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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 (This dataset does not contain this module)

Dataset: GSE158457

Dataset summary for GSE158457

Datast informationDatasetGSE158457
PMID34151288
Raw data ID/linkPRJNA665257
OrganismHomo sapiens
SourcePDX cells
TissueCell line
Cancer type level1Acute lymphoblastic leukemia
Cancer type level2T-cell acute lymphoblastic leukemia (ALL)
Regimendasatinib
Drug typeTargeted therapy
Sample sizeresistant 2, sensitive 2
Cell number26026
Extract protocol10x genomics
Data processingCellRanger 3.1.0
Public datePublic on Jan 05, 2021
DescriptionThe dataset has 2 patient-derived PDX cell groups, each with a sensitive pre-treatment sample and a resistant post-treatment sample.

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Drug summary for GSE158457

Drug nameDrugBank IDDrug typeTargets nameTargets uniprot ID
"Dasatinib"

DB01254

small moleculeABL1; SRC; EPHA2; LCK; YES1; KIT; PDGFRB; STAT5B; ABL2; FYN; BTK; NR4A3; BCR; CSK; EPHA5; EPHB4; FGR; FRK; HSPA8; LYN; ZAK; MAPK14; PPATP00519; P12931; P29317; P06239; P07947; P10721; P09619; P51692; P42684; P06241; Q06187; Q92570; P11274; P41240; P54756; P54760; P09769; P42685; P11142; P07948; Q9NYL2; Q16539; Q06203

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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

RPA3

ENSG00000106399-0.2713780.00e+000.00e+000.3840.54Malignant cellsNA

ERH

ENSG00000100632-0.2718410.00e+000.00e+000.6550.762Malignant cellsNA

HMGB1

ENSG00000189403-0.2729782.04e-403.88e-360.9990.997Malignant cellsNA

CKS2

ENSG00000123975-0.2761450.00e+000.00e+000.3040.415Malignant cellsNA

RPL4

ENSG00000174444-0.2785280.00e+000.00e+000.9920.997Malignant cellsNA

FEN1

ENSG00000168496-0.2785840.00e+000.00e+000.1960.328Malignant cellsNA

HNRNPD

ENSG00000138668-0.2790580.00e+000.00e+000.7370.814Malignant cellsNA

PAICS

ENSG00000128050-0.279940.00e+000.00e+000.2370.416Malignant cellsNA

GTSE1

ENSG00000075218-0.2799680.00e+000.00e+000.170.297Malignant cellsNA

RAD21

ENSG00000164754-0.2836240.00e+000.00e+000.5770.705Malignant cellsNA

HNRNPAB

ENSG00000197451-0.2842650.00e+000.00e+000.4320.566Malignant cellsNA

MAD2L1

ENSG00000164109-0.2845150.00e+000.00e+000.3080.454Malignant cellsNA

PRDX2

ENSG00000167815-0.2849460.00e+000.00e+000.6210.731Malignant cellsNA

SPINK2

ENSG00000128040-0.2854160.00e+000.00e+000.2070.314Malignant cellsNA

RPS6

ENSG00000137154-0.2863180.00e+000.00e+000.9991Malignant cellsNA

TUBA1C

ENSG00000167553-0.2864010.00e+000.00e+000.220.325Malignant cellsNA

CASC5

NA-0.286810.00e+000.00e+000.1770.316Malignant cellsNA

CLSPN

ENSG00000092853-0.2878440.00e+000.00e+000.1780.318Malignant cellsNA

VIM

ENSG00000026025-0.2933260.00e+000.00e+000.8740.959Malignant cellsNA

CARHSP1

ENSG00000153048-0.2940910.00e+000.00e+000.5320.661Malignant cellsNA

USP1

ENSG00000162607-0.2943490.00e+000.00e+000.3420.484Malignant cellsNA

RPLP0

ENSG00000089157-0.2947610.00e+000.00e+000.9960.999Malignant cellsNA

FABP5

ENSG00000164687-0.2974530.00e+000.00e+000.3830.557Malignant cellsNA

UBE2T

ENSG00000077152-0.2984730.00e+000.00e+000.1930.342Malignant cellsNA

LMNB1

ENSG00000113368-0.3047280.00e+000.00e+000.2740.437Malignant cellsNA

CKS1B

ENSG00000173207-0.3054760.00e+000.00e+000.260.41Malignant cellsNA

NUCKS1

ENSG00000069275-0.3097420.00e+000.00e+000.730.805Malignant cellsNA

RRM1

ENSG00000167325-0.3118370.00e+000.00e+000.2170.369Malignant cellsNA

TMPO

ENSG00000120802-0.3125220.00e+000.00e+000.5870.707Malignant cellsNA

RPSA

ENSG00000168028-0.3188510.00e+000.00e+000.9991Malignant cellsNA

YBX1

ENSG00000065978-0.3189030.00e+000.00e+000.9870.995Malignant cellsNA

PPIA

ENSG00000196262-0.3229350.00e+000.00e+000.9580.977Malignant cellsNA

DARS

NA-0.3238740.00e+000.00e+000.3170.495Malignant cellsNA

SNRPB

ENSG00000125835-0.3261410.00e+000.00e+000.6170.755Malignant cellsNA

MT-CO3

ENSG00000198938-0.3263310.00e+000.00e+0011Malignant cellsNA

TPX2

ENSG00000088325-0.328990.00e+000.00e+000.1860.318Malignant cellsNA

BIRC5

ENSG00000089685-0.3300790.00e+000.00e+000.1570.299Malignant cellsNA

CENPM

ENSG00000100162-0.3309780.00e+000.00e+000.1710.329Malignant cellsNA

NASP

ENSG00000132780-0.3330640.00e+000.00e+000.5890.71Malignant cellsNA

FAM162A

ENSG00000114023-0.333840.00e+000.00e+000.220.354Malignant cellsNA

KPNA2

ENSG00000182481-0.3350790.00e+000.00e+000.2170.309Malignant cellsNA

HMGB3

ENSG00000029993-0.3353140.00e+000.00e+000.2190.375Malignant cellsNA

HMGA1

ENSG00000137309-0.3382570.00e+000.00e+000.3430.511Malignant cellsNA

LSM4

ENSG00000130520-0.3399220.00e+000.00e+000.4830.639Malignant cellsNA

ANP32B

ENSG00000136938-0.3409690.00e+000.00e+000.8340.92Malignant cellsNA

GPI

ENSG00000282019-0.343910.00e+000.00e+000.1140.279Malignant cellsNA

HNRNPA2B1

ENSG00000122566-0.3473650.00e+000.00e+000.9790.982Malignant cellsNA

RCBTB2

ENSG00000136161-0.3495090.00e+000.00e+000.6480.776Malignant cellsNA

NAP1L1

ENSG00000187109-0.3516430.00e+000.00e+000.8660.934Malignant cellsNA

H2AFV

NA-0.3521420.00e+000.00e+000.7840.877Malignant 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
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MechnismPvalFDRSignatureGenesetOverlapBackgroundCell typeEnriched Genes
Unusual Activation of Pro-survival Pathway5.20e-142.60e-131467812823467Malignant cellsBIRC5,DNMT1,HMGA1,HMGB1,PKM,RPS6,STMN1,TYMS,ANXA1,BTG1,CDK1,DHFR,GAPDH,HMGB2,HNRNPU,KIF11,LDHA,MDM4,NUCKS1,PGK1,RRM1,RRM2,SMC4,SRSF2,UBE2C,YBX1,ENO1,NPM1
Aberration of the Drug's Therapeutic Target1.90e-024.70e-0214690323467Malignant cellsDHFR,NPM1,TOP2A
Epigenetic Alteration of DNA, RNA or Protein1.50e-012.60e-01146455523467Malignant cellsDNMT1,TYMS,GAPDH,SMC4,MALAT1
Drug Inactivation by Structure Modification1.00e+001.00e+0014627023467Malignant cells
Irregularity in Drug Uptake and Drug Efflux1.00e+001.00e+0014637023467Malignant cells


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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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
motiftransfac_pro__M021085.050.188NKX2-5 (directAnnotation). Malignant cells
motifmetacluster_160.54.390.168ZNF189; ZNF189; ZNF341 (directAnnotation). Malignant cells
motifhdpi__VAX24.30.166VAX2 (directAnnotation). Malignant cells
motifmetacluster_141.44.290.165GLIS2 (directAnnotation). Malignant cells
motifmetacluster_135.34.120.16ZNF486 (directAnnotation). Malignant cells
motifmetacluster_19.14.010.157GMEB2; GMEB2; GMEB2 (directAnnotation). Malignant cells
motifhocomoco__TYY2_HUMAN.H11MO.0.D4.010.157YY2 (directAnnotation). Malignant cells
motiftransfac_pro__M0484340.157SMC3 (directAnnotation). Malignant cells
motifswissregulon__hs__SMAD340.157SMAD3 (directAnnotation). Malignant cells
motiftransfac_pro__M061603.840.152ZNF92 (directAnnotation). Malignant cells
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Motifs and TFs regulating down-regulated DEGs in resistant group
motifmotifNESAUCTF_highConfCell_type
motifmetacluster_174.28.010.128CEBPZ; CEBPZ; DRAP1; FOS; FOXI1; FOXI1; HMGXB3; IRF3; NFYA; NFYA; NFYA; NFYA; NFYA; NFYA; NFYA; NFYA; NFYA; NFYB; NFYB; NFYB; NFYB; NFYB; NFYC; NFYC; NFYC; NFYC; NFYC; NFYC; NFYC; PBX3; PBX3; SP2 (directAnnotation). NFYA; NFYA; NFYC; PBX1; PBX3 (inferredBy_Orthology). Malignant cells
motifmetacluster_174.37.790.125MBD2; NFYA; NFYB; NFYC; PBX3 (directAnnotation). Malignant cells
motifmetacluster_174.67.750.125NFYA; NFYB; NFYB; NFYC (directAnnotation). Malignant cells
motifswissregulon__mm__E2f75.560.0968E2F7 (inferredBy_Orthology). Malignant cells
motifmetacluster_45.65.170.0918E2F1; E2F1; E2F1; E2F1; E2F1; E2F2; E2F2; E2F2; E2F3; E2F3; E2F3; E2F4; E2F4 (directAnnotation). E2F2; E2F3 (inferredBy_Orthology). Malignant cells
motifmetacluster_102.25.140.0914ZBED1 (directAnnotation). Malignant cells
motiftransfac_pro__M068944.730.0862ZFP90 (inferredBy_Orthology). Malignant cells
motiftransfac_pro__M054744.60.0845ZNF639 (directAnnotation). Malignant cells
motifcisbp__M008084.590.0843MYPOP (inferredBy_Orthology). Malignant cells
motifmetacluster_141.24.490.0831E2F2; E2F3 (directAnnotation). 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.)



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."