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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

OSBPL8

ENSG000000910390.3617040.00e+000.00e+000.7450.59Malignant cellsNA

PTTG1IP

ENSG000001832550.3614110.00e+000.00e+000.6370.464Malignant cellsNA

GRB2

ENSG000001778850.3611570.00e+000.00e+000.7650.628Malignant cellsNA

TXNDC17

ENSG000001292350.3610660.00e+000.00e+000.940.886Malignant cellsNA

LSM6

ENSG000001641670.3600270.00e+000.00e+000.7750.651Malignant cellsNA

NIPBL

ENSG000001641900.3597290.00e+000.00e+000.6830.517Malignant cellsNA

NBPF1

ENSG000002194810.359590.00e+000.00e+000.6210.439Malignant cellsNA

TTC1

ENSG000001133120.3595640.00e+000.00e+000.5690.377Malignant cellsNA

PTPN1

ENSG000001963960.3588460.00e+000.00e+000.5160.306Malignant cellsNA

TOP1

ENSG000001989000.3586870.00e+000.00e+000.9290.879Malignant cellsNA

MARS

NA0.3576780.00e+000.00e+000.5370.343Malignant cellsNA

WDR60

NA0.3576420.00e+000.00e+000.5040.289Malignant cellsNA

FAM89B

ENSG000001769730.3575070.00e+000.00e+000.7290.569Malignant cellsNA

PPM1G

ENSG000001152410.3570780.00e+000.00e+000.980.965Malignant cellsNA

H2AFY

NA0.3568590.00e+000.00e+000.9880.983Malignant cellsNA

ALKBH2

ENSG000001890460.3563840.00e+000.00e+000.7970.674Malignant cellsNA

APOA1BP

NA0.3560590.00e+000.00e+000.8830.801Malignant cellsNA

SOX2

ENSG000001814490.3560310.00e+000.00e+000.2570.05Malignant cellsNA

PREX1

ENSG000001241260.3556430.00e+000.00e+000.2940.072Malignant cellsNA

CALR

ENSG000001792180.355350.00e+000.00e+000.9310.899Malignant cellsNA

RPS29

ENSG000002137410.3547570.00e+000.00e+0011Malignant cellsNA

CITED2

ENSG000001644420.3543680.00e+000.00e+000.3390.136Malignant cellsNA

PEX5L

ENSG000001147570.3542890.00e+000.00e+000.2830.066Malignant cellsNA

ASRGL1

ENSG000001621740.3542590.00e+000.00e+000.810.729Malignant cellsNA

DTX3

ENSG000001784980.3537920.00e+000.00e+000.5750.377Malignant cellsNA

IFT52

ENSG000001010520.3537850.00e+000.00e+000.6550.462Malignant cellsNA

MRPS18A

ENSG000000960800.3535340.00e+000.00e+000.6280.428Malignant cellsNA

B4GALT5

ENSG000001584700.3533540.00e+000.00e+000.4870.282Malignant cellsNA

WIPI2

ENSG000001579540.3531840.00e+000.00e+000.9010.809Malignant cellsNA

MRPL9

ENSG000001434360.3528720.00e+000.00e+000.9590.903Malignant cellsNA

USMG5

NA0.351860.00e+000.00e+000.9950.989Malignant cellsNA

KIN

ENSG000001516570.3517480.00e+000.00e+000.5060.301Malignant cellsNA

GALNT11

ENSG000001782340.3506930.00e+000.00e+000.6770.522Malignant cellsNA

RAD1

ENSG000001134560.3498210.00e+000.00e+000.6530.477Malignant cellsNA

FDPS

ENSG000001607520.3495240.00e+000.00e+000.9170.847Malignant cellsNA

CENPU

ENSG000001517250.3492230.00e+000.00e+000.7830.739Malignant cellsNA

PIN4

ENSG000001023090.3487210.00e+000.00e+000.8350.726Malignant cellsNA

SPATC1L

ENSG000002746790.3485950.00e+000.00e+000.5750.372Malignant cellsNA

IPO7

ENSG000002053390.3485010.00e+000.00e+000.630.46Malignant cellsNA

DYRK2

ENSG000001273340.3484090.00e+000.00e+000.5090.317Malignant cellsNA

HSPA5

ENSG000000445740.3473856.39e-401.20e-350.5640.466Malignant cellsNA

TSFM

ENSG000001232970.3473590.00e+000.00e+000.6670.497Malignant cellsNA

PAIP2

ENSG000001207270.3470670.00e+000.00e+000.830.708Malignant cellsNA

TIMM50

ENSG000001051970.3470230.00e+000.00e+000.7830.663Malignant cellsNA

PITHD1

ENSG000000577570.3469410.00e+000.00e+000.5560.365Malignant cellsNA

MED30

ENSG000001647580.3466380.00e+000.00e+000.4990.299Malignant cellsNA

MT-CO1

ENSG000001988040.3466030.00e+000.00e+0011Malignant cellsNA

PDZRN3

ENSG000001214400.3463040.00e+000.00e+000.3410.152Malignant cellsNA

ATP2A2

ENSG000001744370.3459310.00e+000.00e+000.6360.451Malignant cellsNA

TBCA

ENSG000001715300.3452110.00e+000.00e+000.9970.991Malignant 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."