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Dataset: GSE189460 |
Dataset summary for GSE189460 |
Datast information | Dataset | GSE189460 |
PMID | 36380017 | |
Raw data ID/link | PRJNA783047 | |
Organism | Homo sapiens | |
Source | patients | |
Tissue | Bone marrow aspirate | |
Cancer type level1 | Multiple myeloma | |
Cancer type level2 | Multiple myeloma (MM) | |
Regimen | bortezomib + melphalan + prednisolone | |
Drug type | Targeted therapy | |
Sample size | pre (resistant 5, sensitive 13) | |
Cell number | 110638 | |
Extract protocol | 10x genomics | |
Data processing | CellRanger 3.0.1 | |
Public date | Public on Sep 14, 2022 | |
Description | This dataset has 18 patients with pre-treatment samples. |
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Drug summary for GSE189460 |
Drug name | DrugBank ID | Drug type | Targets name | Targets uniprot ID |
"Bortezomib" | DB00188 | small molecule | PSMB5; PSMB1 | P28074; P20618 |
"melphalan" is not included in the drug list. | ||||
"Prednisolone" | DB00860 | small molecule | NR3C1 | P04150 |
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Umap of single cell types and conditions (resistant and sensitive) |
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Umap of cell types![]() | Umap of conditions![]() |
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Comparison of cell composition between the resistant and sensitive groups |
![]() * represents significant difference. (If the image exists, the user can click on it to enlarge it in a new window.) |
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![]() * 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 |
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Comparison of ITH scores![]() | Comparison of EMT scores![]() |
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Difference of cell-cell interactions between the resistant and sensitive groups |
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resistant vs. sensitive ![]() |
Dot plot of significant ligand-receptor pairs in the resistant group | Dot 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 |
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Gene symbol | Gene id | avg_log2FC | p_val | p_val_adj | pct.1 | pct.2 | Cell type | Timepoint |
H2AFV | NA | 0.926504 | 0.00e+00 | 0.00e+00 | 0.659 | 0.318 | Malignant cells | pre |
BTG1 | ENSG00000133639 | 0.925506 | 0.00e+00 | 0.00e+00 | 0.906 | 0.645 | Malignant cells | pre |
H1FX | NA | 0.924163 | 0.00e+00 | 0.00e+00 | 0.911 | 0.751 | Malignant cells | pre |
CD53 | ENSG00000143119 | 0.923663 | 0.00e+00 | 0.00e+00 | 0.826 | 0.544 | Malignant cells | pre |
RAB11FIP1 | ENSG00000156675 | 0.923217 | 0.00e+00 | 0.00e+00 | 0.674 | 0.316 | Malignant cells | pre |
DUSP1 | ENSG00000120129 | 0.91493 | 0.00e+00 | 0.00e+00 | 0.926 | 0.796 | Malignant cells | pre |
ANP32B | ENSG00000136938 | 0.909592 | 0.00e+00 | 0.00e+00 | 0.764 | 0.546 | Malignant cells | pre |
PIM1 | ENSG00000137193 | 0.907029 | 0.00e+00 | 0.00e+00 | 0.594 | 0.196 | Malignant cells | pre |
JUNB | ENSG00000171223 | 0.905235 | 0.00e+00 | 0.00e+00 | 0.923 | 0.685 | Malignant cells | pre |
HSP90AB1 | ENSG00000096384 | 0.899596 | 0.00e+00 | 0.00e+00 | 0.976 | 0.844 | Malignant cells | pre |
LGALS1 | ENSG00000100097 | 0.894493 | 0.00e+00 | 0.00e+00 | 0.748 | 0.622 | Malignant cells | pre |
NCL | ENSG00000115053 | 0.885605 | 0.00e+00 | 0.00e+00 | 0.885 | 0.631 | Malignant cells | pre |
ARID5B | ENSG00000150347 | 0.866521 | 0.00e+00 | 0.00e+00 | 0.586 | 0.276 | Malignant cells | pre |
DUSP2 | ENSG00000158050 | 0.856415 | 0.00e+00 | 0.00e+00 | 0.407 | 0.239 | Malignant cells | pre |
VAPA | ENSG00000101558 | 0.851441 | 0.00e+00 | 0.00e+00 | 0.683 | 0.323 | Malignant cells | pre |
SRSF7 | ENSG00000115875 | 0.84872 | 0.00e+00 | 0.00e+00 | 0.777 | 0.492 | Malignant cells | pre |
FKBP5 | ENSG00000096060 | 0.832279 | 0.00e+00 | 0.00e+00 | 0.406 | 0.081 | Malignant cells | pre |
IRF2BP2 | ENSG00000168264 | 0.830731 | 0.00e+00 | 0.00e+00 | 0.625 | 0.284 | Malignant cells | pre |
FTL | ENSG00000087086 | 0.827193 | 0.00e+00 | 0.00e+00 | 0.999 | 0.997 | Malignant cells | pre |
BCAP31 | ENSG00000185825 | 0.823809 | 0.00e+00 | 0.00e+00 | 0.765 | 0.401 | Malignant cells | pre |
GUK1 | ENSG00000143774 | 0.811626 | 0.00e+00 | 0.00e+00 | 0.925 | 0.761 | Malignant cells | pre |
NR4A2 | ENSG00000153234 | 0.809825 | 0.00e+00 | 0.00e+00 | 0.433 | 0.195 | Malignant cells | pre |
EPRS | NA | 0.809688 | 0.00e+00 | 0.00e+00 | 0.644 | 0.4 | Malignant cells | pre |
C12orf57 | ENSG00000111678 | 0.803119 | 0.00e+00 | 0.00e+00 | 0.86 | 0.547 | Malignant cells | pre |
SRSF3 | ENSG00000112081 | 0.779768 | 0.00e+00 | 0.00e+00 | 0.804 | 0.633 | Malignant cells | pre |
FUS | ENSG00000089280 | 0.774572 | 0.00e+00 | 0.00e+00 | 0.673 | 0.373 | Malignant cells | pre |
BIRC3 | ENSG00000023445 | 0.770117 | 0.00e+00 | 0.00e+00 | 0.322 | 0.203 | Malignant cells | pre |
RPS20 | ENSG00000008988 | 0.765981 | 0.00e+00 | 0.00e+00 | 0.967 | 0.726 | Malignant cells | pre |
PARP1 | ENSG00000143799 | 0.76448 | 0.00e+00 | 0.00e+00 | 0.732 | 0.38 | Malignant cells | pre |
FOS | ENSG00000170345 | 0.762859 | 0.00e+00 | 0.00e+00 | 0.929 | 0.78 | Malignant cells | pre |
FUNDC2 | ENSG00000165775 | 0.757766 | 0.00e+00 | 0.00e+00 | 0.637 | 0.293 | Malignant cells | pre |
ARF1 | ENSG00000143761 | 0.757446 | 0.00e+00 | 0.00e+00 | 0.927 | 0.73 | Malignant cells | pre |
RTF2 | ENSG00000022277 | 0.755232 | 0.00e+00 | 0.00e+00 | 0.429 | 0.191 | Malignant cells | pre |
HNRNPAB | ENSG00000197451 | 0.754511 | 0.00e+00 | 0.00e+00 | 0.605 | 0.27 | Malignant cells | pre |
PTMA | ENSG00000187514 | 0.748795 | 0.00e+00 | 0.00e+00 | 0.998 | 0.991 | Malignant cells | pre |
HNRNPA3 | ENSG00000170144 | 0.744621 | 0.00e+00 | 0.00e+00 | 0.849 | 0.622 | Malignant cells | pre |
NENF | ENSG00000117691 | 0.739691 | 0.00e+00 | 0.00e+00 | 0.711 | 0.431 | Malignant cells | pre |
CUTA | ENSG00000226492 | 0.739002 | 0.00e+00 | 0.00e+00 | 0.934 | 0.852 | Malignant cells | pre |
IER5 | ENSG00000162783 | 0.738007 | 0.00e+00 | 0.00e+00 | 0.679 | 0.302 | Malignant cells | pre |
UBC | ENSG00000150991 | 0.736658 | 0.00e+00 | 0.00e+00 | 0.998 | 0.987 | Malignant cells | pre |
SERF2 | ENSG00000140264 | 0.73558 | 0.00e+00 | 0.00e+00 | 0.998 | 0.993 | Malignant cells | pre |
NUCKS1 | ENSG00000069275 | 0.732891 | 0.00e+00 | 0.00e+00 | 0.605 | 0.279 | Malignant cells | pre |
HNRNPA2B1 | ENSG00000122566 | 0.72751 | 0.00e+00 | 0.00e+00 | 0.965 | 0.867 | Malignant cells | pre |
MIR4435-2HG | ENSG00000172965 | 0.727259 | 0.00e+00 | 0.00e+00 | 0.487 | 0.101 | Malignant cells | pre |
DUT | ENSG00000128951 | 0.72389 | 0.00e+00 | 0.00e+00 | 0.633 | 0.398 | Malignant cells | pre |
NDUFV2 | ENSG00000178127 | 0.721395 | 0.00e+00 | 0.00e+00 | 0.721 | 0.5 | Malignant cells | pre |
TUBB4B | ENSG00000188229 | 0.715699 | 0.00e+00 | 0.00e+00 | 0.644 | 0.385 | Malignant cells | pre |
SRP9 | ENSG00000143742 | 0.711245 | 0.00e+00 | 0.00e+00 | 0.756 | 0.492 | Malignant cells | pre |
H2AFY | NA | 0.706338 | 0.00e+00 | 0.00e+00 | 0.469 | 0.187 | Malignant cells | pre |
MDH1 | ENSG00000014641 | 0.705636 | 0.00e+00 | 0.00e+00 | 0.691 | 0.408 | Malignant cells | pre |
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Mechanism analysis of drug resistance-related DEGs for each cell type in the pre-treatment samples |
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Enrichment results for 5 known drug-resistant mechanisms in malignant cells |
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Mechnism | Pval | FDR | Signature | Geneset | Overlap | Background | Cell type | Enriched Genes |
Unusual Activation of Pro-survival Pathway | 2.10e-17 | 1.10e-16 | 945 | 781 | 86 | 23467 | Malignant cells | ADAM10,AREG,BCL2L11,BAX,BCL2,CDKN1A,CDKN1B,DNMT1,FBXW7,GSTP1,HMGB1,ID1,EIF4G1,IFI27,JUN,PKM,MCL1,MAP1LC3B,MYC,PARP1,PTEN,KRAS,RALBP1,RHOA,S100A4,STMN1,TP53INP1,TPD52,TYMS,YWHAZ,SLC25A5,ANXA1,HSPA5,BTG1,CASP8,CCND1,CDKN2A,HSPD1,CXCR4,DDIT3,DUSP1,DUSP2,EGR1,EZH2,EZR,FGFR1,FTL,FUS,GAPDH,NR3C1,GRB2,HMGB2,HNRNPU,HSPA8,EIF4A1,NFKBIA,ITGB1,TCF4,MAP4K3,MDM4,NSD2,NUCKS1,PABPC1,PDCD4,PRKDC,PTPN18,RAC1,RAP1B,RND3,HNRNPA1,SFPQ,SMC4,SMARCC1,SRSF2,TNFAIP3,TOP1,UCP2,WEE1,YBX1,GNAS,NPM1,BRD2,G3BP1,PMVK,QPRT,HSH2D |
Aberration of the Drug's Therapeutic Target | 1.50e-01 | 3.90e-01 | 945 | 90 | 6 | 23467 | Malignant cells | BCL2,CDKN2A,EZH2,FGFR1,SF3B1,NPM1 |
Epigenetic Alteration of DNA, RNA or Protein | 3.80e-01 | 6.30e-01 | 945 | 455 | 20 | 23467 | Malignant cells | BCL2L11,BCL2,DNMT1,FBXW7,H2AFY,LMNA,TYMS,PMAIP1,ARID4B,CDKN2A,CXCR4,EZH2,GAPDH,PDCD4,SMC4,TIMP1,CYTOR,MALAT1,PPP1R15A,MX1 |
Drug Inactivation by Structure Modification | 6.70e-01 | 7.80e-01 | 945 | 27 | 1 | 23467 | Malignant cells | GSTP1 |
Irregularity in Drug Uptake and Drug Efflux | 7.80e-01 | 7.80e-01 | 945 | 37 | 1 | 23467 | Malignant cells | SLC3A2 |
Enrichment results for 1 known drug resistance mechanisms in TME cells |
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Mechnism | Pval | FDR | Signature | Geneset | Overlap | Background | Cell type | Enriched Genes |
Regulation by the Disease Microenvironment | 3.50e-01 | 3.50e-01 | 54 | 186 | 1 | 23467 | B cells | RHOB |
Regulation by the Disease Microenvironment | 1.00e+00 | 1.00e+00 | 40 | 186 | 0 | 23467 | CD4+ T cells | NA |
Regulation by the Disease Microenvironment | 1.90e-01 | 1.90e-01 | 190 | 186 | 3 | 23467 | CD8+ T cells | TGFB1,CXCR4,TSPYL2 |
Regulation by the Disease Microenvironment | 1.00e+00 | 1.00e+00 | 47 | 186 | 0 | 23467 | cDCs | NA |
Regulation by the Disease Microenvironment | 8.70e-01 | 8.70e-01 | 255 | 186 | 1 | 23467 | Erythrocytes | EZH2 |
Regulation by the Disease Microenvironment | 1.00e+00 | 1.00e+00 | 3 | 186 | 0 | 23467 | Fibroblasts | NA |
Regulation by the Disease Microenvironment | 1.90e-02 | 1.90e-02 | 194 | 186 | 5 | 23467 | Mono_Macro | VEGFA,CX3CR1,IL1B,RHOB,VIM |
Regulation by the Disease Microenvironment | 4.20e-01 | 4.20e-01 | 68 | 186 | 1 | 23467 | NK cells | CXCR4 |
Regulation by the Disease Microenvironment | 1.00e+00 | 1.00e+00 | 17 | 186 | 0 | 23467 | pDCs | NA |
Regulation by the Disease Microenvironment | 1.00e+00 | 1.00e+00 | 22 | 186 | 0 | 23467 | Progenitors | NA |
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Up-regulated Hallmark | Up-regulated KEGG | Up-regulated GO BP |
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Down-regulated Hallmark | Down-regulated KEGG | Down-regulated GO BP |
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Mechanism analysis of drug resistance-related DEGs for each cell type in the post-treatment samples |
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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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Regulating up-regulated DEGs in resistant group | Regulating down-regulated DEGs in resistant group |
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Motifs and transcription factors (TFs) regulating drug resistance-related DEGs for each cell type |
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Motifs and TFs regulating up-regulated DEGs in resistant group of the pre-treatment samples |
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Motifs and TFs regulating down-regulated DEGs in resistant group of the pre-treatment samples |
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Differentially expressed genes act as transcription factors |
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TF | motif | Expression | Cell type | Timepoint |
JUN | tfdimers__MD00036 | up | B cells | pre |
FOXP1 | metacluster_134.4 | down | B cells | pre |
CREM | transfac_pro__M00801 | down | CD8+ T cells | pre |
FOSL2 | metacluster_157.2 | down | cDCs | pre |
FOSL2 | transfac_pro__M03870 | down | cDCs | pre |
FOSL2 | metacluster_137.2 | down | cDCs | pre |
HSF1 | transfac_pro__M04761 | down | Erythrocytes | pre |
HMGA1 | tfdimers__MD00410 | down | Erythrocytes | pre |
KLF10 | metacluster_170.2 | up | Malignant cells | pre |
KLF2 | metacluster_170.2 | up | Malignant cells | pre |
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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." |
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