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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

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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: GSE207422_Sin

Dataset summary for GSE207422_Sin

Datast informationDatasetGSE207422_Sin
PMID36869384
Raw data ID/linkhttps://ngdc.cncb.ac.cn/gsa-human/browse/HRA001033
OrganismHomo sapiens
Sourcepatients
TissueTumor tissue
Cancer type level1Lung cancer
Cancer type level2EGFR/ALK mutation negative non-small cell lung cancer (NSCLC)
Regimensintilimab + carboplatin + (docetaxel or pemetrexed or emcitabine)
Drug typeImmunotherapy
Sample sizepost (resistant 5, sensitive 2)
Cell number22187
Extract protocolBD Rhapsody system
Data processing BD Rhapsody Whole Transcriptome Analysis (WTA) Pipeline
Public datePublic on Mar 21, 2023
DescriptionThis dataset has 7 patients with post-treatment samples.

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Drug summary for GSE207422_Sin

Drug nameDrugBank IDDrug typeTargets nameTargets uniprot ID
"Sintilimab"

DB15765

biotechPDCD1Q15116
"carboplatin" is not included in the drug list.
"Docetaxel"

DB01248

small moleculeTUBB1; MAP2; MAP4; MAPT; BCL2; NR1I2Q9H4B7; P11137; P27816; P10636; P10415; O75469
"Pemetrexed"

DB00642

small moleculeTYMS; ATIC; DHFR; GARTP04818; P31939; P00374; P22102
"emcitabine" 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.)

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

OAS3

ENSG000001113310.3265961.66e-193.99e-150.2680.079CD8+ T cellspost

BST2

ENSG000001303030.3233491.46e-193.51e-150.3220.115CD8+ T cellspost

CLDND1

ENSG000000808220.3215025.15e-081.24e-030.4450.313CD8+ T cellspost

BTG1

ENSG000001336390.3206733.07e-117.37e-070.8190.634CD8+ T cellspost

H2AFV

NA0.3195559.76e-122.35e-070.4170.255CD8+ T cellspost

MYADM

ENSG000001798200.3152821.94e-104.66e-060.3670.219CD8+ T cellspost

ISG20

ENSG000001721830.3148098.76e-192.10e-140.3160.117CD8+ T cellspost

BIRC3

ENSG000000234450.313851.04e-102.49e-060.4070.249CD8+ T cellspost

PDE3B

ENSG000001522700.3099832.62e-196.30e-150.2870.089CD8+ T cellspost

SURF4

ENSG000002809510.3073379.82e-182.36e-130.430.219CD8+ T cellspost

B2M

ENSG000002736860.3066560.00e+000.00e+0011CD8+ T cellspost

SH3BGRL3

ENSG000001426690.3056815.78e-161.39e-110.9570.923CD8+ T cellspost

GBP5

ENSG000001544510.3054982.81e-126.74e-080.60.409CD8+ T cellspost

HCP5

ENSG000002371050.3051571.09e-152.63e-110.4930.287CD8+ T cellspost

TMSB10

ENSG000000345100.3036962.69e-146.47e-100.8550.717CD8+ T cellspost

ATP5MC3

ENSG000001545180.3022116.70e-191.61e-140.4880.255CD8+ T cellspost

RAB3GAP1

ENSG000001158390.301981.67e-194.00e-150.2520.064CD8+ T cellspost

NASP

ENSG000001327800.3016851.35e-173.24e-130.3380.138CD8+ T cellspost

LGALS1

ENSG000001000970.299442.74e-116.59e-070.2940.143CD8+ T cellspost

PPDPF

ENSG000001255340.2984937.63e-161.83e-110.7180.511CD8+ T cellspost

GBP1

ENSG000001172280.2984097.72e-151.85e-100.4190.223CD8+ T cellspost

HIF1A

ENSG000001006440.2971162.54e-156.10e-110.3830.187CD8+ T cellspost

SNRPG

ENSG000001439770.296521.92e-174.60e-130.3680.168CD8+ T cellspost

CALR

ENSG000001792180.2947536.63e-111.59e-060.6910.523CD8+ T cellspost

NDUFS5

ENSG000001686530.2942542.93e-187.03e-140.450.223CD8+ T cellspost

ITGA1

ENSG000002139490.2921244.06e-149.75e-100.3740.191CD8+ T cellspost

IFI16

ENSG000001635650.2918638.42e-142.02e-090.7220.526CD8+ T cellspost

CYCS

ENSG000001721150.289032.46e-145.90e-100.3810.196CD8+ T cellspost

RHBDD2

ENSG000000054860.2889999.21e-152.21e-100.2880.121CD8+ T cellspost

ANP32B

ENSG000001369380.2859052.30e-095.53e-050.6740.543CD8+ T cellspost

ATP1B3

ENSG000000698490.2840423.67e-158.82e-110.3970.202CD8+ T cellspost

SQSTM1

ENSG000002840990.283346.37e-111.53e-060.3590.206CD8+ T cellspost

PARK7

ENSG000001162880.2833331.10e-132.63e-090.4480.266CD8+ T cellspost

ATP5MF

ENSG000002414680.2825491.62e-163.90e-120.4830.262CD8+ T cellspost

LMNB1

ENSG000001133680.2824464.58e-171.10e-120.2590.083CD8+ T cellspost

OAS2

ENSG000001113350.2816938.61e-162.07e-110.3110.128CD8+ T cellspost

PSMB3

ENSG000002759030.2809577.97e-191.91e-140.320.115CD8+ T cellspost

PPA1

ENSG000001808170.2805686.50e-151.56e-100.2780.111CD8+ T cellspost

PSMB2

ENSG000001260670.2790154.89e-171.18e-120.3950.187CD8+ T cellspost

SUMO2

ENSG000001886120.2789522.75e-166.61e-120.6690.426CD8+ T cellspost

CTSD

ENSG000001179840.2785944.07e-159.78e-110.3780.181CD8+ T cellspost

CD38

ENSG000000044680.2785181.52e-173.64e-130.2510.072CD8+ T cellspost

CFL1

ENSG000001727570.2783473.68e-168.84e-120.9870.983CD8+ T cellspost

PDIA6

ENSG000001438700.2763072.73e-156.55e-110.4330.226CD8+ T cellspost

ZFAND5

ENSG000001073720.2754341.45e-143.49e-100.30.13CD8+ T cellspost

TRA2B

ENSG000001365270.2752381.12e-142.68e-100.4570.257CD8+ T cellspost

SMAP2

ENSG000000840700.2741482.55e-086.13e-040.4570.317CD8+ T cellspost

RALA

ENSG000000064510.2734431.66e-163.99e-120.2530.081CD8+ T cellspost

IER5

ENSG000001627830.2719873.89e-129.35e-080.2920.138CD8+ T cellspost

UBALD2

ENSG000001852620.2714541.02e-142.44e-100.310.138CD8+ 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 5 known drug resistance mechanisms in malignant cells
boxplot
MechnismPvalFDRSignatureGenesetOverlapBackgroundCell typeEnriched Genes
Unusual Activation of Pro-survival Pathway1.10e-035.30e-031997811623467Malignant cellsCDKN1A,GSTP1,SLC2A1,HSPA1A,ID1,YWHAZ,FOXA1,GAPDH,LDHA,LRIG1,NOTCH3,NQO1,RAC1,UCP2,ENO1,ALDH1A1
Drug Inactivation by Structure Modification2.10e-014.50e-0119927123467Malignant cellsGSTP1
Irregularity in Drug Uptake and Drug Efflux2.70e-014.50e-0119937123467Malignant cellsSLC2A1
Epigenetic Alteration of DNA, RNA or Protein9.80e-011.00e+00199455123467Malignant cellsGAPDH
Aberration of the Drug's Therapeutic Target1.00e+001.00e+0019990023467Malignant cells

Enrichment results for 1 known drug resistance mechanisms in TME cells

boxplot
MechnismPvalFDRSignatureGenesetOverlapBackgroundCell typeEnriched Genes
Regulation by the Disease Microenvironment3.90e-013.90e-01168186223467B cellsTP53INP1,CXCR4
Regulation by the Disease Microenvironment2.00e-012.00e-01194186323467CD4+ T cellsCXCR4,FYN,SOCS3
Regulation by the Disease Microenvironment3.00e-013.00e-01349186423467CD8+ T cellsCXCR4,RHOB,SOCS3,MALAT1
Regulation by the Disease Microenvironment1.00e+001.00e+007186023467FibroblastsNA
Regulation by the Disease Microenvironment1.00e+001.00e+0041186023467Mast cellsNA
Regulation by the Disease Microenvironment3.00e-013.00e-01456186523467Mono_MacroVEGFA,CXCR4,SOCS3,VIM,FBP1
Regulation by the Disease Microenvironment3.50e-013.50e-01266186323467NeutrophilsPAK1,CXCR4,RHOB
Regulation by the Disease Microenvironment1.90e-021.90e-0227186223467NK cellsCX3CR1,CXCR4
Regulation by the Disease Microenvironment9.20e-029.20e-0264186223467pDCsCX3CR1,CXCR4
Regulation by the Disease Microenvironment1.00e+001.00e+0058186023467Plasma cellsNA

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
There is no signaficant down-regulated pathways in resistant groupboxplotboxplot

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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
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 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
motifhocomoco__TYY2_HUMAN.H11MO.0.D4.860.0798YY2 (directAnnotation). B cells
motiftransfac_pro__M020804.550.0762ISL2 (directAnnotation). B cells
motifmetacluster_141.24.330.0737E2F2; E2F3 (directAnnotation). B cells
motiftransfac_pro__M065004.190.0722ZNF614 (directAnnotation). B cells
motiftaipale_tf_pairs__ETV2_HES7_RSCGGAANNNNNNNCACGTGNN_CAP_repr4.180.072ETV2; HES7 (directAnnotation). B cells
motiftransfac_pro__M063014.060.0706ZNF404 (directAnnotation). B cells
motiftaipale__YY2_DBD_NNCCGCCATNW_repr3.850.0683YY2 (directAnnotation). B cells
motiftaipale_tf_pairs__ELK1_TEF_NSCGGAWNTTACGTAAN_CAP3.730.0669ELK1; TEF (directAnnotation). B cells
motiftfdimers__MD000323.660.0661GFI1; GFI1B; NKX3-2 (directAnnotation). B cells
motiftaipale_cyt_meth__JUND_NRTGACGCATN_eDBD_repr3.640.0658JUND (directAnnotation). B cells
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Motifs and TFs regulating down-regulated DEGs in resistant group of the post-treatment samples
motifmotifNESAUCTF_highConfCell_type
motiftransfac_pro__M057315.270.232ZNF660 (directAnnotation). B cells
motiftransfac_pro__M060374.570.206ZNF197 (directAnnotation). B cells
motifmetacluster_103.24.480.203ZNF136; ZNF680 (directAnnotation). B cells
motiftransfac_pro__M055424.290.196SNAPC4 (directAnnotation). B cells
motiftransfac_pro__M065394.180.192ZNF483 (directAnnotation). B cells
motifmetacluster_52.133.940.183LEF1; LEF1; LEF1; LEF1; TCF7; TCF7; TCF7L1; TCF7L1 (directAnnotation). B cells
motiftfdimers__MD003753.820.179KLF4; PITX3 (directAnnotation). B cells
motiftransfac_pro__M066613.820.179ZNF426 (directAnnotation). B cells
motiftransfac_pro__M058213.490.167ZNF880 (directAnnotation). B cells
motiftaipale__ZNF524_full_ACCCTTGAACCC_repr3.470.166ZNF524 (directAnnotation). B 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

KLF2

metacluster_163.1upB cellspost

KLF2

metacluster_170.2upB cellspost

CREM

transfac_pro__M00801upCD4+ T cellspost

IKZF2

tfdimers__MD00029upCD4+ T cellspost

TCF7

metacluster_52.13downCD4+ T cellspost

JUND

taipale_cyt_meth__JUND_NRTGACGCATN_eDBD_reprupCD8+ T cellspost

PRDM1

metacluster_2.9upCD8+ T cellspost

FOXP1

hocomoco__FOXP1_HUMAN.H11MO.0.AdownMast cellspost

CEBPD

taipale_tf_pairs__ETV2_CEBPD_RSCGGANNTTGCGYAAN_CAP_reprupMono/Macropost

FOSL2

metacluster_157.2upMono/Macropost
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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."