       2      0.02017684                NA        0.02017684
3       9      0.28304995                NA        0.28304995
4      10      0.76640257                NA        0.76640257
5      12      0.51678700                NA        0.51678700
6      13      0.44507818                NA        0.44507818