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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

TRPT1

ENSG000001497430.8931721.42e-183.98e-1410.985Malignant cellsNA

B9D1

ENSG000001086410.891764.33e-081.21e-030.90.701Malignant cellsNA

RNF214

ENSG000001672570.8917186.75e-071.89e-020.8270.709Malignant cellsNA

RBL2

ENSG000001034790.890962.69e-077.51e-030.9070.776Malignant cellsNA

CMC4

ENSG000001827120.8906187.71e-112.16e-060.940.754Malignant cellsNA

AC007246.3

NA0.8899125.25e-101.47e-050.940.791Malignant cellsNA

RILP

ENSG000002741450.8879229.00e-112.52e-060.9530.687Malignant cellsNA

LRRC37BP1

ENSG000002504620.8872565.21e-071.46e-020.980.97Malignant cellsNA

QKI

ENSG000001125310.8849281.12e-133.12e-0910.97Malignant cellsNA

STX3

ENSG000001669000.8848724.32e-071.21e-020.9070.739Malignant cellsNA

DYNLT1

ENSG000001464250.8843854.58e-231.28e-1810.985Malignant cellsNA

RAD17

ENSG000002766180.8834921.13e-073.17e-030.940.739Malignant cellsNA

DMTF1

ENSG000001351640.8825077.25e-102.03e-050.9870.948Malignant cellsNA

SNX10

ENSG000000863000.8817523.21e-118.98e-070.9730.769Malignant cellsNA

TCAIM

ENSG000001791520.881522.39e-106.68e-060.960.761Malignant cellsNA

ING4

ENSG000001116530.8803693.42e-089.56e-040.8670.701Malignant cellsNA

APLP2

ENSG000000842340.8799755.90e-231.65e-1811Malignant cellsNA

KIF2A

ENSG000000687960.879731.13e-113.16e-070.9870.948Malignant cellsNA

MLST8

ENSG000001679650.8776661.42e-093.96e-050.9870.888Malignant cellsNA

INO80C

ENSG000001533910.877116.31e-081.76e-030.980.94Malignant cellsNA

SMIM14

ENSG000001636830.8766112.66e-087.45e-0410.985Malignant cellsNA

S100A16

ENSG000001886430.8738064.92e-111.38e-0610.925Malignant cellsNA

IFNGR2

ENSG000002627950.8710422.17e-156.06e-1110.97Malignant cellsNA

TMSB4XP4

ENSG000002235510.8683641.11e-103.11e-060.90.694Malignant cellsNA

KIAA0430

NA0.8679533.92e-071.10e-020.8130.567Malignant cellsNA

ACAD8

ENSG000001514980.8653451.67e-064.68e-020.8270.582Malignant cellsNA

MGAT4B

ENSG000002845010.8650492.75e-097.68e-050.9730.955Malignant cellsNA

TMEM106B

ENSG000001064600.8625351.13e-093.15e-0511Malignant cellsNA

FIBP

ENSG000001725000.8614261.20e-213.35e-1710.993Malignant cellsNA

PPCS

ENSG000001271250.859242.20e-126.14e-080.9730.94Malignant cellsNA

C6orf203

NA0.8589477.35e-072.06e-020.760.634Malignant cellsNA

GCA

ENSG000001152710.8576861.47e-094.11e-050.960.657Malignant cellsNA

FAM89A

ENSG000001821180.8574531.36e-093.81e-050.780.418Malignant cellsNA

FAM126A

NA0.8541091.15e-073.21e-030.9870.97Malignant cellsNA

PRKCA

ENSG000001542290.8539119.93e-132.78e-080.9930.955Malignant cellsNA

MPG

ENSG000001031520.8537655.30e-081.48e-030.980.94Malignant cellsNA

SYNGR1

ENSG000001003210.8534216.80e-111.90e-060.980.963Malignant cellsNA

ARNTL2

NA0.8513624.78e-071.34e-0210.978Malignant cellsNA

MRGBP

ENSG000001011890.8505141.21e-193.38e-1510.993Malignant cellsNA

ZER1

ENSG000001604450.8498548.86e-072.48e-020.860.657Malignant cellsNA

OAF

ENSG000001842320.8496283.22e-098.99e-050.9530.836Malignant cellsNA

HSDL1

ENSG000001031600.8476217.06e-101.97e-050.9470.776Malignant cellsNA

CLU

ENSG000001208850.8471137.34e-072.05e-0211Malignant cellsNA

NBPF14

ENSG000002706290.8468163.68e-071.03e-0210.955Malignant cellsNA

FKBP1C

ENSG000001982250.8467931.24e-093.47e-050.7930.612Malignant cellsNA

UNC50

ENSG000001154460.8452093.39e-139.47e-0910.873Malignant cellsNA

POPDC3

ENSG000001324290.8451891.02e-102.86e-060.9870.806Malignant cellsNA

RNASEK

ENSG000002192000.8439811.95e-245.45e-2011Malignant cellsNA

HHLA3

ENSG000001975680.841825.55e-101.55e-050.940.97Malignant cellsNA

SLC25A4

ENSG000001517290.839932.49e-106.97e-060.9730.739Malignant 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."