Drug perturbation gene set enrichment analysis (dpGSEA): a new transcriptomic drug screening approach

BMC Bioinformatics

Table 1 A rank-ordered list by (A) ES and (B) TCS p value of positively correlated validation tests using an external RNA-seq dataset

Drug	ES	NES	ES p value	Genes	Proto-Matrix
A
paclitaxel_HT29	0.547	2.745	0.011	SCNN1A, AKR1C3	LINCS FC Rank 20
paclitaxel_HT29	0.742	2.863	0.014	CFAP70, C4BPB	LINCS Sig Rank 20
parbendazole_PC3	0.627	2.722	0.014	FSTL3, HIST1H2BG	CMAP FC Rank 20
fluvastatin_MCF7	0.295	2.509	0.016	IFIT1, MSMO1, INSIG1, HMGCR, IDI1, HSD17B7	CMAP FC Rank 50
fluvastatin_MCF7	0.377	2.515	0.016	SQLE, INSIG1, IDI1, SLCO4C1, MAP1S, RTEL1, PPIF, MAFK	CMAP Sig Rank 50
paclitaxel_MCF7	0.864	3.076	0.016	HSPB1	LINCS Sig Rank 10
paclitaxel_HT29	0.855	3.043	0.019	CFAP70, C4BPB	LINCS Sig Rank 10
doxorubicin_A375	0.529	2.588	0.020	MYB, CCL20, SLC27A2, MX2	LINCS FC Rank 20
paclitaxel_HELA	0.369	2.349	0.042	ABTB2, ZNF816, CASK	LINCS Sig Rank 50
paclitaxel_PC3	0.706	2.531	0.044	SIK1, GPM6A	LINCS FC Rank 20
parbendazole_MCF7	0.848	3.051	0.044	HIST1H2BG	CMAP Sig Rank 10

Drug	TCS	NTCS	TCS p value	Genes	Proto-Matrix
B
rosiglitazone_HELA	0.999	1.362	0.010	INSIG1	LINCS Sig Rank 50
paclitaxel_MCF7	0.979	1.671	0.031	HSPB1	LINCS Sig Rank 10
parbendazole_MCF7	0.954	1.929	0.044	HIST1H2BG	CMAP Sig Rank 10
paclitaxel_HA1E	0.992	1.336	0.054	HIST1H2BD	LINCS Sig Rank 50
paclitaxel_MCF7	0.981	1.500	0.056	HSPB1	LINCS Sig Rank 20
paclitaxel_HT29	0.962	1.641	0.066	CFAP70, C4BPB	LINCS Sig Rank 10
paclitaxel_MCF7	0.982	1.370	0.088	HSPB1	LINCS Sig Rank 50
paclitaxel_HT29	0.964	1.474	0.101	CFAP70, C4BPB	LINCS Sig Rank 20
parbendazole_PC3	0.964	1.419	0.113	FSTL3, HIST1H2BG	CMAP FC Rank 20
paclitaxel_HELA	0.949	1.504	0.117	SIK1	LINCS FC Rank 20
paclitaxel_PC3	0.915	1.562	0.146	GAA	LINCS Sig Rank 10
doxorubicin_MCF7	0.849	1.717	0.150	S100A2	LINCS FC Rank 10

Each row represents a positively identified drug (rosiglitazone, fluvastatin, parbendazole, paclitaxel, or doxorubicin) by dpGSEA in GEPNTs perturbation versus GEPNTs DMSO control DE of our first test case. All findings shown pass an FDR threshold of α = 0.05 for ES in A and TCS in B. The leading-edge driver genes are listed in the “Genes” column and the specific proto-matrix the positive results were detected in are listed in the “Proto-Matrix” column. Positively identified paclitaxel perturbations were most frequent while other drugs were found in only some of the proto-matrices utilized

ISSN: 1471-2105