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	Dataset summary
	Drug summary
	Umap of single cell types and conditions (resistant and sensitive)
	Comparison of cell composition between the resistant and sensitive groups (This dataset does not contain this module)
	Comparison of intra-tumor heterogeneity (ITH) and epithelial-mesenchymal transition (EMT) scores of malignant cells between the resistant and sensitive groups
	Difference of cell-cell interactions between the resistant and sensitive groups (This dataset does not contain this module)
	Differentially expressed genes (DEGs) between the resistant and sensitive groups for each cell type
	Mechanism analysis of drug resistance-related DEGs for each cell type in the pre-treatment samples (This dataset does not contain this module)
	Mechanism analysis of drug resistance-related DEGs for each cell type in the post-treatment samples (This dataset does not contain this module)
	Mechanism analysis of drug resistance-related DEGs for each cell type in one patient or cell lines
	MicroRNAs (miRNAs) regulating drug resistance-related DEGs for Malignant cells
	Motifs and transcription factors (TFs) regulating drug resistance-related DEGs for each cell type
•	Differentially expressed genes act as transcription factors

Dataset: GSE140440

Dataset summary for GSE140440

Datast information	Dataset	GSE140440
	PMID	32513898
	Raw data ID/link	PRJNA589746
	Organism	Homo sapiens
	Source	DU145 and PC cell lines
	Tissue	Cell line
	Cancer type level1	Prostate cancer
	Cancer type level2	Prostate cancer
	Regimen	docetaxel
	Drug type	Chemotherapy
	Sample size	resistant 2, sensitive 2
	Cell number	284
	Extract protocol	SMART-seq v4
	Data processing	NA
	Public date	Public on Sep 01, 2020
	Description	This 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 name	DrugBank ID	Drug type	Targets name	Targets uniprot ID
"Docetaxel"	DB01248	small molecule	TUBB1; MAP2; MAP4; MAPT; BCL2; NR1I2	Q9H4B7; P11137; P27816; P10636; P10415; O75469

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Umap of single cell types and conditions (resistant and sensitive)

Umap 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 types	Umap of conditions
Umap of cell clusters	Cell ratio of drug-resistant and sensitive groups within each cluster

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Comparison of cell composition between the resistant and sensitive groups

In 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.)

In 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

Comparison 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 scores

Comparison of EMT scores

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Difference of cell-cell interactions between the resistant and sensitive groups

In 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.)

In 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.)

This 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

In 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.

In 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.

This 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 symbol	Gene id	avg_log2FC	p_val	p_val_adj	pct.1	pct.2	Cell type	Timepoint
RP11-452F19.3	NA	0.947353	5.98e-12	1.67e-07	0.967	0.881	Malignant cells	NA
RAB34	ENSG00000109113	0.944019	3.23e-11	9.04e-07	1	0.925	Malignant cells	NA
HLA-L	ENSG00000239618	0.943501	2.87e-11	8.02e-07	0.953	0.701	Malignant cells	NA
RCAN1	ENSG00000159200	0.942926	2.55e-11	7.12e-07	0.967	0.843	Malignant cells	NA
LPIN1	ENSG00000134324	0.940255	6.90e-10	1.93e-05	0.973	0.821	Malignant cells	NA
LAMC2	ENSG00000058085	0.939252	2.27e-07	6.35e-03	0.827	0.582	Malignant cells	NA
TMEM53	ENSG00000126106	0.939219	1.82e-07	5.10e-03	0.927	0.858	Malignant cells	NA
SMDT1	ENSG00000274112	0.936999	1.04e-16	2.90e-12	1	0.903	Malignant cells	NA
TST	ENSG00000128311	0.934304	4.49e-07	1.26e-02	0.827	0.604	Malignant cells	NA
PDE6D	ENSG00000156973	0.934129	8.92e-16	2.50e-11	0.993	0.896	Malignant cells	NA
C11orf68	ENSG00000175573	0.933479	4.24e-10	1.19e-05	0.98	0.94	Malignant cells	NA
LITAF	ENSG00000189067	0.933199	1.06e-08	2.96e-04	0.947	0.739	Malignant cells	NA
B3GNT5	ENSG00000176597	0.932775	1.63e-06	4.55e-02	0.96	0.813	Malignant cells	NA
TANK	ENSG00000136560	0.932443	2.13e-11	5.96e-07	0.993	0.851	Malignant cells	NA
ENPP4	ENSG00000001561	0.928359	1.45e-06	4.06e-02	0.9	0.739	Malignant cells	NA
GSTA4	ENSG00000170899	0.92809	2.59e-09	7.25e-05	0.92	0.724	Malignant cells	NA
CORO1B	ENSG00000172725	0.927635	1.39e-07	3.88e-03	0.967	0.888	Malignant cells	NA
ATRAID	ENSG00000138085	0.926845	5.12e-24	1.43e-19	1	0.993	Malignant cells	NA
MTHFSD	ENSG00000103248	0.926163	6.71e-07	1.88e-02	0.733	0.485	Malignant cells	NA
MXRA7	ENSG00000182534	0.923868	2.24e-19	6.25e-15	1	1	Malignant cells	NA
TIAM1	ENSG00000156299	0.923317	7.71e-08	2.15e-03	0.693	0.373	Malignant cells	NA
SDF2	ENSG00000132581	0.92298	1.07e-13	3.00e-09	0.98	0.836	Malignant cells	NA
SURF1	ENSG00000280627	0.922513	9.29e-10	2.60e-05	0.987	0.918	Malignant cells	NA
CD44	ENSG00000026508	0.921277	8.82e-12	2.47e-07	1	0.91	Malignant cells	NA
RNFT1	ENSG00000189050	0.920661	6.59e-09	1.84e-04	0.927	0.821	Malignant cells	NA
HLA-C	ENSG00000206435	0.918501	9.46e-15	2.64e-10	1	0.963	Malignant cells	NA
SOCS2-AS1	ENSG00000246985	0.917624	1.41e-08	3.95e-04	0.84	0.739	Malignant cells	NA
MIB1	ENSG00000101752	0.917494	7.70e-12	2.15e-07	1	0.925	Malignant cells	NA
PPIC	ENSG00000168938	0.916291	1.39e-12	3.88e-08	1	0.918	Malignant cells	NA
GOSR1	ENSG00000108587	0.914486	2.71e-12	7.58e-08	0.993	0.918	Malignant cells	NA
DDIT4	ENSG00000168209	0.914121	6.78e-15	1.90e-10	0.793	0.425	Malignant cells	NA
PPM1A	ENSG00000100614	0.912636	5.18e-09	1.45e-04	0.993	0.896	Malignant cells	NA
NPC1	ENSG00000141458	0.912157	2.64e-07	7.38e-03	0.94	0.799	Malignant cells	NA
PLPP1	ENSG00000067113	0.909909	3.58e-07	1.00e-02	0.8	0.634	Malignant cells	NA
BORCS7	ENSG00000166275	0.909856	2.19e-12	6.14e-08	1	0.985	Malignant cells	NA
MORN4	ENSG00000171160	0.907954	2.75e-10	7.68e-06	0.98	0.903	Malignant cells	NA
VPS36	ENSG00000136100	0.907799	4.34e-07	1.21e-02	0.967	0.843	Malignant cells	NA
SCRN3	ENSG00000144306	0.907255	1.09e-07	3.04e-03	0.86	0.746	Malignant cells	NA
KAT2B	ENSG00000114166	0.902578	2.46e-07	6.89e-03	0.667	0.373	Malignant cells	NA
AAMDC	ENSG00000087884	0.90122	1.51e-11	4.22e-07	0.993	0.978	Malignant cells	NA
YEATS4	ENSG00000127337	0.899814	6.67e-07	1.87e-02	0.927	0.873	Malignant cells	NA
LINC00998	NA	0.898971	5.92e-19	1.66e-14	1	0.933	Malignant cells	NA
AES	NA	0.898901	2.82e-16	7.90e-12	0.993	0.903	Malignant cells	NA
C11orf1	ENSG00000137720	0.898851	4.15e-10	1.16e-05	0.967	0.963	Malignant cells	NA
ROCK2	ENSG00000134318	0.89848	4.02e-10	1.12e-05	1	0.993	Malignant cells	NA
ZBED8	ENSG00000221886	0.897268	2.10e-07	5.86e-03	0.76	0.448	Malignant cells	NA
ADAL	ENSG00000168803	0.8966	7.40e-08	2.07e-03	0.927	0.791	Malignant cells	NA
LINC00920	ENSG00000246898	0.895995	1.40e-06	3.92e-02	0.453	0.201	Malignant cells	NA
CEP19	ENSG00000174007	0.89373	1.06e-06	2.97e-02	0.853	0.687	Malignant cells	NA
SLC35C2	ENSG00000080189	0.893348	2.36e-09	6.59e-05	0.94	0.91	Malignant cells	NA

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Mechanism analysis of drug resistance-related DEGs for each cell type in the pre-treatment samples

Enrichment 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.)

Hallmark, 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.)

Hallmark, 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

Enrichment 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.)

Hallmark, 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.)

Hallmark, 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

This 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

Mechnism	Pval	FDR	Signature	Geneset	Overlap	Background	Cell type	Enriched Genes
Unusual Activation of Pro-survival Pathway	9.80e-06	4.90e-05	2352	781	116	23467	Malignant cells	ADAM9,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 Efflux	1.60e-01	3.60e-01	2352	37	6	23467	Malignant cells	ABCB1,ABCC2,ABCA10,ABCF2,ABCE1,ABCG1
Drug Inactivation by Structure Modification	2.80e-01	3.60e-01	2352	27	4	23467	Malignant cells	GSS,NME1,CMPK1,CYP51A1
Aberration of the Drug's Therapeutic Target	2.90e-01	3.60e-01	2352	90	11	23467	Malignant cells	BRCA1,CDK6,DHFR,EZH2,FGFR1,IL1B,JAK1,COMT,DPP4,MAOA,TOP2A
Epigenetic Alteration of DNA, RNA or Protein	1.00e+00	1.00e+00	2352	455	20	23467	Malignant cells	DNMT1,GSK3B,H2AFY,HOXA13,EIF4G2,SPRY2,TYMS,EZH2,CXCL8,PDCD4,SMC4,TIMP1,SNHG1,LINC00261,GDI2,CDK14,CDR1,MX1,LINC00707,RP11-166P13.3

Hallmark, 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 Hallmark	Up-regulated KEGG	Up-regulated GO BP

Hallmark, 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 Hallmark	Down-regulated KEGG	Down-regulated GO BP

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MicroRNAs (miRNAs) regulating drug resistance-related DEGs for malignant cells

In 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.)

In 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.)

This 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 group	Regulating down-regulated DEGs in resistant group

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Motifs and transcription factors (TFs) regulating drug resistance-related DEGs for each cell type

In 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.)

In 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.)

This 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

motif

NES

AUC

TF_highConf

Cell_type

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Differentially expressed genes act as transcription factors

This table shows the differentially expressed genes that act as transcription factors. (Complete files can be downloaded from the download section.)

TF	motif	Expression	Cell type	Timepoint
KLF13	metacluster_195.2	up	Malignant cells	NA
KLF9	metacluster_195.2	up	Malignant cells	NA
KLF4	metacluster_195.2	up	Malignant cells	NA
KLF7	metacluster_195.2	up	Malignant cells	NA
KLF13	hocomoco__KLF13_HUMAN.H11MO.0.D	up	Malignant cells	NA
KLF13	transfac_pro__M07461	up	Malignant cells	NA
KLF4	transfac_pro__M07461	up	Malignant cells	NA
KLF7	transfac_pro__M07461	up	Malignant cells	NA
KLF9	transfac_pro__M07461	up	Malignant cells	NA
KLF7	metacluster_170.2	up	Malignant cells	NA

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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."