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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: GSE149214

Dataset summary for GSE149214

Datast informationDatasetGSE149214
PMID33712615
Raw data ID/linkPRJNA627676
OrganismHomo sapiens
SourcePC9 cell line
TissueCell line
Cancer type level1Lung cancer
Cancer type level2EGFR-mutated non-small cell lung cancer (NSCLC)
Regimenerlotinib
Drug typeTargeted therapy
Sample sizeresistant 1, sensitive 1
Cell number2393
Extract protocolDropSeq
Data processingCasava1.7
Public datePublic on Dec 19, 2020
DescriptionThis dataset has 1 cell line with a sensitive pre-treatment sample and a resistant post-treatment sample.

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Drug summary for GSE149214

Drug nameDrugBank IDDrug typeTargets nameTargets uniprot ID
"Erlotinib"

DB00530

small moleculeNR1I2; EGFRO75469; P00533

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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
Umap of cell clustersboxplotCell ratio of drug-resistant and sensitive groups within each clusterboxplot

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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

GSTM3

ENSG000001342020.3578963.32e-325.40e-280.3170.122Malignant cellsNA

PALLD

ENSG000001291160.3544131.32e-302.15e-260.4240.205Malignant cellsNA

RPSA

ENSG000001680280.3541241.23e-232.01e-190.5690.379Malignant cellsNA

THBS1

ENSG000001378010.3532441.54e-282.50e-240.3170.131Malignant cellsNA

ALDH1A3

ENSG000001842540.3527053.13e-265.09e-220.3810.193Malignant cellsNA

KTN1

ENSG000001267770.350682.79e-294.54e-250.9020.799Malignant cellsNA

TCF25

ENSG000001410020.3493445.27e-338.57e-290.3750.155Malignant cellsNA

RDX

ENSG000001377100.3419337.85e-271.28e-220.4290.226Malignant cellsNA

PAWR

ENSG000001774250.3392361.30e-272.12e-230.3990.194Malignant cellsNA

CSDE1

ENSG000000093070.3359771.23e-251.99e-210.5090.303Malignant cellsNA

CD24

ENSG000002723980.3317521.08e-291.75e-250.2890.104Malignant cellsNA

MT-CO1

ENSG000001988040.3292231.78e-282.90e-240.9940.986Malignant cellsNA

MAP1B

ENSG000001317110.3285791.65e-182.68e-140.5140.341Malignant cellsNA

PTTG1IP

ENSG000001832550.3161112.91e-274.74e-230.4130.208Malignant cellsNA

PTGR1

ENSG000001068530.3054793.80e-176.17e-130.5020.34Malignant cellsNA

FTH1

ENSG000001679960.3041722.57e-264.18e-220.9980.997Malignant cellsNA

YBX1

ENSG000000659780.2974184.06e-176.61e-130.7510.689Malignant cellsNA

GADD45A

ENSG000001167170.2966211.10e-311.79e-270.410.185Malignant cellsNA

SKIL

ENSG000001366030.2956472.31e-243.75e-200.3320.152Malignant cellsNA

SLC7A11

ENSG000001510120.2954311.87e-203.04e-160.3780.206Malignant cellsNA

APLP2

ENSG000000842340.2932074.57e-227.42e-180.3710.193Malignant cellsNA

RSF1

ENSG000000486490.288525.94e-239.66e-190.3830.195Malignant cellsNA

NCF2

ENSG000001167010.2877445.10e-308.30e-260.2820.096Malignant cellsNA

TES

ENSG000001352690.2860532.70e-194.39e-150.4240.256Malignant cellsNA

RPS27L

ENSG000001850880.2828321.51e-262.45e-220.3180.132Malignant cellsNA

GNAS

ENSG000000874600.281086.52e-201.06e-150.7640.666Malignant cellsNA

RPS27A

ENSG000001439470.2786923.55e-255.77e-210.9960.981Malignant cellsNA

RTF1

ENSG000001378150.277021.73e-192.81e-150.3730.207Malignant cellsNA

DEK

ENSG000001247950.2740351.67e-132.72e-090.8040.752Malignant cellsNA

CCNI

ENSG000001188160.2736841.22e-181.99e-140.4340.267Malignant cellsNA

PRDX6

ENSG000001175920.2735245.98e-199.72e-150.4560.285Malignant cellsNA

TALDO1

ENSG000001771560.2675081.20e-181.96e-140.4240.252Malignant cellsNA

PRDX1

ENSG000001174500.2663851.00e-121.63e-080.9370.934Malignant cellsNA

TMSB4X

ENSG000002055420.2654763.15e-235.12e-190.9990.982Malignant cellsNA

GSTK1

ENSG000001974480.2652746.81e-221.11e-170.30.137Malignant cellsNA

LUC7L3

ENSG000001088480.263771.97e-153.21e-110.4950.334Malignant cellsNA

RP11-622K12.1

NA0.2632061.63e-242.64e-200.2610.099Malignant cellsNA

UBXN4

ENSG000001442240.2631567.23e-161.18e-110.4210.27Malignant cellsNA

ACTN1

ENSG000000721100.2630984.88e-147.94e-100.4310.288Malignant cellsNA

HDLBP

ENSG000001156770.2592171.79e-202.92e-160.4770.282Malignant cellsNA

MT-CO3

ENSG000001989380.2576362.62e-174.26e-130.9960.99Malignant cellsNA

GOLGB1

ENSG000001732300.2535847.69e-171.25e-120.3950.233Malignant cellsNA

KRT18

ENSG000001110570.2528942.47e-114.01e-070.9520.933Malignant cellsNA

CAV2

ENSG000001059710.2527241.49e-182.42e-140.4310.258Malignant cellsNA

KRT7

ENSG000001354800.2504324.73e-157.69e-110.9760.959Malignant cellsNA

MT-ND3

ENSG00000198840-0.253088.73e-141.42e-090.7410.857Malignant cellsNA

SRSF9

ENSG00000111786-0.2556391.08e-171.76e-130.1510.286Malignant cellsNA

MT-ND2

ENSG00000198763-0.2559835.73e-139.31e-090.7850.9Malignant cellsNA

SNRPB

ENSG00000125835-0.258764.49e-167.30e-120.2450.389Malignant cellsNA

LMNA

ENSG00000160789-0.2589114.44e-157.22e-110.2180.352Malignant 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 Pathway2.40e-061.20e-051647811923467Malignant cellsGSTP1,HMGA1,PKM,S100A4,SOX4,ALDH1A3,ANXA1,CAV2,HSPD1,CAPNS1,FTL,LDHA,RSF1,S100A11,TPT1,YBX1,ENO1,GNAS,NUPR1
Irregularity in Drug Uptake and Drug Efflux2.80e-026.90e-0216437223467Malignant cellsSLC3A2,SLC7A11
Drug Inactivation by Structure Modification1.70e-012.90e-0116427123467Malignant cellsGSTP1
Aberration of the Drug's Therapeutic Target4.70e-015.90e-0116490123467Malignant cellsAKR1B1
Epigenetic Alteration of DNA, RNA or Protein8.30e-018.30e-01164455223467Malignant cellsLMNA,MALAT1


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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boxplot

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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
motifjaspar__MA1509.14.330.1IRF6 (directAnnotation). Malignant cells
motifmetacluster_22.134.20.0979MAFK (inferredBy_Orthology). Malignant cells
motiftransfac_pro__M058943.980.0945ZNF565 (directAnnotation). Malignant cells
motiftransfac_pro__M073013.910.0934NFATC4 (directAnnotation). Malignant cells
motiftransfac_pro__M055973.870.0928ZNF174 (directAnnotation). Malignant cells
motiftransfac_pro__M076083.820.0919ILF2; NFAT5; NFATC1; NFATC2; NFATC4 (directAnnotation). Malignant cells
motifmetacluster_22.113.760.091NFE2 (directAnnotation). Malignant cells
motifmetacluster_31.33.650.0894ZSCAN20; ZSCAN29 (directAnnotation). Malignant cells
motifmetacluster_22.213.620.0889NFE2L2 (inferredBy_Orthology). Malignant cells
motiftaipale_tf_pairs__HOXB13_TBX3_NNNRTAAATCACACNN_CAP_repr3.560.088HOXB13; TBX3 (directAnnotation). Malignant cells
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Motifs and TFs regulating down-regulated DEGs in resistant group
motifmotifNESAUCTF_highConfCell_type
motifmetacluster_56.56.620.128HSF1; HSF1; HSF2 (directAnnotation). HSF1; HSF2; HSF4; HSF5; HSFX1; HSFX2; HSFX3; HSFX4; HSFY1; HSFY2 (inferredBy_Orthology). Malignant cells
motifmetacluster_21.55.860.115HOXB2; HSF1; HSF1; HSF1; HSF1; HSF1; HSF1; HSF1; HSF1; HSF2; HSF2; HSF2; HSF2; HSF2; HSF2; HSF4; HSF4; HSF4 (directAnnotation). HSF1; HSF1; HSF1; HSF1; HSF1; HSF1; HSF1; HSF2; HSF2; HSF2; HSF2; HSF4; HSF4; HSF4; HSF4; HSF5; HSF5; HSF5; HSF5; HSFX1; HSFX1; HSFX1; HSFX1; HSFX2; HSFX2; HSFX2; HSFX2; HSFX3; HSFX3; HSFX3; HSFX3; HSFX4; HSFX4; HSFX4; HSFX4; HSFY1; HSFY1; HSFY1; HSFY1; HSFY2; HSFY2; HSFY2; HSFY2 (inferredBy_Orthology). Malignant cells
motifmetacluster_56.45.670.112HSF1; HSF2; HSF2; HSF4 (directAnnotation). Malignant cells
motifmetacluster_50.14.570.0942BATF; BATF; BATF; BATF; BNC2; FOS; FOSB; FOSL1; FOSL1; IRF4; JUN; JUN; JUNB; JUNB; JUNB; JUNB; JUND; JUND; JUND; JUND; JUND; SMAD2; SMAD3 (directAnnotation). BATF; BATF; BATF; FOS; FOSL1; FOSL2; JDP2; JUN; JUN; JUND (inferredBy_Orthology). Malignant cells
motiftransfac_pro__M058774.490.0928ZNF467 (inferredBy_Orthology). Malignant cells
motifmetacluster_157.24.310.0898ATF3; ATF3; ATF3; BACH1; BACH1; BACH1; BACH2; BACH2; BACH2; BACH2; BATF; BATF; BCL11A; FOS; FOS; FOS; FOS; FOS; FOS; FOSB; FOSL1; FOSL1; FOSL1; FOSL1; FOSL1; FOSL1; FOSL2; FOSL2; FOSL2; JDP2; JDP2; JDP2; JDP2; JDP2; JDP2; JDP2; JUN; JUN; JUN; JUN; JUN; JUNB; JUNB; JUNB; JUNB; JUNB; JUNB; JUND; JUND; JUND; JUND; JUND; JUND; JUND; JUND; JUND; MAF; MAFB; MAFF; MAFG; MAFK; NFE2; NFE2; NFE2; NFE2; NFE2; NFE2; NFE2L1; NFE2L1; NFE2L2; NFE2L3; ZNF3; ZSCAN5C (directAnnotation). FOSL1; JUN; JUN; JUN; JUNB; JUNB; JUND (inferredBy_Orthology). Malignant cells
motiftransfac_pro__M054744.210.0882ZNF639 (directAnnotation). Malignant cells
motiftaipale_tf_pairs__ERF_CEBPD_RSMGGAANTTGCGYAAN_CAP4.190.0878CEBPD; ERF (directAnnotation). Malignant cells
motiftransfac_pro__M069444.150.0872PRDM15 (directAnnotation). Malignant cells
motifcisbp__M001964.150.0872BBX (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

SOX4

tfdimers__MD00074upMalignant 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."