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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: GSE140440

Dataset summary for GSE140440

Datast informationDatasetGSE140440
PMID32513898
Raw data ID/linkPRJNA589746
OrganismHomo sapiens
SourceDU145 and PC cell lines
TissueCell line
Cancer type level1Prostate cancer
Cancer type level2Prostate cancer
Regimendocetaxel
Drug typeChemotherapy
Sample sizeresistant 2, sensitive 2
Cell number284
Extract protocolSMART-seq v4
Data processingNA
Public datePublic on Sep 01, 2020
DescriptionThis dataset has 1 cell line with a sensitive pre-treatment sample and a resistant post-treatment sample.

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Drug summary for GSE140440

Drug nameDrugBank IDDrug typeTargets nameTargets uniprot ID
"Docetaxel"

DB01248

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

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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

ZNF114

ENSG00000178150-0.8568573.41e-089.53e-040.4130.679Malignant cellsNA

ZXDA

ENSG00000198205-0.8572478.26e-072.31e-020.4270.731Malignant cellsNA

CCND1

ENSG00000110092-0.8578486.53e-131.83e-080.9731Malignant cellsNA

PHLDA2

ENSG00000274538-0.8581024.83e-091.35e-0411Malignant cellsNA

VASN

ENSG00000274334-0.8583648.90e-112.49e-060.3730.746Malignant cellsNA

RP11-473O4.4

NA-0.8593371.83e-075.12e-030.320.627Malignant cellsNA

RP4-675C20.4

NA-0.862041.35e-073.78e-030.5530.754Malignant cellsNA

DUSP2

ENSG00000158050-0.8621322.63e-087.36e-040.380.709Malignant cellsNA

PSMD13

ENSG00000185627-0.8621481.03e-172.88e-1311Malignant cellsNA

HAUS8

ENSG00000131351-0.8626061.79e-075.00e-030.70.888Malignant cellsNA

TFAM

ENSG00000108064-0.8631255.59e-161.56e-110.981Malignant cellsNA

TUBBP1

ENSG00000127589-0.8631691.37e-143.83e-100.4470.813Malignant cellsNA

CDCA2

ENSG00000184661-0.8639631.00e-062.81e-020.5470.799Malignant cellsNA

WDR75

ENSG00000115368-0.8647667.90e-122.21e-070.9470.993Malignant cellsNA

RPSAP6

ENSG00000214629-0.8653876.05e-081.69e-030.3670.701Malignant cellsNA

PSMD12

ENSG00000197170-0.8656282.58e-257.21e-2111Malignant cellsNA

POLR2D

ENSG00000144231-0.8662935.17e-091.45e-040.9731Malignant cellsNA

FNBP4

ENSG00000285182-0.867573.65e-071.02e-020.9130.978Malignant cellsNA

TSPAN4

ENSG00000214063-0.8678161.52e-064.26e-020.840.97Malignant cellsNA

PLIN4

ENSG00000167676-0.8679867.60e-072.13e-020.3930.679Malignant cellsNA

MIS18BP1

ENSG00000129534-0.8680381.08e-063.03e-020.820.963Malignant cellsNA

FOXP1-AS1

ENSG00000244203-0.8696241.42e-063.97e-020.40.672Malignant cellsNA

PEBP1

ENSG00000089220-0.8698224.92e-231.38e-1811Malignant cellsNA

EIF4G2

ENSG00000110321-0.8709077.44e-162.08e-1111Malignant cellsNA

CDKN2C

ENSG00000123080-0.872552.73e-077.63e-030.7530.925Malignant cellsNA

TIPIN

ENSG00000075131-0.8729811.19e-083.33e-040.9070.963Malignant cellsNA

RIC3

ENSG00000166405-0.8732232.51e-077.01e-030.180.463Malignant cellsNA

SAFB2

ENSG00000130254-0.8734861.89e-075.28e-030.9471Malignant cellsNA

PITRM1

ENSG00000107959-0.8793154.20e-071.17e-020.8870.933Malignant cellsNA

DAPK1

ENSG00000196730-0.880374.82e-091.35e-040.3470.694Malignant cellsNA

BCL2L12

ENSG00000126453-0.8820871.88e-105.26e-060.920.97Malignant cellsNA

HJURP

ENSG00000123485-0.8822238.78e-082.45e-030.6530.828Malignant cellsNA

TCEB3

NA-0.8826118.88e-122.48e-070.9671Malignant cellsNA

NME1

ENSG00000239672-0.8830791.81e-265.05e-2211Malignant cellsNA

FCHO1

ENSG00000130475-0.8859039.55e-072.67e-020.6130.866Malignant cellsNA

PUS7

ENSG00000091127-0.8881042.42e-076.77e-030.8470.955Malignant cellsNA

RP11-20I23.8

NA-0.8897111.65e-064.60e-020.380.679Malignant cellsNA

AC098823.3

NA-0.8920213.71e-081.04e-030.6870.858Malignant cellsNA

ZNF593

ENSG00000142684-0.8930541.47e-084.12e-040.9871Malignant cellsNA

WDR46

ENSG00000226916-0.8957941.17e-073.27e-030.9130.963Malignant cellsNA

SMPD4

ENSG00000136699-0.8963157.88e-092.20e-040.9331Malignant cellsNA

ECT2

ENSG00000114346-0.89662.86e-078.00e-0311Malignant cellsNA

DDA1

ENSG00000130311-0.9005392.92e-098.16e-050.9930.993Malignant cellsNA

RP11-120D5.1

NA-0.9014487.67e-082.14e-030.3870.724Malignant cellsNA

POLR1E

ENSG00000137054-0.9067145.31e-071.48e-020.6470.881Malignant cellsNA

NOL11

ENSG00000130935-0.907318.07e-152.26e-1010.993Malignant cellsNA

ASF1B

ENSG00000288210-0.9082072.09e-095.85e-050.8330.955Malignant cellsNA

KCNG3

ENSG00000171126-0.9090735.48e-071.53e-020.3470.642Malignant cellsNA

ZNF296

ENSG00000170684-0.9092188.52e-112.38e-060.2870.694Malignant cellsNA

RP11-697E22.2

NA-0.9099631.98e-085.55e-040.440.754Malignant 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 Pathway9.80e-064.90e-05235278111623467Malignant cellsADAM9,ANXA2,AREG,BCAT1,BIRC5,BRCA1,CCND2,CDCP1,CDK6,CDKN1A,DNMT1,FAM168A,GSK3B,HOXA13,IGF2BP1,JUN,MAP1LC3B,PARP1,SOCS2,SPRY2,TGFB1,TGFBR2,PBK,TYMS,VEGFA,AAMDC,ADAM22,SLC25A5,AGR2,ANXA1,BCL10,BTG1,BUB1,CBL,CCNA2,CCNB1,CDK1,CCND1,CCNG2,CD44,HSPD1,CLTC,CLU,CUL4B,CYLD,DUSP2,DHFR,E2F2,ENG,ERCC1,ETS1,EZH2,FANCD2,FGFR1,FUS,FZD1,GPER1,GRB2,GCLM,SLC16A3,HMGB2,HMGN5,HSPA8,EIF4A3,IL1B,CXCL8,ING4,ITGA5,ITGB1,KIF11,KLF4,LDHA,MXD4,NF2,MYBL2,MYO10,NOTCH3,PARP8,PDCD4,PLK1,PSMB5,PTPN12,RAD51,RAB22A,RAB27A,RICTOR,RRM1,RRM2,ROCK2,SDC2,SMC4,SNAI2,SRI,STARD10,TERT,TFAM,TMEM54,TOP2B,USP14,USP22,PLAU,ERCC4,YEATS4,PFKFB3,GNAS,HMGCS1,INSIG1,ITGB3,PRKCA,RCN1,SQLE,SPHK1,GGPS1,SAFB2,PDSS1,ACAT2
Irregularity in Drug Uptake and Drug Efflux1.60e-013.60e-01235237623467Malignant cellsABCB1,ABCC2,ABCA10,ABCF2,ABCE1,ABCG1
Drug Inactivation by Structure Modification2.80e-013.60e-01235227423467Malignant cellsGSS,NME1,CMPK1,CYP51A1
Aberration of the Drug's Therapeutic Target2.90e-013.60e-012352901123467Malignant cellsBRCA1,CDK6,DHFR,EZH2,FGFR1,IL1B,JAK1,COMT,DPP4,MAOA,TOP2A
Epigenetic Alteration of DNA, RNA or Protein1.00e+001.00e+0023524552023467Malignant cellsDNMT1,GSK3B,H2AFY,HOXA13,EIF4G2,SPRY2,TYMS,EZH2,CXCL8,PDCD4,SMC4,TIMP1,SNHG1,LINC00261,GDI2,CDK14,CDR1,MX1,LINC00707,RP11-166P13.3


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
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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
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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

KLF13

metacluster_195.2upMalignant cellsNA

KLF9

metacluster_195.2upMalignant cellsNA

KLF4

metacluster_195.2upMalignant cellsNA

KLF7

metacluster_195.2upMalignant cellsNA

KLF13

hocomoco__KLF13_HUMAN.H11MO.0.DupMalignant cellsNA

KLF13

transfac_pro__M07461upMalignant cellsNA

KLF4

transfac_pro__M07461upMalignant cellsNA

KLF7

transfac_pro__M07461upMalignant cellsNA

KLF9

transfac_pro__M07461upMalignant cellsNA

KLF7

metacluster_170.2upMalignant 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."