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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

CCS

ENSG000001739920.268250.00e+000.00e+000.3580.188Malignant cellsNA

C19orf10

NA0.2681410.00e+000.00e+000.9180.872Malignant cellsNA

TSPAN6

ENSG000000000030.2675890.00e+000.00e+000.4160.244Malignant cellsNA

RAB21

ENSG000000803710.2675380.00e+000.00e+000.5270.365Malignant cellsNA

LSM5

ENSG000001063550.2673120.00e+000.00e+000.9990.998Malignant cellsNA

FADS1

ENSG000001494850.2672220.00e+000.00e+000.7960.71Malignant cellsNA

RNF5

ENSG000002237670.26710.00e+000.00e+000.8580.782Malignant cellsNA

CD2BP2

ENSG000001692170.2670820.00e+000.00e+000.5090.345Malignant cellsNA

RAC1

ENSG000001362380.2667780.00e+000.00e+0011Malignant cellsNA

GLTP

ENSG000001394330.2667070.00e+000.00e+000.4350.264Malignant cellsNA

CEP290

ENSG000001987070.2662370.00e+000.00e+000.6050.474Malignant cellsNA

THAP9-AS1

ENSG000002510220.265960.00e+000.00e+000.5890.445Malignant cellsNA

NOSIP

ENSG000001425460.2655620.00e+000.00e+000.8630.781Malignant cellsNA

RIC3

ENSG000001664050.2653020.00e+000.00e+000.3620.203Malignant cellsNA

HDAC1

ENSG000001164780.264950.00e+000.00e+000.5640.42Malignant cellsNA

ADRM1

ENSG000001307060.2648980.00e+000.00e+000.9550.92Malignant cellsNA

NDUFS8

ENSG000001107170.2646180.00e+000.00e+000.990.977Malignant cellsNA

NEK2

ENSG000001176500.264443.34e-316.27e-270.3710.283Malignant cellsNA

ZNF787

ENSG000001424090.2642650.00e+000.00e+000.550.4Malignant cellsNA

DAP

ENSG000001129770.2641450.00e+000.00e+000.4080.234Malignant cellsNA

SNRNP40

ENSG000000606880.2638290.00e+000.00e+000.680.558Malignant cellsNA

ZDHHC24

ENSG000001741650.2636790.00e+000.00e+000.3580.201Malignant cellsNA

CD63

ENSG000001354040.2633540.00e+000.00e+000.970.942Malignant cellsNA

DDX39A

ENSG000001231360.2632660.00e+004.50e-430.6360.543Malignant cellsNA

HNRNPM

ENSG000000997830.2629620.00e+000.00e+000.960.937Malignant cellsNA

ENSA

ENSG000001434200.2629610.00e+000.00e+000.9930.986Malignant cellsNA

STX5

ENSG000001622360.2627930.00e+000.00e+000.3450.168Malignant cellsNA

NENF

ENSG000001176910.2625920.00e+000.00e+000.9920.984Malignant cellsNA

MAPRE1

ENSG000001013670.2624920.00e+000.00e+000.770.682Malignant cellsNA

SEPHS2

ENSG000001799180.2620960.00e+000.00e+000.5670.422Malignant cellsNA

RPL6

ENSG000000890090.2619390.00e+000.00e+0011Malignant cellsNA

MSRB1

ENSG000001987360.2613410.00e+000.00e+000.5050.346Malignant cellsNA

EIF4G2

ENSG000001103210.2613120.00e+000.00e+000.9520.924Malignant cellsNA

BRI3

ENSG000001647130.2613120.00e+000.00e+000.9570.925Malignant cellsNA

TWSG1

ENSG000001287910.2613010.00e+000.00e+000.2930.119Malignant cellsNA

EMC4

ENSG000001284630.2611550.00e+000.00e+000.9710.94Malignant cellsNA

PTPN2

ENSG000001753540.2611310.00e+000.00e+000.4550.29Malignant cellsNA

DEAF1

ENSG000002827120.2609080.00e+000.00e+000.3040.128Malignant cellsNA

C21orf59

NA0.2608720.00e+001.54e-440.5450.434Malignant cellsNA

PIGT

ENSG000001241550.2606550.00e+000.00e+000.5550.399Malignant cellsNA

TFG

ENSG000001143540.2604570.00e+000.00e+000.7660.666Malignant cellsNA

DDIT4

ENSG000001682090.2604370.00e+000.00e+000.3750.246Malignant cellsNA

ZNHIT3

ENSG000002785740.2603930.00e+000.00e+000.7940.692Malignant cellsNA

ILKAP

ENSG000001323230.2601090.00e+000.00e+000.4730.33Malignant cellsNA

ADCK1

ENSG000000637610.2598830.00e+000.00e+000.280.127Malignant cellsNA

SLC25A36

ENSG000001141200.2598690.00e+000.00e+000.7490.635Malignant cellsNA

TCTN1

ENSG000002048520.2594110.00e+000.00e+000.3160.148Malignant cellsNA

FBXW5

ENSG000001590690.2590650.00e+000.00e+000.6340.498Malignant cellsNA

SRP19

ENSG000001530370.2583520.00e+000.00e+000.7330.625Malignant cellsNA

ADNP

ENSG000001011260.258310.00e+000.00e+000.6060.465Malignant 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."