Fig. 3

Examples of co-expressing genes differing in tumor vs. normal tissues. a Top 10 PARP2 co-expressing genes from tumor (by standard method or GRACE) or normal tissue samples. Top PARP2 co-expressing genes by standard method in tumors are dominated by genes from 14q, whereas top PARP2 co-expressing genes by GRACE in tumors contain many known cell cycle genes (genes marked in orange are from gene set “REACTOME_CELL_CYCLE”) pertinent to the known function of PARP2 in DNA repair. Top PARP2 co-expressing genes from normal tissues, however, do not contain cell cycle genes (genes marked in magenta are from gene family “Zinc fingers, C2H2-type”). b, c Frequencies of genes from “REACTOME_CELL_CYCLE” (b) or “Zinc fingers, C2H2-type” (c) in top 100 PARP2 co-expressing genes in tumor (by standard method or GRACE) or normal tissues from different TCGA cohorts. P values from hypergeometric tests were given next to the bars. In many TCGA cohorts, cell cycle genes are highly enriched in PARP2 co-expressing genes, and such enrichment is more significant with genes identified by GRACE than the standard method. In contrast, few cell cycle-related genes were found as PARP2 co-expressing genes in normal tissues; instead, zinc finger proteins are highly enriched. d Top 10 CCT4 co-expressing genes. Standard method found many CCT4 physical neighbors on chromosome 2p as co-expressing genes whereas GRACE found many other CCT subunits that are in the same complex with CCT4 (genes marked in orange belong to gene set “REACTOME_FORMATION_OF_TUBULIN_ FOLDING_INTERMEDIATES_BY_CCT_TRIC”). Top CCT4 co-expressing genes from normal tissues, however, do not contain CCT subunits. Instead, many ribosomal protein genes were found (genes marked in magenta belong to gene set “KEGG_RIBOSOME”) e, f Frequencies of genes from “REACTOME_FORMATION_OF_TUBULIN_ FOLDING_INTERMEDIATES_BY_CCT_TRIC” in top 20 CCT4 co-expressing genes (e) or “KEGG_RIBOSOME” (f) in top 100 CCT4 co-expressing genes. Analyses are based on TCGA BRCA data. P values from hypergeometric tests were given next to the bars. Abbreviations for TCGA cohorts: BRCA breast invasive carcinoma, COAD colon adenocarcinoma, HNSC head and neck squamous cell carcinoma, KICH kidney chromophobe, KIRC kidney renal clear cell carcinoma, KIRP kidney renal clear cell carcinoma, LIHC liver hepatocellular carcinoma, LUAD lung adenocarcinoma, LUSC lung squamous cell carcinoma, PRAD prostate adenocarcinoma