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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: GSE150930

Dataset summary for GSE150930

Datast informationDatasetGSE150930
PMID33194728
Raw data ID/linkPRJNA634108
OrganismHomo sapiens
Sourcepatients
TissuePeripheral blood mononuclear cells
Cancer type level1Chronic lymphocytic leukemia
Cancer type level2Mucosa-assisted lymphoid tissue (MALT) lymphoma
Regimenrituximab + cyclophosphamide + fludarabine
Drug typeImmunotherapy
Sample sizeresistant 1, sensitive 1
Cell number2630
Extract protocol10x genomics
Data processingCellRanger
Public datePublic on Oct 27, 2020
DescriptionThis dataset has 1 patient with a sensitive pre-treatment sample and a resistant post-treatment sample.

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Drug summary for GSE150930

Drug nameDrugBank IDDrug typeTargets nameTargets uniprot ID
"Rituximab"

DB00073

biotechMS4A1P11836
"Cyclophosphamide"

DB00531

small moleculeNR1I2O75469
"Fludarabine"

DB01073

small moleculeDCK; POLA1; RRM1P27707; P09884; P23921

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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

RPS15A

ENSG000001344190.2706362.95e-234.67e-190.9980.995Malignant cellsNA

CTSH

ENSG000001038110.2698532.03e-153.20e-110.4450.284Malignant cellsNA

CD74

ENSG000000195820.2695543.03e-234.78e-190.9990.999Malignant cellsNA

ISCU

ENSG000001360030.2684861.29e-142.03e-100.6120.454Malignant cellsNA

LIMD2

ENSG000001364900.2637045.77e-139.12e-090.6830.55Malignant cellsNA

RPS29

ENSG000002137410.263081.33e-232.10e-190.9990.995Malignant cellsNA

RPL23A

ENSG000001982420.2593021.53e-262.42e-2211Malignant cellsNA

PRKCB

ENSG000001665010.2526191.45e-122.29e-080.5940.438Malignant cellsNA

TTN

ENSG000001556570.2526028.41e-101.33e-050.5470.414Malignant cellsNA

TLE1

ENSG000001967810.2508833.25e-145.13e-100.2920.152Malignant cellsNA

RPS15

ENSG000001152680.2501787.55e-211.19e-160.9991Malignant cellsNA

RPL14

ENSG00000188846-0.2575576.65e-181.05e-130.9550.984Malignant cellsNA

HERPUD1

ENSG00000051108-0.2589311.44e-092.27e-050.4540.571Malignant cellsNA

SCIMP

ENSG00000161929-0.2592162.95e-104.66e-060.3380.452Malignant cellsNA

ARHGAP9

ENSG00000123329-0.2595576.96e-141.10e-090.2230.364Malignant cellsNA

ATF5

ENSG00000169136-0.2600481.79e-102.83e-060.2090.331Malignant cellsNA

ARID5B

ENSG00000150347-0.2649717.64e-101.21e-050.6450.729Malignant cellsNA

RPL32

ENSG00000144713-0.2650271.60e-252.52e-210.9920.999Malignant cellsNA

ZNF292

ENSG00000188994-0.2673652.99e-114.72e-070.5680.664Malignant cellsNA

RHOH

ENSG00000168421-0.2731434.99e-137.88e-090.4630.6Malignant cellsNA

P4HA1

ENSG00000122884-0.2807052.41e-183.81e-140.2090.383Malignant cellsNA

SRGN

ENSG00000122862-0.2818631.68e-112.65e-070.6170.716Malignant cellsNA

PKM

ENSG00000067225-0.2820612.08e-113.29e-070.2890.417Malignant cellsNA

WNT3

ENSG00000277626-0.2878334.32e-136.82e-090.3980.539Malignant cellsNA

SLC2A3

ENSG00000059804-0.2889154.62e-167.29e-120.2390.409Malignant cellsNA

UBB

ENSG00000170315-0.2915097.96e-151.26e-100.6270.744Malignant cellsNA

HIST1H4C

NA-0.3038435.89e-149.30e-100.6440.739Malignant cellsNA

HLA-DQB1

ENSG00000206237-0.3068421.84e-172.90e-130.8630.932Malignant cellsNA

NR4A2

ENSG00000153234-0.3080311.71e-172.70e-130.3360.512Malignant cellsNA

MARCKSL1

ENSG00000175130-0.3101145.76e-179.09e-130.2620.428Malignant cellsNA

RPL21

ENSG00000122026-0.3118235.68e-278.98e-230.9820.995Malignant cellsNA

TSC22D3

ENSG00000157514-0.3226496.99e-151.10e-100.7160.804Malignant cellsNA

JUND

ENSG00000130522-0.3413133.87e-216.12e-170.920.96Malignant cellsNA

PGK1

ENSG00000102144-0.3749142.42e-143.82e-100.4320.559Malignant cellsNA

LDHA

ENSG00000288299-0.3799872.92e-194.62e-150.3940.561Malignant cellsNA

RNASET2

ENSG00000026297-0.382846.91e-161.09e-110.5460.669Malignant cellsNA

ZFP36L2

ENSG00000152518-0.396377.33e-201.16e-150.4130.589Malignant cellsNA

H3F3B

NA-0.3978582.03e-253.21e-210.9290.972Malignant cellsNA

HSP90AA1

ENSG00000080824-0.3989862.05e-153.24e-110.650.743Malignant cellsNA

NR4A1

ENSG00000123358-0.4172835.49e-278.68e-230.2160.436Malignant cellsNA

ENO1

ENSG00000074800-0.4220372.43e-223.83e-180.5160.686Malignant cellsNA

CD69

ENSG00000110848-0.42282.35e-173.71e-130.4720.625Malignant cellsNA

FOSB

ENSG00000125740-0.4258753.67e-215.80e-170.6430.779Malignant cellsNA

ID1

ENSG00000125968-0.4313721.22e-271.93e-230.1280.323Malignant cellsNA

RGCC

ENSG00000102760-0.4458792.94e-254.64e-210.2590.465Malignant cellsNA

TPI1

ENSG00000111669-0.4501111.60e-262.52e-220.4410.638Malignant cellsNA

RPL9P9

NA-0.4765869.03e-371.43e-320.4480.707Malignant cellsNA

BTG2

ENSG00000159388-0.4806031.44e-232.27e-190.6490.766Malignant cellsNA

BTG1

ENSG00000133639-0.4812151.21e-421.92e-380.9270.969Malignant cellsNA

JUN

ENSG00000177606-0.5075351.07e-281.69e-240.8210.912Malignant 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 Pathway1.20e-066.20e-061017811523467Malignant cellsCFLAR,ID1,JUN,PKM,S100A4,YWHAZ,BTG1,DUSP1,DUSP2,EGR1,ETS1,GAPDH,LDHA,PGK1,ENO1
Epigenetic Alteration of DNA, RNA or Protein8.60e-011.00e+00101455123467Malignant cellsGAPDH
Aberration of the Drug's Therapeutic Target1.00e+001.00e+0010190023467Malignant cells
Drug Inactivation by Structure Modification1.00e+001.00e+0010127023467Malignant cells
Irregularity in Drug Uptake and Drug Efflux1.00e+001.00e+0010137023467Malignant 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+002186023467CD4+ T cellsNA
Regulation by the Disease Microenvironment1.00e+001.00e+008186023467Mono_MacroNA

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
motifmetacluster_82.44.980.119ZFP30 (directAnnotation). Malignant cells
motiftransfac_pro__M063664.540.111ZNF530 (directAnnotation). Malignant cells
motifmetacluster_9.114.20.104GBX2 (directAnnotation). Malignant cells
motiftaipale_tf_pairs__TEAD4_SPIB_RGAATGCGGAAGTN_CAP_24.040.101SPIB; TEAD4 (directAnnotation). Malignant cells
motifmetacluster_12.13.840.0977ZNF3 (directAnnotation). Malignant cells
motifmetacluster_2.93.820.0972IRF2; IRF2; IRF2; PRDM1; PRDM1 (directAnnotation). PRDM1 (inferredBy_Orthology). Malignant cells
motiftaipale_tf_pairs__ERF_MAX_RSCGGAANCACGTGN_CAP_repr3.810.097ERF; MAX (directAnnotation). Malignant cells
motiftaipale_tf_pairs__ETV2_GSC2_RCCGGANNNNNNNNNTAATCCN_CAP_repr3.720.0954ETV2; GSC2 (directAnnotation). Malignant cells
motifjaspar__MA0693.33.70.095VDR (inferredBy_Orthology). Malignant cells
motifhdpi__KLF43.630.0936KLF4 (directAnnotation). Malignant cells
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Motifs and TFs regulating down-regulated DEGs in resistant group
motifmotifNESAUCTF_highConfCell_type
motiftfdimers__MD000518.440.529GABPA; STAT6 (directAnnotation). CD4+ T cells
motifswissregulon__hs__PAX28.30.52PAX2 (directAnnotation). CD4+ T cells
motiftransfac_pro__M058727.940.498ZNF655 (directAnnotation). CD4+ T cells
motifkznf__ZNF432_Imbeault2017_RP_RCADE7.790.489ZNF432 (directAnnotation). CD4+ T cells
motiftransfac_pro__M059317.740.486ZNF556 (directAnnotation). CD4+ T cells
motifhomer__YTKGATAHAGTATTCTWGGTNGGCA_ZNF1367.660.482ZNF136 (directAnnotation). CD4+ T cells
motifmetacluster_44.137.660.481NKX3-1; NKX3-2 (directAnnotation). CD4+ T cells
motiftaipale_tf_pairs__ELK1_FOXI1_RSCGGAANRTMAAYA_CAP_repr7.450.468ELK1; FOXI1 (directAnnotation). CD4+ T cells
motifjaspar__MA1962.17.420.467SOX2 (directAnnotation). CD4+ T cells
motiftfdimers__MD004727.420.467EP300; HOXA13 (directAnnotation). CD4+ T 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

IRF1

metacluster_2.7upMalignant cellsNA

STAT1

metacluster_2.7upMalignant cellsNA

IRF1

tfdimers__MD00527upMalignant cellsNA

NR4A1

hdpi__NR4A1downMalignant 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."