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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

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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

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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 (This dataset does not contain this module)

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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: GSE189460

Dataset summary for GSE189460

Datast informationDatasetGSE189460
PMID36380017
Raw data ID/linkPRJNA783047
OrganismHomo sapiens
Sourcepatients
TissueBone marrow aspirate
Cancer type level1Multiple myeloma
Cancer type level2Multiple myeloma (MM)
Regimenbortezomib + melphalan + prednisolone
Drug typeTargeted therapy
Sample sizepre (resistant 5, sensitive 13)
Cell number110638
Extract protocol10x genomics
Data processingCellRanger 3.0.1
Public datePublic on Sep 14, 2022
DescriptionThis dataset has 18 patients with pre-treatment samples.

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Drug summary for GSE189460

Drug nameDrugBank IDDrug typeTargets nameTargets uniprot ID
"Bortezomib"

DB00188

small moleculePSMB5; PSMB1P28074; P20618
"melphalan" is not included in the drug list.
"Prednisolone"

DB00860

small moleculeNR3C1P04150

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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.)

boxplot

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.)

resistant vs. sensitive

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

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.
Gene symbolGene idavg_log2FCp_valp_val_adjpct.1pct.2Cell typeTimepoint

MAP3K8

ENSG00000107968-0.2617191.99e-124.84e-080.2780.351CD8+ T cellspre

SERTAD1

ENSG00000197019-0.2619817.06e-191.72e-140.310.411CD8+ T cellspre

JOSD1

ENSG00000100221-0.2625513.79e-269.20e-220.1990.321CD8+ T cellspre

DNAJB1

ENSG00000132002-0.263877.04e-171.71e-120.5420.623CD8+ T cellspre

METRNL

ENSG00000275031-0.2657741.28e-193.10e-150.2640.367CD8+ T cellspre

BHLHE40

ENSG00000134107-0.2665342.73e-206.64e-160.2050.308CD8+ T cellspre

IDI1

ENSG00000067064-0.2668515.46e-161.33e-110.3920.476CD8+ T cellspre

RPL12

ENSG00000197958-0.2690990.00e+000.00e+0011CD8+ T cellspre

RPS15A

ENSG00000134419-0.2743930.00e+000.00e+0011CD8+ T cellspre

PPDPF

ENSG00000125534-0.2761339.65e-272.35e-220.5480.651CD8+ T cellspre

RPL37A

ENSG00000197756-0.2777720.00e+007.23e-4211CD8+ T cellspre

P2RY8

ENSG00000182162-0.2782572.27e-275.51e-230.1630.28CD8+ T cellspre

RPL9

ENSG00000163682-0.2809020.00e+000.00e+0011CD8+ T cellspre

RPL35A

ENSG00000182899-0.2819340.00e+000.00e+000.9991CD8+ T cellspre

KLF2

ENSG00000127528-0.2842176.69e-091.63e-040.9160.94CD8+ T cellspre

RPL14

ENSG00000188846-0.2869490.00e+000.00e+0011CD8+ T cellspre

CD69

ENSG00000110848-0.2891475.62e-221.37e-170.8480.904CD8+ T cellspre

FAM133B

ENSG00000234545-0.2918131.82e-224.43e-180.3860.491CD8+ T cellspre

CSRNP1

ENSG00000144655-0.2922145.21e-291.27e-240.2040.335CD8+ T cellspre

MIDN

ENSG00000167470-0.2937843.01e-187.32e-140.380.468CD8+ T cellspre

PDE4B

ENSG00000184588-0.2998698.84e-282.15e-230.2390.368CD8+ T cellspre

CD44

ENSG00000026508-0.3008812.91e-287.08e-240.630.723CD8+ T cellspre

LEPROTL1

ENSG00000104660-0.3021181.52e-323.70e-280.5670.681CD8+ T cellspre

IFNGR1

ENSG00000027697-0.3048297.21e-261.75e-210.1820.298CD8+ T cellspre

ZFP36L2

ENSG00000152518-0.3079611.40e-223.41e-180.9640.971CD8+ T cellspre

TCF7

ENSG00000081059-0.3121374.65e-311.13e-260.2690.404CD8+ T cellspre

RPL36A

ENSG00000241343-0.3136162.86e-256.94e-210.3140.43CD8+ T cellspre

ZFAS1

ENSG00000177410-0.3141545.22e-311.27e-260.5250.64CD8+ T cellspre

PIK3R1

ENSG00000145675-0.315142.04e-234.96e-190.650.728CD8+ T cellspre

IFRD1

ENSG00000006652-0.3172844.33e-121.05e-070.470.537CD8+ T cellspre

TENT5C

ENSG00000183508-0.3197823.24e-277.87e-230.3210.449CD8+ T cellspre

DNAJB6

ENSG00000105993-0.3220839.28e-332.25e-280.4410.573CD8+ T cellspre

STK17B

ENSG00000081320-0.3221139.04e-352.20e-300.5930.707CD8+ T cellspre

SBDS

ENSG00000126524-0.3277291.01e-302.47e-260.410.538CD8+ T cellspre

SARAF

ENSG00000133872-0.3278480.00e+000.00e+000.8740.935CD8+ T cellspre

PER1

ENSG00000179094-0.328522.77e-376.73e-330.1670.314CD8+ T cellspre

RPL37

ENSG00000145592-0.3310540.00e+000.00e+0011CD8+ T cellspre

REL

ENSG00000162924-0.3328631.31e-263.19e-220.3850.501CD8+ T cellspre

FOSL2

ENSG00000075426-0.3331667.70e-391.87e-340.1480.293CD8+ T cellspre

RPL32

ENSG00000144713-0.3339760.00e+000.00e+0011CD8+ T cellspre

SRGN

ENSG00000122862-0.3362967.35e-411.79e-360.9810.986CD8+ T cellspre

SRSF2

ENSG00000161547-0.3410314.62e-321.12e-270.7490.802CD8+ T cellspre

PDCD4

ENSG00000150593-0.3429414.51e-361.09e-310.5610.689CD8+ T cellspre

RPS28

ENSG00000233927-0.3453410.00e+000.00e+0011CD8+ T cellspre

TGFB1

ENSG00000105329-0.3514.61e-351.12e-300.5520.673CD8+ T cellspre

ITM2A

ENSG00000078596-0.3543675.99e-331.46e-280.4030.539CD8+ T cellspre

RPL34

ENSG00000109475-0.3549950.00e+000.00e+0011CD8+ T cellspre

RPS29

ENSG00000213741-0.3591850.00e+000.00e+0011CD8+ T cellspre

SELENOK

ENSG00000113811-0.3599461.51e-413.67e-370.6020.717CD8+ T cellspre

CTSW

ENSG00000172543-0.370780.00e+001.40e-450.3990.606CD8+ T cellspre
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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.

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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.)
Enrichment results for 5 known drug-resistant mechanisms in malignant cells
boxplot
MechnismPvalFDRSignatureGenesetOverlapBackgroundCell typeEnriched Genes
Unusual Activation of Pro-survival Pathway2.10e-171.10e-169457818623467Malignant cellsADAM10,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 Target1.50e-013.90e-0194590623467Malignant cellsBCL2,CDKN2A,EZH2,FGFR1,SF3B1,NPM1
Epigenetic Alteration of DNA, RNA or Protein3.80e-016.30e-019454552023467Malignant cellsBCL2L11,BCL2,DNMT1,FBXW7,H2AFY,LMNA,TYMS,PMAIP1,ARID4B,CDKN2A,CXCR4,EZH2,GAPDH,PDCD4,SMC4,TIMP1,CYTOR,MALAT1,PPP1R15A,MX1
Drug Inactivation by Structure Modification6.70e-017.80e-0194527123467Malignant cellsGSTP1
Irregularity in Drug Uptake and Drug Efflux7.80e-017.80e-0194537123467Malignant cellsSLC3A2

Enrichment results for 1 known drug resistance mechanisms in TME cells

boxplot
MechnismPvalFDRSignatureGenesetOverlapBackgroundCell typeEnriched Genes
Regulation by the Disease Microenvironment3.50e-013.50e-0154186123467B cellsRHOB
Regulation by the Disease Microenvironment1.00e+001.00e+0040186023467CD4+ T cellsNA
Regulation by the Disease Microenvironment1.90e-011.90e-01190186323467CD8+ T cellsTGFB1,CXCR4,TSPYL2
Regulation by the Disease Microenvironment1.00e+001.00e+0047186023467cDCsNA
Regulation by the Disease Microenvironment8.70e-018.70e-01255186123467ErythrocytesEZH2
Regulation by the Disease Microenvironment1.00e+001.00e+003186023467FibroblastsNA
Regulation by the Disease Microenvironment1.90e-021.90e-02194186523467Mono_MacroVEGFA,CX3CR1,IL1B,RHOB,VIM
Regulation by the Disease Microenvironment4.20e-014.20e-0168186123467NK cellsCXCR4
Regulation by the Disease Microenvironment1.00e+001.00e+0017186023467pDCsNA
Regulation by the Disease Microenvironment1.00e+001.00e+0022186023467ProgenitorsNA

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.)
Up-regulated HallmarkUp-regulated KEGGUp-regulated GO BP
boxplotboxplotboxplot

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.)
Down-regulated HallmarkDown-regulated KEGGDown-regulated GO BP
boxplotboxplotboxplot

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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.)

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.)

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.)

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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.)
Regulating up-regulated DEGs in resistant groupRegulating down-regulated DEGs in resistant group
boxplotboxplot

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.)

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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.)
Motifs and TFs regulating up-regulated DEGs in resistant group of the pre-treatment samples
motifmotifNESAUCTF_highConfCell_type
motifhdpi__TCEAL25.690.165TCEAL2 (directAnnotation). B cells
motiftransfac_pro__M012815.50.16ILF2; NFATC2 (directAnnotation). B cells
motiftransfac_pro__M035555.380.157ILF2; NFATC2 (directAnnotation). B cells
motiftransfac_pro__M063324.860.145ZNF585A (directAnnotation). B cells
motiftransfac_pro__M072844.840.144ERG (directAnnotation). B cells
motiftransfac_pro__M076084.770.143ILF2; NFAT5; NFATC1; NFATC2; NFATC4 (directAnnotation). B cells
motifmetacluster_5.24.750.142ZNF564 (directAnnotation). B cells
motiftransfac_pro__M073014.690.141NFATC4 (directAnnotation). B cells
motifhdpi__SCAND24.550.137SCAND2P (directAnnotation). B cells
motiftransfac_pro__M057794.380.133ZNF674 (directAnnotation). B cells
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Motifs and TFs regulating down-regulated DEGs in resistant group of the pre-treatment samples
motifmotifNESAUCTF_highConfCell_type
motiftaipale_tf_pairs__ETV2_RFX5_NACTTCCGGYNNNNGCAACSN_CAP_repr5.240.22ETV2; RFX5 (directAnnotation). B cells
motiftransfac_public__M002374.810.205AHR; ARNT (directAnnotation). B cells
motifjaspar__MA0033.24.440.192FOXL1 (directAnnotation). B cells
motiftaipale_tf_pairs__ELK1_TBX21_TNRCACCGGAAGNN_CAP_repr4.20.183ELK1; TBX21 (directAnnotation). B cells
motifmetacluster_16.64.150.181SOX1; SOX14; SOX15; SOX18; SOX2; SOX2; SOX8; SRY (directAnnotation). SOX1; SOX10; SOX17; SOX3 (inferredBy_Orthology). B cells
motiftransfac_pro__M060754.040.177ZNF197 (directAnnotation). B cells
motifswissregulon__hs__YY13.990.175YY1 (directAnnotation). B cells
motifmetacluster_112.13.990.175ZNF433 (directAnnotation). B cells
motiftaipale_tf_pairs__TEAD4_DLX2_NRCATTCNNNNYAATTN_CAP_repr3.860.171DLX2; TEAD4 (directAnnotation). B cells
motiftransfac_pro__M065433.80.169ZNF418 (directAnnotation). B cells
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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.)

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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

JUN

tfdimers__MD00036upB cellspre

FOXP1

metacluster_134.4downB cellspre

CREM

transfac_pro__M00801downCD8+ T cellspre

FOSL2

metacluster_157.2downcDCspre

FOSL2

transfac_pro__M03870downcDCspre

FOSL2

metacluster_137.2downcDCspre

HSF1

transfac_pro__M04761downErythrocytespre

HMGA1

tfdimers__MD00410downErythrocytespre

KLF10

metacluster_170.2upMalignant cellspre

KLF2

metacluster_170.2upMalignant cellspre
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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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