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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

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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: GSE164551

Dataset summary for GSE164551

Datast informationDatasetGSE164551
PMID33558511
Raw data ID/linkhttps://doi.org/10.7910/DVN/1RKYQ8
OrganismHomo sapiens
Sourcepatients
TissueBone marrow aspirate
Cancer type level1Multiple myeloma
Cancer type level2Refractory multiple myeloma (MM)
RegimenCAR-T
Drug typeImmunotherapy
Sample sizeresistant 1, sensitive 1
Cell number7736
Extract protocol10x genomics
Data processingCellRanger 3.1.0
Public datePublic on Jan 11, 2021
DescriptionThis dataset has 1 patient with a sensitive pre-treatment sample and a resistant post-treatment sample.

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Drug summary for GSE164551

Drug nameDrugBank IDDrug typeTargets nameTargets uniprot ID
"CAR-T" 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.)

resistant vs. sensitive

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Dot plot of significant ligand-receptor pairs in the resistant groupDot plot of significant ligand-receptor pairs in the sensitive group
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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

S100A8

ENSG00000143546-1.611090.00e+000.00e+000.8090.949Mono/MacroNA

ANXA1

ENSG00000135046-1.654830.00e+000.00e+000.610.935Mono/MacroNA

IER3

ENSG00000235030-1.853680.00e+000.00e+000.3360.892Mono/MacroNA

THBD

ENSG00000178726-1.857890.00e+000.00e+000.1640.821Mono/MacroNA

HMOX1

ENSG00000100292-2.247050.00e+000.00e+000.5280.909Mono/MacroNA

YJU2

ENSG00000105248-0.3037819.50e-071.50e-020.0130.25Malignant cellsNA

CXCL8

ENSG00000169429-0.3037816.14e-089.67e-040.0090.25Malignant cellsNA

GPRC5A

ENSG00000013588-0.3219286.23e-199.82e-1500.25Malignant cellsNA

GBP1

ENSG00000117228-0.5533531.02e-081.60e-040.0220.375Malignant cellsNA

IER5L

ENSG00000188483-0.5533531.19e-101.88e-060.0160.375Malignant cellsNA

LAPTM5

ENSG00000162511-0.7491924.56e-097.19e-050.0410.5Malignant cellsNA

SAT1

ENSG00000130066-0.915517.69e-071.21e-020.0920.625Malignant cellsNA

S100A9

ENSG00000163220-1.024231.99e-093.14e-050.0630.625Malignant cellsNA

CCL4L2

ENSG00000282604-1.107385.56e-088.76e-040.0090.25Malignant cellsNA

AC007952.4

NA-1.138083.06e-064.82e-020.070.5Malignant cellsNA

EGR1

ENSG00000120738-1.151788.04e-071.27e-020.0130.25Malignant cellsNA

CITED2

ENSG00000164442-1.594831.94e-073.05e-030.0510.5Malignant cellsNA

HBG2

ENSG000001965652.441227.95e-401.25e-350.490.213ErythrocytesNA

IGLC3

ENSG000002116790.9159530.00e+000.00e+000.3460.004ErythrocytesNA

HBA2

ENSG000001885360.8158650.00e+000.00e+000.9950.933ErythrocytesNA

BPGM

ENSG000001723310.7197530.00e+002.80e-440.8010.449ErythrocytesNA

KRT1

ENSG000001677680.6870890.00e+000.00e+000.5390.178ErythrocytesNA

HBA1

ENSG000002061720.6290850.00e+000.00e+000.9970.955ErythrocytesNA

GABARAPL2

ENSG000000347130.6008270.00e+002.80e-450.7790.443ErythrocytesNA

HBG1

ENSG000002139340.5465183.63e-285.73e-240.3020.092ErythrocytesNA

HBB

ENSG000002447340.5436141.79e-432.83e-390.9970.973ErythrocytesNA

GSPT1

ENSG000001033420.4753111.85e-252.92e-210.6260.395ErythrocytesNA

SNCA

ENSG000001453350.4624931.66e-302.61e-260.9260.762ErythrocytesNA

DCAF12

ENSG000001988760.4488291.88e-242.96e-200.6210.36ErythrocytesNA

FKBP8

ENSG000001057010.3690118.33e-281.31e-230.8970.682ErythrocytesNA

ADIPOR1

ENSG000001593460.3643967.61e-281.20e-230.7470.44ErythrocytesNA

ALAS2

ENSG000001585780.3618679.68e-201.53e-150.9440.835ErythrocytesNA

BNIP3L

ENSG000001047650.3477516.71e-181.06e-130.90.64ErythrocytesNA

STRADB

ENSG000000821460.3443879.77e-241.54e-190.6360.38ErythrocytesNA

RAP1GAP

ENSG000000768640.2992561.14e-281.79e-240.3550.125ErythrocytesNA

RNF10

ENSG000000228400.2895896.48e-181.02e-130.690.443ErythrocytesNA

OAZ1

ENSG000001049040.2850591.84e-142.89e-100.8120.687ErythrocytesNA

LYL1

ENSG000001049030.2823361.25e-161.97e-120.430.23ErythrocytesNA

GMPR

ENSG000001371980.2794883.37e-185.31e-140.5130.301ErythrocytesNA

BCL2L1

ENSG000001715520.27193.33e-135.24e-090.730.528ErythrocytesNA

KLF3

ENSG00000109787-0.2503582.76e-124.35e-080.3840.578ErythrocytesNA

EP300

ENSG00000100393-0.2505157.60e-081.20e-030.3820.524ErythrocytesNA

MYL6

ENSG00000092841-0.2508731.92e-073.02e-030.7030.75ErythrocytesNA

TMEM56

NA-0.2513651.19e-081.88e-040.2290.354ErythrocytesNA

GOLGA4

ENSG00000144674-0.2524371.38e-072.17e-030.2090.323ErythrocytesNA

NARF

ENSG00000141562-0.2527663.22e-115.08e-070.3420.506ErythrocytesNA

KIAA1551

NA-0.2541911.90e-093.00e-050.1340.25ErythrocytesNA

XPO7

ENSG00000130227-0.2564159.99e-101.57e-050.2680.415ErythrocytesNA

NDUFA2

ENSG00000131495-0.256451.77e-142.78e-100.1140.271ErythrocytesNA

TRAK2

ENSG00000115993-0.2565076.48e-091.02e-040.2790.414ErythrocytesNA
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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 Pathway5.90e-022.90e-0112781223467Malignant cellsEGR1,CXCL8
Epigenetic Alteration of DNA, RNA or Protein2.10e-015.20e-0112455123467Malignant cellsCXCL8
Aberration of the Drug's Therapeutic Target1.00e+001.00e+001290023467Malignant cells
Drug Inactivation by Structure Modification1.00e+001.00e+001227023467Malignant cells
Irregularity in Drug Uptake and Drug Efflux1.00e+001.00e+001237023467Malignant cells

Enrichment results for 1 known drug resistance mechanisms in TME cells

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MechnismPvalFDRSignatureGenesetOverlapBackgroundCell typeEnriched Genes
Regulation by the Disease Microenvironment1.00e+001.00e+003186023467B cellsNA
Regulation by the Disease Microenvironment6.60e-036.60e-03148186523467CD4+ T cellsBRAF,TGFB1,SOCS3,VIM,ZEB1
Regulation by the Disease Microenvironment1.80e-011.80e-01276186423467CD8+ T cellsNFKB1,TGFB1,CXCR4,VIM
Regulation by the Disease Microenvironment5.10e-015.10e-01467186423467ErythrocytesBCL2L1,MTDH,HNRNPA2B1,MALAT1
Regulation by the Disease Microenvironment9.20e-039.20e-035241861023467Mono_MacroBRAF,CTNNB1,TGFB1,VEGFA,ZEB2,IL1B,HNRNPA2B1,SOCS3,VIM,MALAT1
Regulation by the Disease Microenvironment4.80e-014.80e-0181186123467NK cellsVIM

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
This dataset does not contain malignant cells, nor does it predict any miRNA that corresponds to the top10 DEGs.boxplot

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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__M028484.050.193EGR1 (inferredBy_Orthology). CD4+ T cells
motiftaipale_tf_pairs__ETV5_HES7_NNCACGTGNNNNCCGGAANN_CAP4.020.192ETV5; HES7 (directAnnotation). CD4+ T cells
motiftransfac_pro__M074753.810.185TBX5 (inferredBy_Orthology). CD4+ T cells
motifcisbp__M007753.790.184ZBTB1 (inferredBy_Orthology). CD4+ T cells
motifmetacluster_84.23.760.183RARA (directAnnotation). CD4+ T cells
motiftaipale_tf_pairs__E2F1_ELK1_SGCGCNNNNNNNNNNCGGAAGN_CAP_repr3.740.182E2F1; ELK1 (directAnnotation). CD4+ T cells
motifmetacluster_141.53.710.181NR3C1; THAP1; YY1; YY1; YY1; YY1; YY1; YY1; YY1; YY1; YY1; YY1; YY1; YY1; YY2; YY2; ZNF597 (directAnnotation). YY1; YY1; YY1; YY2; ZFP42 (inferredBy_Orthology). CD4+ T cells
motifjaspar__MA1650.13.680.18ZBTB14 (directAnnotation). CD4+ T cells
motiftransfac_pro__M020903.620.178E2F4 (directAnnotation). CD4+ T cells
motiftransfac_pro__M080053.560.176TCFL5 (inferredBy_Orthology). CD4+ T cells
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Motifs and TFs regulating down-regulated DEGs in resistant group
motifmotifNESAUCTF_highConfCell_type
motiftransfac_pro__M012527.710.61E2F6 (directAnnotation). B cells
motiftfdimers__MD003107.020.558IKZF1; OTX1; OTX2 (directAnnotation). B cells
motifmetacluster_76.16.650.53ZNF345; ZNF345 (directAnnotation). MYB; MYBL1 (inferredBy_Orthology). B cells
motifmetacluster_156.26.560.523ATF3; ATF4; ATF4; ATF4; ATF4; ATF4; ATF4; CEBPG; CEBPG; DDIT3; MYC (directAnnotation). ATF4; ATF4; ATF4; CEBPG; DDIT3 (inferredBy_Orthology). B cells
motiftransfac_pro__M055316.50.518IKZF5 (inferredBy_Orthology). B cells
motiftfdimers__MD001036.440.514ZNF333 (directAnnotation). B cells
motifcisbp__M008386.020.482FOXP1 (directAnnotation). B cells
motifmetacluster_130.15.990.48ZNF713; ZNF713 (directAnnotation). HSF1; HSF2; HSF4; HSF5; HSFX1; HSFX2; HSFX3; HSFX4; HSFY1; HSFY2 (inferredBy_Orthology). B cells
motifmetacluster_139.95.890.473TFE3 (inferredBy_Orthology). B cells
motiftfdimers__MD002985.880.471CEBPA; CEBPB; CEBPD; CEBPE; CEBPG; FOXL1 (directAnnotation). B 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

ZEB1

tfdimers__MD00527upCD4+ T cellsNA

MECP2

metacluster_135.10upCD8+ T cellsNA

E2F4

metacluster_45.6downErythrocytesNA

KLF13

hocomoco__KLF13_HUMAN.H11MO.0.DdownErythrocytesNA

YBX1

metacluster_79.33downErythrocytesNA

BACH1

metacluster_22.37upMono/MacroNA

BACH1

metacluster_157.2upMono/MacroNA

BACH1

metacluster_30.4upMono/MacroNA

EGR1

cisbp__M01864upMono/MacroNA

EGR1

metacluster_131.7upMono/MacroNA
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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."