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Center for Computational Systems Medicine
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Dataset summary

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Drug summary

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Umap of single cell types and conditions (resistant and sensitive)

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Comparison of cell composition between the resistant and sensitive groups (This dataset does not contain this module)

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Comparison of intra-tumor heterogeneity (ITH) and epithelial-mesenchymal transition (EMT) scores of malignant cells between the resistant and sensitive groups

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Difference of cell-cell interactions between the resistant and sensitive groups (This dataset does not contain this module)

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Differentially expressed genes (DEGs) between the resistant and sensitive groups for each cell type

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Mechanism analysis of drug resistance-related DEGs for each cell type in the pre-treatment samples (This dataset does not contain this module)

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Mechanism analysis of drug resistance-related DEGs for each cell type in the post-treatment samples (This dataset does not contain this module)

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Mechanism analysis of drug resistance-related DEGs for each cell type in one patient or cell lines

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MicroRNAs (miRNAs) regulating drug resistance-related DEGs for Malignant cells

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Motifs and transcription factors (TFs) regulating drug resistance-related DEGs for each cell type

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Differentially expressed genes act as transcription factors

Dataset: GSE138267

Dataset summary for GSE138267

Datast informationDatasetGSE138267
PMID33521652
Raw data ID/linkPRJNA575243
OrganismHomo sapiens
SourceCDX
TissueTumor tissue
Cancer type level1Lung cancer
Cancer type level2Small cell lung cancer (SCLC)
RegimenNA
Drug typeChemotherapy
Sample sizeresistant 4, sensitive 4
Cell number61001
Extract protocol10x genomics
Data processingCellRanger 2.0.0
Public datePublic on Feb 12, 2020
DescriptionThis dataset has 8 PDX.

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Drug summary for GSE138267

Drug nameDrugBank IDDrug typeTargets nameTargets uniprot ID
"" is not included in the drug list.

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Umap of single cell types and conditions (resistant and sensitive)

check buttonUmap of cell types and conditions (resistant and sensitive). If this dataset has both pre-treatment and post-treatment samples, the cell types were annotated together. If this dataset is a cell line dataset, the UMAP of cell clusters and the cell ratio of drug-resistant and sensitive groups within each cluster will also be shown. (If the image exists, the user can click on it to enlarge it in a new window.)
Umap of cell typesboxplotUmap of conditionsboxplot

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Comparison of cell composition between the resistant and sensitive groups

check buttonIn the pre-treatment samples, the cell composition of the resistant and sensitive groups were compared.
* represents significant difference.
(If the image exists, the user can click on it to enlarge it in a new window.)

check buttonIn the post-treatment samples, the cell composition of the resistant and sensitive groups were compared.
* represents significant difference.
(If the image exists, the user can click on it to enlarge it in a new window.)

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Comparison of ITH and EMT scores of malignant cells between the resistant and sensitive groups

check buttonComparison of ITH (intra-tumoral heterogeneity) and EMT (epithelial-mesenchymal transition) scores of malignant cells between the resistant and sensitive groups. ITH represents intratumoral heterogeneity, EMT represents epithelial mesenchymal transition, pre represents pre-treatment, post represents post-treatment, post2 represents longer post-treatment. (If the image exists, the user can click on it to enlarge it in a new window.)
Comparison of ITH scoresboxplotComparison of EMT scoresboxplot

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Difference of cell-cell interactions between the resistant and sensitive groups

check buttonIn the pre-treatment samples, the difference in cell-cell interactions between the resistant and sensitive groups was compared. The numbers indicate the count of cell-cell interactions that were either higher or lower in the resistant group compared to the sensitive group. The dot plots of significant ligand-receptor pairs in the resistant group and sensitive group are subsequently displayed. (If the image exists, the user can click on it to enlarge it in a new window. Complete files can be downloaded from the download section.)

check buttonIn the post-treatment samples, the difference in cell-cell interactions between the resistant and sensitive groups was compared. The numbers indicate the count of cell-cell interactions that were either higher or lower in the resistant group compared to the sensitive group. The dot plots of significant ligand-receptor pairs in the resistant group and sensitive group are subsequently displayed. (If the image exists, the user can click on it to enlarge it in a new window. Complete files can be downloaded from the download section.)

check buttonThis dataset only has one patient or is a cell line dataset, the resistant sample is the post-treatment sample and the sensitive sample is the pre-treatment sample. The difference in cell-cell interactions between the resistant and sensitive groups was compared. The numbers indicate the count of cell-cell interactions that were either higher or lower in the resistant group compared to the sensitive group. The dot plots of significant ligand-receptor pairs in the resistant group and sensitive group are subsequently displayed. (If the image exists, the user can click on it to enlarge it in a new window. Complete files can be downloaded from the download section.)

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Differentially expressed genes (DEGs) between the resistant and sensitive groups for each cell type

check buttonIn the pre-treatment samples, the differentially expressed genes (|avg_log2FC|>0.25 & p_val_adj<0.05) between the resistant and sensitive groups for each cell type.

check buttonIn the post-treatment samples, the differentially expressed genes (|avg_log2FC|>0.25 & p_val_adj<0.05) between the resistant and sensitive groups for each cell type.

check buttonThis dataset only has one patient or is a cell line dataset, the resistant sample is the post-treatment sample and the sensitive sample is the pre-treatment sample. The following are differentially expressed genes (|avg_log2FC|>0.25 & p_val_adj<0.05) between the resistant and sensitive groups for each cell type.
Gene symbolGene idavg_log2FCp_valp_val_adjpct.1pct.2Cell typeTimepoint

BBX

ENSG000001144390.4331480.00e+000.00e+000.5040.275Malignant cellsNA

PSMD1

ENSG000001736920.433090.00e+000.00e+000.5170.228Malignant cellsNA

UBE3A

ENSG000001140620.4326090.00e+000.00e+000.4870.223Malignant cellsNA

ADAR

ENSG000001607100.4318910.00e+000.00e+000.4570.199Malignant cellsNA

CCNB1

ENSG000001340570.4309670.00e+000.00e+000.2840.204Malignant cellsNA

PANK2

ENSG000001257790.4306670.00e+000.00e+000.5040.225Malignant cellsNA

PRKAR1A

ENSG000001089460.4305920.00e+000.00e+000.7290.671Malignant cellsNA

TMEM57

NA0.4286960.00e+000.00e+000.3870.105Malignant cellsNA

RPL11

ENSG000001426760.4286750.00e+000.00e+0011Malignant cellsNA

CALM3

ENSG000001600140.4277790.00e+000.00e+000.8690.832Malignant cellsNA

NUP62

ENSG000002130240.425770.00e+000.00e+000.5410.287Malignant cellsNA

MINOS1

NA0.4256120.00e+000.00e+000.8630.759Malignant cellsNA

EPC1

ENSG000001206160.4246790.00e+000.00e+000.5190.265Malignant cellsNA

UBB

ENSG000001703150.424620.00e+000.00e+000.9990.998Malignant cellsNA

ZNF292

ENSG000001889940.4231270.00e+000.00e+000.5060.254Malignant cellsNA

ZIC2

ENSG000000433550.4231220.00e+000.00e+000.3330.097Malignant cellsNA

LINC00493

NA0.4225360.00e+000.00e+000.8120.676Malignant cellsNA

MAT2A

ENSG000001689060.4215290.00e+000.00e+000.5040.247Malignant cellsNA

KDM1A

ENSG000000044870.4209580.00e+000.00e+000.50.245Malignant cellsNA

SGK1

ENSG000001185150.4205290.00e+000.00e+000.2830.071Malignant cellsNA

KDELR1

ENSG000001054380.4197210.00e+000.00e+000.8660.858Malignant cellsNA

TRMT6

ENSG000000891950.4194090.00e+000.00e+000.4650.187Malignant cellsNA

ARHGEF2

ENSG000001165840.4192680.00e+000.00e+000.4740.217Malignant cellsNA

NUDC

ENSG000000902730.4186110.00e+000.00e+000.9430.877Malignant cellsNA

ATP5F1

NA0.4182870.00e+000.00e+000.890.793Malignant cellsNA

ARL6IP1

ENSG000001705400.4178132.58e-257.20e-210.8040.84Malignant cellsNA

SYTL1

ENSG000001427650.4170760.00e+000.00e+000.3660.126Malignant cellsNA

PHIP

ENSG000001462470.4168740.00e+000.00e+000.7270.696Malignant cellsNA

CDKN3

ENSG000001005260.41680.00e+000.00e+000.3430.236Malignant cellsNA

DDX24

ENSG000002737610.4164770.00e+000.00e+000.7980.739Malignant cellsNA

TP73

ENSG000000789000.4162240.00e+000.00e+000.3750.122Malignant cellsNA

RBP7

ENSG000001624440.4161810.00e+000.00e+000.2980.086Malignant cellsNA

DNAJC8

ENSG000002853170.4157850.00e+000.00e+000.7710.668Malignant cellsNA

CACNB3

ENSG000001675350.4155520.00e+000.00e+000.4090.165Malignant cellsNA

PRPF40A

ENSG000001965040.4149070.00e+000.00e+000.7670.742Malignant cellsNA

ZFP36

ENSG000001280160.4145480.00e+000.00e+000.5460.558Malignant cellsNA

CKAP2

ENSG000001361080.414460.00e+000.00e+000.3570.19Malignant cellsNA

UBE2E3

ENSG000001700350.4134330.00e+000.00e+000.8640.832Malignant cellsNA

NAT14

ENSG000000909710.4121430.00e+000.00e+000.5190.254Malignant cellsNA

CELF2

ENSG000000487400.4120520.00e+000.00e+000.3280.116Malignant cellsNA

JADE1

ENSG000000776840.4111930.00e+000.00e+000.3640.137Malignant cellsNA

U2AF2

ENSG000000632440.4108770.00e+000.00e+000.570.296Malignant cellsNA

NRXN1

ENSG000001799150.4101880.00e+000.00e+000.3970.165Malignant cellsNA

RAB30-AS1

NA0.4095360.00e+000.00e+000.4490.199Malignant cellsNA

CEBPB

ENSG000001722160.4089770.00e+000.00e+000.6270.567Malignant cellsNA

CENPV

ENSG000001665820.4089070.00e+000.00e+000.7830.773Malignant cellsNA

CMIP

ENSG000001538150.4086140.00e+000.00e+000.4960.268Malignant cellsNA

PITHD1

ENSG000000577570.4083780.00e+000.00e+000.6540.538Malignant cellsNA

MIDN

ENSG000001674700.4083520.00e+000.00e+000.4880.215Malignant cellsNA

RBM39

ENSG000001310510.4083410.00e+000.00e+000.9480.9Malignant cellsNA
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Mechanism analysis of drug resistance-related DEGs for each cell type in the pre-treatment samples

check buttonEnrichment results for 5 known drug-resistant mechanisms in malignant cells and 1 known mechanism in TME cells.The "Signature" column represents the differentially expressed genes (DEGs) used for enrichment. The "Geneset" column represents the genes included in this mechanism. The "Overlap" column represents the number of genes in the "Geneset" that are enriched in the "Signature". The "Enriched Genes" column represents the genes in the "Geneset" that are enriched in the "Signature". (If the image exists, the user can click on it to enlarge it in a new window.)

check buttonHallmark, KEGG and GOBP enrichment results for up-regulated genes in resistant group of pre-treatment samples. Only show the top 50 pathways with fdr<0.05. If certain cell types are not displayed, it means that there are no significant pathways based on DEGs in those cell types. (If the image exists, the user can click on it to enlarge it in a new window. Complete files can be downloaded from the download section.)

check buttonHallmark, KEGG and GOBP enrichment results for down-regulated genes in resistant group of pre-treatment samples. Only show the top 50 pathways with fdr<0.05. If certain cell types are not displayed, it means that there are no significant pathways based on DEGs in those cell types. (If the image exists, the user can click on it to enlarge it in a new window.Complete files can be downloaded from the download section.)

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Mechanism analysis of drug resistance-related DEGs for each cell type in the post-treatment samples

check buttonEnrichment results for 5 known drug resistance mechanisms in malignant cells and 1 known mechanism in TME cells.The "Signature" column represents the differentially expressed genes (DEGs) used for enrichment. The "Geneset" column represents the genes included in this mechanism. The "Overlap" column represents the number of genes in the "Geneset" that are enriched in the "Signature". The "Enriched Genes" column represents the genes in the "Geneset" that are enriched in the "Signature". (If the image exists, the user can click on it to enlarge it in a new window.)

check buttonHallmark, KEGG and GOBP enrichment results for up-regulated genes in resistant group of post-treatment samples. Only show the top 50 pathways with fdr<0.05. If certain cell types are not displayed, it means that there are no significant pathways based on DEGs in those cell types. (If the image exists, the user can click on it to enlarge it in a new window. Complete files can be downloaded from the download section.)

check buttonHallmark, KEGG and GOBP enrichment results for down-regulated genes in resistant group of post-treatment samples. Only show the top 50 pathways with fdr<0.05. If certain cell types are not displayed, it means that there are no significant pathways based on DEGs in those cell types. (If the image exists, the user can click on it to enlarge it in a new window. Complete files can be downloaded from the download section.)

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Mechanism analysis of drug resistance-related DEGs for each cell type in one patient or cell lines

check buttonThis dataset only has one patient or is a cell line dataset, the resistant sample is the post-treatment sample and the sensitive sample is the pre-treatment sample. Enrichment results for 5 known drug resistance mechanisms in malignant cells and 1 known mechanism in TME cells are shown here.The "Signature" column represents the differentially expressed genes (DEGs) used for enrichment. The "Geneset" column represents the genes included in this mechanism. The "Overlap" column represents the number of genes in the "Geneset" that are enriched in the "Signature". The "Enriched Genes" column represents the genes in the "Geneset" that are enriched in the "Signature". (If the image exists, the user can click on it to enlarge it in a new window.)
Enrichment results for 5 known drug resistance mechanisms in malignant cells
boxplot
MechnismPvalFDRSignatureGenesetOverlapBackgroundCell typeEnriched Genes
Unusual Activation of Pro-survival Pathway3.30e-151.60e-14131978110123467Malignant cellsAKAP1,ANXA2,ATG12,AURKA,CDK4,CDKN1B,TP53,CIAPIN1,DLK1,GSTP1,SLC2A1,HIF1A,HMGA1,HOXB3,ID1,IDH2,IFI27,ISG15,PKM,RPS6,SOX2,SOX4,STMN1,TPD52,TYMS,SLC25A5,TFAP2A,ARID1A,ATG4B,BNIP2,BRD4,BRD7,CCNB1,CDK1,CCNG1,ALCAM,CDC27,CDKN2A,CRBN,CREB1,CXCR4,DCK,DNMT3A,DHFR,EHF,ERCC1,EZR,FIS1,FTL,GAPDH,GAS6,NR3C1,HAX1,HDAC1,HMGB2,HMGN5,HNRNPU,HSPB1,EIF4A3,TCF4,KDM5B,KLF4,LDHA,LRRFIP1,MDM4,MYBL2,NQO1,NUCKS1,TP73,PABPC1,AGPAT2,PTPN1,HRAS,REV1,RRM2,RSF1,SDHB,SMC4,SOCS3,SRSF2,STAT3,SUZ12,TMEM54,TOP1,TUSC3,UBE2C,USP14,USP22,UCP2,WLS,YBX1,ENO1,GNAS,CALR,EIF4EBP1,BRD2,NKX2-1,G3BP1,PMVK,EBP,CERS6
Drug Inactivation by Structure Modification1.90e-014.00e-01131927323467Malignant cellsGSTP1,DCK,CMPK1
Aberration of the Drug's Therapeutic Target2.40e-014.00e-01131990723467Malignant cellsCDK4,TP53,IDH2,CDKN2A,CRBN,DHFR,TOP2A
Irregularity in Drug Uptake and Drug Efflux3.50e-014.30e-01131937323467Malignant cellsSLC3A2,SLC2A1,TAP1
Epigenetic Alteration of DNA, RNA or Protein9.90e-019.90e-0113194551623467Malignant cellsTP53,H2AFY,IDH2,EIF4G2,LMNA,TYMS,PMAIP1,CDKN2A,CXCR4,DNMT3A,GAPDH,SMC4,TIMP1,MALAT1,GDI2,MT-CO2


check buttonHallmark, KEGG and GOBP enrichment results for up-regulated genes in resistant group. Only show the top 50 pathways with fdr<0.05. If certain cell types are not displayed, it means that there are no significant pathways based on DEGs in those cell types. (If the image exists, the user can click on it to enlarge it in a new window. Complete files can be downloaded from the download section.)
Up-regulated HallmarkUp-regulated KEGGUp-regulated GO BP

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check buttonHallmark, KEGG and GOBP enrichment results for down-regulated genes in resistant group. Only show the top 50 pathways with fdr<0.05. If certain cell types are not displayed, it means that there are no significant pathways based on DEGs in those cell types. (If the image exists, the user can click on it to enlarge it in a new window. Complete files can be downloaded from the download section.)
Down-regulated HallmarkDown-regulated KEGGDown-regulated GO BP

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boxplot

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MicroRNAs (miRNAs) regulating drug resistance-related DEGs for malignant cells

check buttonIn the pre-treatment samples, the miRNAs with a score greater than 80 that regulate the top10 abs(avg_log2FC) drug resistance-related DEGs for malignant cells are shown here. If the gene does not have any miRNAs with a score greater than 80, it will not be shown. Here only the names of miRNAs with a score greater than 90 are shown, but some names will not be shown because of too many overlaps. (Complete files containing all datasets and cell types can be downloaded from the download section.)

check buttonIn the post-treatment samples, the miRNAs with a score greater than 80 that regulate the top10 abs(avg_log2FC) drug resistance-related DEGs for Malignant cells are shown here. If the gene does not have any miRNAs with a score greater than 80, it will not be shown. Here only the names of miRNAs with a score greater than 90 are shown, but some names will not be shown because of too many overlaps. (Complete files containing all datasets and cell types can be downloaded from the download section.)

check buttonThis dataset only has one patient or is a cell line dataset, the resistant sample is the post-treatment sample and the sensitive sample is the pre-treatment sample. The miRNAs with a score greater than 80 that regulate the top10 abs(avg_log2FC) drug resistance-related DEGs for Malignant cells are shown here. Here only the names of miRNAs with a score greater than 80 are shown, but some names will not be shown because of too many overlaps. If the gene does not have any miRNAs with a score greater than 90, it will not be shown. (Complete files containing all datasets and cell types can be downloaded from the download section.)
Regulating up-regulated DEGs in resistant groupRegulating down-regulated DEGs in resistant group
boxplotboxplot

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Motifs and transcription factors (TFs) regulating drug resistance-related DEGs for each cell type

check buttonIn the pre-treatment samples, the motifs and TFs that regulate drug resistance-related DEGs for each cell type are shown here. (Complete files can be downloaded from the download section.)

check buttonIn the post-treatment samples, the motifs and TFs that regulate drug resistance-related DEGs for each cell type are shown here. (Complete files can be downloaded from the download section.)

check buttonThis dataset only has one patient or is a cell line dataset, the resistant sample is the post-treatment sample and the sensitive sample is the pre-treatment sample. Motifs and TFs that regulate drug resistance-related DEGs for each cell type are shown here. (Complete files can be downloaded from the download section.)
Motifs and TFs regulating up-regulated DEGs in resistant group
motifmotifNESAUCTF_highConfCell_type
motiftaipale_tf_pairs__GCM1_SPDEF_RTGNKGGCGGAWG_CAP_repr3.630.0606GCM1; SPDEF (directAnnotation). Malignant cells
motiftransfac_pro__M012193.550.06SP1 (directAnnotation). SP3 (inferredBy_Orthology). Malignant cells
motiftransfac_pro__M073973.530.0598ZNF148 (directAnnotation). Malignant cells
motifmetacluster_131.73.430.059EGR1; EGR1; EGR1; EGR1; EGR1; EGR1; EGR1; EGR1; EGR1; EGR1; EGR1; EGR1; EGR1; EGR1; EGR1; EGR1; EGR1; EGR2; EGR2; EGR2; EGR2; EGR2; EGR2; EGR3; EGR3; EGR3; EGR3; EGR3; EGR3; EGR4; EGR4; WT1 (directAnnotation). EGR1; EGR1; EGR1; EGR1; EGR1; EGR2; EGR2; EGR2; EGR2; EGR2; EGR3; EGR3; WT1; ZBTB43; ZBTB43; ZBTB43; ZBTB43; ZBTB5; ZBTB5; ZBTB5; ZBTB5; ZBTB7A; ZBTB7A; ZBTB7A; ZBTB7A; ZNF367; ZNF367; ZNF367; ZNF367; ZNF740; ZNF740; ZNF740; ZNF740 (inferredBy_Orthology). Malignant cells
motifmetacluster_131.43.390.0587EGR2; EGR2; ZFHX2; ZNF141 (directAnnotation). Malignant cells
motifdbtfbs__GMEB1_K562_ENCSR928KOR_merged_N13.370.0585GMEB1 (directAnnotation). Malignant cells
motiftaipale_cyt_meth__ZNF281_NCCCCTCCCCCN_eDBD_meth3.350.0584ZNF281 (directAnnotation). Malignant cells
motifmetacluster_15.23.330.0583E2F1; E2F1; E2F1; E2F1; E2F1; E2F3; E2F4; E2F4; E2F4; E2F6; E2F6; E2F6; E2F6; E2F6; E2F6; E2F6; E2F7; TFDP1; TFDP2; ZNF566; ZNF566; ZNF574 (directAnnotation). E2F3; E2F3; E2F4 (inferredBy_Orthology). Malignant cells
motifmetacluster_7.133.320.0582ZFX (directAnnotation). Malignant cells
motifmetacluster_3.113.320.0582SP1; SP1; SP2; SP3; SP3; SP4 (directAnnotation). Malignant cells
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Motifs and TFs regulating down-regulated DEGs in resistant group
motifmotifNESAUCTF_highConfCell_type
motiftaipale_tf_pairs__ETS2_RCCGGAAGTG_HT4.280.0499ETS2 (directAnnotation). Malignant cells
motifjaspar__MA1483.23.940.0476ELF2 (directAnnotation). Malignant cells
motiftransfac_pro__M054813.920.0474ZNF202 (directAnnotation). Malignant cells
motiftransfac_pro__M058463.630.0454ZNF689 (directAnnotation). Malignant cells
motiftransfac_pro__M068273.580.045ZBTB11 (directAnnotation). Malignant cells
motiftaipale_tf_pairs__MYBL1_ELF1_NMCCGGAACCGTTR_CAP_repr3.570.0449ELF1; MYBL1 (directAnnotation). Malignant cells
motiftransfac_pro__M055223.520.0446ZNF341 (directAnnotation). Malignant cells
motifswissregulon__hs__ETV63.490.0444ETV6 (directAnnotation). Malignant cells
motiftransfac_pro__M052983.420.0439OVOL3 (directAnnotation). Malignant cells
motifmetacluster_33.53.350.0434MTF1 (inferredBy_Orthology). Malignant cells
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Differentially expressed genes act as transcription factors

check buttonThis table shows the differentially expressed genes that act as transcription factors. (Complete files can be downloaded from the download section.)
TFmotifExpressionCell typeTimepoint

ETS2

taipale_tf_pairs__ETS2_RCCGGAAGTG_HTupMalignant cellsNA

ELF2

jaspar__MA1483.2upMalignant cellsNA

ELF2

taipale_tf_pairs__ELF2_NATGCGGAAGTR_HTupMalignant cellsNA

TFAP2A

tfdimers__MD00275upMalignant cellsNA

HES6

jaspar__MA1493.1upMalignant cellsNA

CHD2

metacluster_172.6upMalignant cellsNA

ZNF281

taipale_cyt_meth__ZNF281_NCCCCTCCCCCN_eDBD_methupMalignant cellsNA

SP3

metacluster_3.11upMalignant cellsNA

SP3

metacluster_3.7upMalignant cellsNA

NR3C1

metacluster_141.5upMalignant cellsNA
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1"Sun X, Zhang Y, Li H, Zhou Y, Shi S, Chen Z, He X, Zhang H, Li F, Yin J, Mou M, Wang Y, Qiu Y, Zhu F. DRESIS: the first comprehensive landscape of drug resistance information. Nucleic Acids Res. 2023 Jan 6;51(D1):D1263-D1275. doi: 10.1093/nar/gkac812. PMID: 36243960; PMCID: PMC9825618."
2"Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037. PMID: 29126136; PMCID: PMC5753335."