bio-pathway-wikipathways

WikiPathways Enrichment

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Install skill "bio-pathway-wikipathways" with this command: npx skills add gptomics/bioskills/gptomics-bioskills-bio-pathway-wikipathways

WikiPathways Enrichment

Core Pattern - Over-Representation Analysis

library(clusterProfiler) library(org.Hs.eg.db)

wp_result <- enrichWP( gene = entrez_ids, # Character vector of Entrez IDs organism = 'Homo sapiens', # Full species name pvalueCutoff = 0.05, pAdjustMethod = 'BH' )

head(as.data.frame(wp_result))

Prepare Gene List

de_results <- read.csv('de_results.csv') sig_genes <- de_results[de_results$padj < 0.05 & abs(de_results$log2FoldChange) > 1, 'gene_symbol']

gene_ids <- bitr(sig_genes, fromType = 'SYMBOL', toType = 'ENTREZID', OrgDb = org.Hs.eg.db) entrez_ids <- gene_ids$ENTREZID

GSEA on WikiPathways

Create ranked gene list

gene_list <- de_results$log2FoldChange names(gene_list) <- de_results$entrez_id gene_list <- sort(gene_list, decreasing = TRUE)

gsea_wp <- gseWP( geneList = gene_list, organism = 'Homo sapiens', pvalueCutoff = 0.05, pAdjustMethod = 'BH' )

head(as.data.frame(gsea_wp))

With Background Universe

all_genes <- de_results$entrez_id

wp_result <- enrichWP( gene = entrez_ids, universe = all_genes, organism = 'Homo sapiens', pvalueCutoff = 0.05 )

Make Results Readable

Convert Entrez IDs to gene symbols

wp_readable <- setReadable(wp_result, OrgDb = org.Hs.eg.db, keyType = 'ENTREZID')

Visualization

library(enrichplot)

Dot plot

dotplot(wp_result, showCategory = 15)

Bar plot

barplot(wp_result, showCategory = 15)

Gene-concept network

cnetplot(wp_readable, categorySize = 'pvalue')

Enrichment map

wp_result <- pairwise_termsim(wp_result) emapplot(wp_result)

Using rWikiPathways Directly

library(rWikiPathways)

List available organisms

listOrganisms()

Get all pathways for an organism

human_pathways <- listPathways('Homo sapiens')

Get pathway info

pathway_info <- getPathwayInfo('WP554') # ACE Inhibitor Pathway

Get genes in a pathway

pathway_genes <- getXrefList('WP554', 'H') # HGNC symbols pathway_entrez <- getXrefList('WP554', 'L') # Entrez IDs

Download pathway as GMT for custom analysis

downloadPathwayArchive(organism = 'Homo sapiens', format = 'gmt')

Custom GMT-Based Analysis

Download WikiPathways GMT

library(rWikiPathways) downloadPathwayArchive(organism = 'Homo sapiens', format = 'gmt', destpath = '.')

Read GMT and run enrichment

wp_gmt <- read.gmt('wikipathways-Homo_sapiens.gmt')

wp_custom <- enricher( gene = entrez_ids, TERM2GENE = wp_gmt, pvalueCutoff = 0.05 )

Different Organisms

Mouse

wp_mouse <- enrichWP(gene = mouse_entrez, organism = 'Mus musculus')

Rat

wp_rat <- enrichWP(gene = rat_entrez, organism = 'Rattus norvegicus')

Zebrafish

wp_zfish <- enrichWP(gene = zfish_entrez, organism = 'Danio rerio')

List all available organisms

library(rWikiPathways) listOrganisms()

Compare Clusters

gene_clusters <- list( upregulated = up_genes, downregulated = down_genes )

compare_wp <- compareCluster( geneClusters = gene_clusters, fun = 'enrichWP', organism = 'Homo sapiens', pvalueCutoff = 0.05 )

dotplot(compare_wp)

Export Results

results_df <- as.data.frame(wp_result) write.csv(results_df, 'wikipathways_enrichment.csv', row.names = FALSE)

Key Parameters

Parameter Default Description

gene required Vector of Entrez IDs

organism required Full species name

pvalueCutoff 0.05 P-value threshold

pAdjustMethod BH Adjustment method

universe NULL Background genes

minGSSize 10 Min genes per pathway

maxGSSize 500 Max genes per pathway

Common Organisms

Common Name Scientific Name

Human Homo sapiens

Mouse Mus musculus

Rat Rattus norvegicus

Zebrafish Danio rerio

Fruit fly Drosophila melanogaster

C. elegans Caenorhabditis elegans

Arabidopsis Arabidopsis thaliana

Yeast Saccharomyces cerevisiae

WikiPathways vs Other Databases

Feature WikiPathways KEGG Reactome

Curation Community Expert Peer-reviewed

License Open (CC0) Commercial Open

Species 30+ 4000+ 7

Focus Disease, drug Metabolic Signaling

Updates Continuous Ongoing Quarterly

Related Skills

  • go-enrichment - Gene Ontology enrichment

  • kegg-pathways - KEGG pathway enrichment

  • reactome-pathways - Reactome pathway enrichment

  • gsea - Gene Set Enrichment Analysis

  • enrichment-visualization - Visualization functions

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