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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 (This dataset does not contain this module)

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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: GSE115251

Dataset summary for GSE115251

Datast informationDatasetGSE115251
PMID31391581
Raw data ID/linkPRJNA474340
OrganismHomo sapiens
SourceKelly cell line
TissueCell line
Cancer type level1Neuroblastoma
Cancer type level2Neuroblastoma
RegimenTAE684
Drug typeTargeted therapy
Sample sizeresistant 1, sensitive 1
Cell number11790
Extract protocol10x genomics
Data processingCellRanger
Public datePublic on Aug 07, 2019
DescriptionThis dataset has 2 cell lines, each with a sensitive pre-treatment sample and a resistant post-treatment sample.

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Drug summary for GSE115251

Drug nameDrugBank IDDrug typeTargets nameTargets uniprot ID
"TAE684" 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
Umap of cell clustersboxplotCell ratio of drug-resistant and sensitive groups within each clusterboxplot

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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.)

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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

RBM39

ENSG000001310510.6638110.00e+000.00e+000.9870.938Malignant cellsNA

KLHDC8A

ENSG000001628730.660470.00e+000.00e+000.4580.065Malignant cellsNA

CLDN5

ENSG000001841130.6598330.00e+000.00e+000.2740.006Malignant cellsNA

MT-ND4L

ENSG000002129070.6557940.00e+000.00e+000.9630.861Malignant cellsNA

C12orf75

ENSG000002351620.6493330.00e+000.00e+000.8240.605Malignant cellsNA

RPL38

ENSG000001728090.6492420.00e+000.00e+0011Malignant cellsNA

TUBB4B

ENSG000001882290.6482610.00e+000.00e+000.9440.869Malignant cellsNA

ZNF385D

ENSG000001517890.6469980.00e+000.00e+000.4110.08Malignant cellsNA

TAGLN3

ENSG000001448340.6457770.00e+000.00e+000.4990.166Malignant cellsNA

RNF157

ENSG000001415760.6416080.00e+000.00e+000.5540.187Malignant cellsNA

ARPC3

ENSG000001112290.6414930.00e+000.00e+000.9940.957Malignant cellsNA

RPS21

ENSG000001718580.639850.00e+000.00e+0011Malignant cellsNA

MYL12A

ENSG000001016080.6356360.00e+000.00e+000.8130.562Malignant cellsNA

MT-ND4

ENSG000001988860.6341390.00e+000.00e+0011Malignant cellsNA

PTGES3

ENSG000001109580.6325250.00e+000.00e+000.9980.99Malignant cellsNA

PGF

ENSG000001196300.6306014.34e-448.08e-400.4870.428Malignant cellsNA

CD81

ENSG000001106510.6268220.00e+000.00e+000.6230.269Malignant cellsNA

CDK6

ENSG000001058100.6253970.00e+000.00e+000.9030.77Malignant cellsNA

VAPA

ENSG000001015580.6243870.00e+000.00e+000.9590.863Malignant cellsNA

SRSF9

ENSG000001117860.6241520.00e+000.00e+0010.999Malignant cellsNA

EDF1

ENSG000001072230.6238320.00e+000.00e+0011Malignant cellsNA

POPDC3

ENSG000001324290.6228330.00e+000.00e+000.6090.289Malignant cellsNA

PLEKHA5

ENSG000000521260.6220190.00e+000.00e+000.7060.482Malignant cellsNA

RAN

ENSG000001323410.6219360.00e+000.00e+0011Malignant cellsNA

EIF6

ENSG000002423720.6210150.00e+000.00e+000.8710.657Malignant cellsNA

RPRM

ENSG000001775190.6180250.00e+000.00e+000.340Malignant cellsNA

DYNLRB1

ENSG000001259710.6122390.00e+000.00e+000.9460.814Malignant cellsNA

SURF4

ENSG000002809510.6114510.00e+000.00e+000.8060.579Malignant cellsNA

GNAS

ENSG000000874600.6023540.00e+000.00e+0011Malignant cellsNA

ASS1

ENSG000001307070.6012060.00e+000.00e+000.5830.335Malignant cellsNA

DPH7

ENSG000001483990.5994510.00e+000.00e+000.7740.517Malignant cellsNA

PRRC2B

ENSG000002887010.5961940.00e+000.00e+000.8060.57Malignant cellsNA

BEX2

ENSG000001331340.5961710.00e+000.00e+000.8280.599Malignant cellsNA

POLR2L

ENSG000001777000.5956880.00e+000.00e+000.9790.91Malignant cellsNA

ZFP36L1

ENSG000001856500.5937820.00e+000.00e+000.360.012Malignant cellsNA

SLC25A48

ENSG000001458320.5924260.00e+000.00e+000.3150Malignant cellsNA

NDUFV2

ENSG000001781270.5922010.00e+000.00e+000.9960.979Malignant cellsNA

TPX2

ENSG000000883250.5892540.00e+000.00e+000.7420.692Malignant cellsNA

C1orf54

ENSG000001182920.5882980.00e+000.00e+000.4230.057Malignant cellsNA

CHMP1B

ENSG000002551120.5858960.00e+000.00e+000.5830.249Malignant cellsNA

CDC42EP4

ENSG000001796040.5858650.00e+000.00e+000.5610.224Malignant cellsNA

GKAP1

ENSG000001651130.5843660.00e+000.00e+000.3110.084Malignant cellsNA

COL2A1

ENSG000001392190.5792990.00e+000.00e+000.3470.024Malignant cellsNA

WBP5

NA0.5762460.00e+000.00e+000.7510.472Malignant cellsNA

PRKAR1A

ENSG000001089460.5754980.00e+000.00e+000.6980.412Malignant cellsNA

DDX27

ENSG000001242280.5746770.00e+000.00e+000.7580.512Malignant cellsNA

ATXN7L3B

ENSG000002537190.5721690.00e+000.00e+000.7150.416Malignant cellsNA

AURKA

ENSG000000875860.5714421.22e-122.29e-080.4890.456Malignant cellsNA

MED10

ENSG000001333980.5713970.00e+000.00e+000.8790.709Malignant cellsNA

TAF7

ENSG000001789130.5683530.00e+000.00e+000.8910.727Malignant 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 Pathway7.80e-133.90e-1213987819923467Malignant cellsAKAP1,ANXA2,AURKA,BCL11A,BCAT1,CTSL,CDK4,CDK6,CDKN1A,CIAPIN1,CTNNB1,DLK1,EPAS1,GSTP1,SLC2A1,HIF1A,HMGA1,ID1,MAGEA6,MAGEA12,NFE2L2,PARP1,PTEN,PTPN11,KRAS,RALBP1,RHOA,RPS6,SFRP1,SHC1,SOX2,SOX9,STMN1,TYMS,AKAP12,ANK2,BAG1,BID,HSPA5,BRD7,BTG1,CCNB1,CCND1,ALCAM,DKK1,DHFR,HSP90B1,EZH2,FANCA,FYN,GAPDH,GRB2,HDAC1,HMGN5,HNRNPU,HSPB1,IDH1,EIF4A1,ITGB1,KDM5B,LDHA,MAP3K1,MYCN,NFATC3,OAZ2,PDE4D,PSMG2,PTPN1,RAC1,RAP1B,HRAS,RAB22A,RRM1,HNRNPA1,RSU1,SDC2,SLAIN1,SMARCC1,SOD2,SRI,STK4,TMEM54,TOP1,YY1,UBE2C,USP14,YBX1,YEATS4,FASN,GNAS,CALR,RET,NPM1,CEBPD,MDK,PRKCA,TM7SF2,PMVK,QPRT
Aberration of the Drug's Therapeutic Target8.70e-022.20e-01139890923467Malignant cellsCDK4,CDK6,DHFR,EZH2,IDH1,SF3B1,RET,NPM1,COMT
Drug Inactivation by Structure Modification2.20e-013.60e-01139827323467Malignant cellsGSTP1,GSS,SOD2
Irregularity in Drug Uptake and Drug Efflux9.00e-011.00e+00139837123467Malignant cellsSLC2A1
Epigenetic Alteration of DNA, RNA or Protein1.00e+001.00e+001398455923467Malignant cellsH2AFY,EIF4G2,TYMS,EZH2,GAPDH,IDH1,MALAT1,RET,SMYD2


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
motiftaipale_cyt_meth__E2F2_GCGCGCGCGYW_eDBD_repr3.840.0626E2F2 (directAnnotation). Malignant cells
motiftaipale_tf_pairs__ETS2_RCCGGAAGTG_HT3.750.0618ETS2 (directAnnotation). Malignant cells
motiftaipale_tf_pairs__E2F1_HES7_RRCRCGYGYNNNNSGCGCSN_CAP_repr3.690.0613E2F1; HES7 (directAnnotation). Malignant cells
motifkznf__ZNF25_Imbeault2017_OM_MEME3.690.0613ZNF25 (directAnnotation). Malignant cells
motiftaipale_tf_pairs__ETV5_HES7_NNCACGTGNNNNCCGGAANN_CAP3.360.0586ETV5; HES7 (directAnnotation). Malignant cells
motifmetacluster_191.33.210.0573EHF; ELF1; ELF1; ELF1; ELF4; ELK1; ELK3; ELK3; ELK4; ELK4; ERF; ETS1; ETS2; ETV3; ETV4; ETV5; FEV; FEV; FLI1; FLI1; GABPA; GABPA; GABPA; GABPA; GABPA; GABPA; SPDEF; ZNF200 (directAnnotation). ELK1; ELK1; ELK3; ELK3; ELK4; ELK4; ETV1; ETV1; ETV4; ETV4; ETV4; ETV5; GABPA; GABPA (inferredBy_Orthology). Malignant cells
motiftaipale_tf_pairs__HOXB2_ETV4_ACCGGAAATGAN_CAP3.180.0571ETV4; HOXB2 (directAnnotation). Malignant cells
motifkznf__ZFP57_Imbeault2017_RP_ChIP-seq3.170.057ZFP57 (directAnnotation). Malignant cells
motiftaipale_tf_pairs__ELF2_NATGCGGAAGTR_HT3.150.0569ELF2 (directAnnotation). Malignant cells
motifkznf__ZNF777_Imbeault2017_RP_ChIP-seq3.110.0565ZNF777 (directAnnotation). Malignant cells
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Motifs and TFs regulating down-regulated DEGs in resistant group
motifmotifNESAUCTF_highConfCell_type
motifhdpi__NFIX3.880.0567NFIX (directAnnotation). Malignant cells
motiftransfac_pro__M038133.650.0553POU3F3 (directAnnotation). Malignant cells
motifhocomoco__MNX1_HUMAN.H11MO.0.D3.510.0543MNX1 (directAnnotation). Malignant cells
motifhdpi__ZNF1933.480.0541ZSCAN9 (directAnnotation). Malignant cells
motifhdpi__FOXM13.350.0533FOXM1 (directAnnotation). Malignant cells
motiftransfac_pro__M060743.260.0527ZNF732 (directAnnotation). Malignant cells
motifjaspar__MA1106.13.250.0527HIF1A (directAnnotation). Malignant cells
motifhocomoco__OTX1_HUMAN.H11MO.0.D3.250.0526OTX1 (directAnnotation). Malignant cells
motifhocomoco__TYY2_HUMAN.H11MO.0.D3.160.0521YY2 (directAnnotation). Malignant cells
motiftransfac_pro__M057683.110.0518ZNF544 (directAnnotation). Malignant 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

HIF1A

jaspar__MA1106.1downMalignant cellsNA

ETV5

taipale_tf_pairs__ETV5_HES7_NNCACGTGNNNNCCGGAANN_CAPdownMalignant cellsNA

ETV5

metacluster_191.3downMalignant cellsNA

FEV

metacluster_191.3downMalignant 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."