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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 (This dataset does not contain this module)

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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

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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: PMID34715028

Dataset summary for PMID34715028

Datast informationDatasetPMID34715028
PMID34715028
Raw data ID/linkEGAD00001008166
OrganismHomo sapiens
Sourcepatients
TissueTumor tissue
Cancer type level1Kidney cancer
Cancer type level2Clear cell renal cell carcinoma (ccRCC)
Regimennivolumab
Drug typeImmunotherapy
Sample sizepost (resistant 1, sensitive 1)
Cell number27332
Extract protocol10x genomics
Data processingCellRanger 5.0.0
Public datePublic on Oct 28, 2021
DescriptionThis dataset has 2 patients with post-treatment samples.

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Drug summary for PMID34715028

Drug nameDrugBank IDDrug typeTargets nameTargets uniprot ID
"Nivolumab"

DB09035

biotechPDCD1; CD274Q15116; Q9NZQ7

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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.)

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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.)

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 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.
Gene symbolGene idavg_log2FCp_valp_val_adjpct.1pct.2Cell typeTimepoint

HERPUD1

ENSG00000051108-0.3321455.54e-319.71e-270.2610.427CD4+ T cellspost

LDLRAD4

ENSG00000168675-0.3324291.48e-232.60e-190.2170.357CD4+ T cellspost

MAP1LC3B

ENSG00000140941-0.3333997.07e-361.24e-310.2950.481CD4+ T cellspost

CCNH

ENSG00000134480-0.3351161.58e-322.77e-280.3910.572CD4+ T cellspost

ARID5B

ENSG00000150347-0.3364033.10e-285.43e-240.4350.601CD4+ T cellspost

TRAF1

ENSG00000056558-0.3374242.14e-293.75e-250.2970.464CD4+ T cellspost

TAPBP

ENSG00000206281-0.3391252.21e-313.88e-270.4650.634CD4+ T cellspost

SNHG15

ENSG00000232956-0.3392330.00e+000.00e+000.1490.361CD4+ T cellspost

GPR132

ENSG00000183484-0.3423720.00e+000.00e+000.1050.312CD4+ T cellspost

MTHFD2

ENSG00000065911-0.3425690.00e+000.00e+000.1250.323CD4+ T cellspost

PDIA3

ENSG00000167004-0.3448386.21e-341.09e-290.4970.67CD4+ T cellspost

HLA-DPB1

ENSG00000236693-0.3471771.42e-302.49e-260.450.639CD4+ T cellspost

DDX21

ENSG00000165732-0.3499642.97e-415.20e-370.2540.455CD4+ T cellspost

B2M

ENSG00000273686-0.3503870.00e+000.00e+0011CD4+ T cellspost

FRMD4B

ENSG00000114541-0.3529562.54e-384.45e-340.1360.303CD4+ T cellspost

HAUS3

ENSG00000214367-0.3534360.00e+000.00e+000.0860.301CD4+ T cellspost

H2AFZ

NA-0.3546321.92e-293.37e-250.3780.542CD4+ T cellspost

PTPN22

ENSG00000134242-0.3559712.22e-223.90e-180.3080.44CD4+ T cellspost

GTF2B

ENSG00000137947-0.3567410.00e+000.00e+000.1360.342CD4+ T cellspost

SERTAD1

ENSG00000197019-0.3591630.00e+000.00e+000.050.277CD4+ T cellspost

CD7

ENSG00000173762-0.3608691.05e-201.84e-160.6150.71CD4+ T cellspost

KPNA2

ENSG00000182481-0.3610.00e+000.00e+000.0480.279CD4+ T cellspost

CKS2

ENSG00000123975-0.3623060.00e+000.00e+000.0770.288CD4+ T cellspost

PGK1

ENSG00000102144-0.3654663.21e-405.62e-360.4510.643CD4+ T cellspost

SIAH2

ENSG00000181788-0.3679850.00e+000.00e+000.1270.35CD4+ T cellspost

ATP2B1

ENSG00000070961-0.3688290.00e+000.00e+000.1450.348CD4+ T cellspost

ARF4

ENSG00000168374-0.3692610.00e+000.00e+000.2220.453CD4+ T cellspost

TRPS1

ENSG00000104447-0.3697550.00e+002.66e-430.120.307CD4+ T cellspost

EIF4A3

ENSG00000141543-0.3709520.00e+008.41e-450.1840.395CD4+ T cellspost

CHMP1B

ENSG00000255112-0.3718020.00e+000.00e+000.0920.291CD4+ T cellspost

RORA

ENSG00000069667-0.372511.07e-351.88e-310.4050.597CD4+ T cellspost

HLA-DRA

ENSG00000277263-0.3732931.06e-251.85e-210.2140.372CD4+ T cellspost

DNAJB9

ENSG00000128590-0.3748190.00e+000.00e+000.080.314CD4+ T cellspost

CD28

ENSG00000178562-0.3754393.18e-435.57e-390.2830.493CD4+ T cellspost

HNRNPA0

ENSG00000177733-0.3755461.12e-441.88e-400.4180.61CD4+ T cellspost

ETV6

ENSG00000139083-0.3763290.00e+000.00e+000.1880.404CD4+ T cellspost

CDC14A

ENSG00000079335-0.3784445.57e-419.76e-370.2340.431CD4+ T cellspost

ISG20

ENSG00000172183-0.3785021.84e-353.22e-310.4730.649CD4+ T cellspost

RHBDD2

ENSG00000005486-0.379533.67e-366.43e-320.2360.412CD4+ T cellspost

IER5

ENSG00000162783-0.3822620.00e+000.00e+000.1670.387CD4+ T cellspost

HIST1H4C

NA-0.3825132.23e-313.91e-270.3330.495CD4+ T cellspost

GABARAPL1

ENSG00000139112-0.3828550.00e+000.00e+000.1060.322CD4+ T cellspost

PPP2R5C

ENSG00000078304-0.3830472.84e-424.97e-380.3280.53CD4+ T cellspost

CDK17

ENSG00000059758-0.3845560.00e+004.20e-450.2270.443CD4+ T cellspost

HIST1H1C

NA-0.3852391.47e-342.58e-300.2850.464CD4+ T cellspost

GZMA

ENSG00000145649-0.3863881.01e-351.78e-310.1570.332CD4+ T cellspost

COTL1

ENSG00000103187-0.3866051.21e-382.12e-340.6350.81CD4+ T cellspost

LY6E

ENSG00000278032-0.3884428.97e-291.57e-240.4850.63CD4+ T cellspost

CALM2

ENSG00000143933-0.3898581.40e-453.07e-410.5610.748CD4+ T cellspost

S100A10

ENSG00000197747-0.3901973.22e-215.64e-170.6340.723CD4+ T cellspost
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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.)

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.)
Enrichment results for 1 known drug resistance mechanisms in TME cells

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MechnismPvalFDRSignatureGenesetOverlapBackgroundCell typeEnriched Genes
Regulation by the Disease Microenvironment8.40e-038.40e-035171861023467CD4+ T cellsBCL2,CDKN1B,NFKB1,TGFB1,CXCR4,FYN,SOCS3,STAT3,VIM,TSPYL2
Regulation by the Disease Microenvironment4.80e-054.80e-055001861423467CD8+ T cellsBCL2,CDKN1B,NFKB1,TGFB1,TGFBR2,CXCR4,FYN,GATA3,RHOB,HNRNPA2B1,SOCS3,STAT3,VIM,TSPYL2

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

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.)
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 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.)

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

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.)

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.)
Motifs and TFs regulating up-regulated DEGs in resistant group of the post-treatment samples
motifmotifNESAUCTF_highConfCell_type
motifswissregulon__hs__GMEB24.760.091GMEB2 (directAnnotation). CD4+ T cells
motiftransfac_pro__M064083.910.0802ZSCAN30 (directAnnotation). CD4+ T cells
motifswissregulon__hs__ETV63.850.0794ETV6 (directAnnotation). CD4+ T cells
motiftransfac_pro__M006553.780.0785ETV4 (directAnnotation). CD4+ T cells
motiftransfac_pro__M038443.720.0778ELK4 (directAnnotation). CD4+ T cells
motiftaipale_tf_pairs__ERF_HOXA3_RSCGGAWNNNNNNNYMATTA_CAP_repr3.650.0769ERF; HOXA3 (directAnnotation). CD4+ T cells
motiftaipale_tf_pairs__TEAD4_CEBPD_NTTRCGYAANNNNNNRGWATGY_CAP3.650.0768CEBPD; TEAD4 (directAnnotation). CD4+ T cells
motiftaipale_tf_pairs__ELF2_NATGCGGAAGTR_HT3.640.0767ELF2 (directAnnotation). CD4+ T cells
motifjaspar__MA1509.13.60.0762IRF6 (directAnnotation). CD4+ T cells
motifjaspar__MA1939.13.50.075SREBF2 (directAnnotation). CD4+ T cells
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Motifs and TFs regulating down-regulated DEGs in resistant group of the post-treatment samples
motifmotifNESAUCTF_highConfCell_type
motifjaspar__MA0604.18.190.12ATF1 (inferredBy_Orthology). CD4+ T cells
motiftaipale_cyt_meth__CREB1_NRTGACGTN_eDBD_repr6.460.103CREB1 (directAnnotation). CD4+ T cells
motiftransfac_pro__M018615.610.0939ATF1 (directAnnotation). CD4+ T cells
motifmetacluster_111.34.980.0874ATF1; ATF3; CREB1; CREB1; CREB1; CREB1; CREB1; CREM; CREM; CREM; CREM; E4F1; E4F1 (directAnnotation). CREB1; CREB1; CREM; JDP2 (inferredBy_Orthology). CD4+ T cells
motifdbtfbs__GMEB1_K562_ENCSR928KOR_merged_N14.860.0861GMEB1 (directAnnotation). CD4+ T cells
motiftransfac_pro__M008014.770.0852ATF1; ATF2; ATF3; ATF4; ATF7; CREB1; CREM (directAnnotation). ATF7-NPFF (inferredBy_Orthology). CD4+ T cells
motifdbtfbs__GMEB2_HepG2_ENCSR745VSQ_merged_N14.770.0852GMEB2 (directAnnotation). CD4+ T cells
motifmetacluster_111.44.730.0848ATF1; ATF1; ATF1; ATF1; ATF1; ATF1; ATF2; ATF2; ATF2; ATF2; ATF2; ATF2; ATF2; ATF2; ATF2; ATF2; ATF3; ATF3; ATF3; ATF3; ATF3; ATF4; ATF4; ATF5; ATF6; ATF6B; ATF7; ATF7; ATF7; BATF3; BATF3; CREB1; CREB1; CREB1; CREB1; CREB1; CREB1; CREB1; CREB1; CREB1; CREB1; CREB3; CREB3L4; CREB3L4; CREB5; CREB5; CREB5; CREM; CREM; CREM; CREM; CREM; FOSB; FOSL1; FOSL1; FOSL2; JDP2; JDP2; JDP2; JUN; JUNB; JUNB; JUNB; JUND; JUND; JUND; JUND; JUND; XBP1; XBP1; XBP1; ZNF629 (directAnnotation). ATF1; ATF1; ATF1; ATF2; ATF2; ATF3; ATF6; ATF6B; ATF7; ATF7; ATF7; ATF7-NPFF; ATF7-NPFF; ATF7-NPFF; ATF7-NPFF; BATF; BATF2; BATF3; CREB1; CREB1; CREB3; CREB3L1; CREB3L2; CREB3L3; CREB3L4; CREM; FOS; FOSB; FOSL1; FOSL2; JDP2; JDP2 (inferredBy_Orthology). CD4+ T cells
motifhocomoco__GMEB2_HUMAN.H11MO.0.D4.460.0821GMEB2 (directAnnotation). CD4+ T cells
motiftransfac_public__M000394.430.0817CREB1 (directAnnotation). CD4+ T cells
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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

ETS1

cisbp__M02645upCD4+ T cellspost

PRDM1

metacluster_187.2upCD4+ T cellspost

ATF3

metacluster_111.3downCD4+ T cellspost

CREM

metacluster_111.3downCD4+ T cellspost

ATF3

transfac_pro__M00801downCD4+ T cellspost

CREM

transfac_pro__M00801downCD4+ T cellspost

ATF3

metacluster_111.4downCD4+ T cellspost

CREM

metacluster_111.4downCD4+ T cellspost

FOSB

metacluster_111.4downCD4+ T cellspost

FOSL2

metacluster_111.4downCD4+ T cellspost
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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."