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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
	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
	Mechanism analysis of drug resistance-related DEGs for each cell type in the post-treatment samples
	Mechanism analysis of drug resistance-related DEGs for each cell type in one patient or cell lines (This dataset does not contain this module)
	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: GSE161801_PI

Dataset summary for GSE161801_PI

Datast information	Dataset	GSE161801_PI
	PMID	34845188
	Raw data ID/link	EGAD00001006903
	Organism	Homo sapiens
	Source	patients
	Tissue	Bone marrow aspirate
	Cancer type level1	Multiple myeloma
	Cancer type level2	Refractory multiple myeloma (MM)
	Regimen	carfilzomib + dexamethasone
	Drug type	Targeted therapy
	Sample size	pre (resistant 2, sensitive 1); post (resistant 2, sensitive 1)
	Cell number	27674
	Extract protocol	10x genomics
	Data processing	CellRanger 3.0.1
	Public date	Public on Aug 18, 2021
	Description	This dataset has 3 patients with both pre -and post-treatment samples.

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Drug summary for GSE161801_PI

Drug name	DrugBank ID	Drug type	Targets name	Targets uniprot ID
"Carfilzomib"	DB08889	small molecule	PSMB5; PSMB8; PSMB1; PSMB9; PSMB2; PSMB10	P28074; P28062; P20618; P28065; P49721; P40306
"Dexamethasone"	DB01234	small molecule	NR3C1; NR0B1; ANXA1; NOS2; NR1I2	P04150; P51843; P04083; P35228; 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

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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.)

resistant vs. sensitive

Dot plot of significant ligand-receptor pairs in the resistant group	Dot plot of significant ligand-receptor pairs in the sensitive group

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.)

resistant vs. sensitive

Dot plot of significant ligand-receptor pairs in the resistant group	Dot plot of significant ligand-receptor pairs in the sensitive group

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.

Gene symbol	Gene id	avg_log2FC	p_val	p_val_adj	pct.1	pct.2	Cell type	Timepoint
MALAT1	ENSG00000251562	1.13947	0.00e+00	0.00e+00	1	1	NK cells	pre
CCL5	ENSG00000274233	1.0978	1.76e-34	3.23e-30	0.97	0.762	NK cells	pre
FGFBP2	ENSG00000137441	0.985972	3.86e-18	7.08e-14	0.579	0.262	NK cells	pre
CCL4	ENSG00000277943	0.879951	1.03e-19	1.90e-15	0.698	0.331	NK cells	pre
FCGR3A	ENSG00000203747	0.802805	4.51e-17	8.27e-13	0.534	0.234	NK cells	pre
HLA-DPB1	ENSG00000236693	0.670924	3.94e-14	7.23e-10	0.61	0.375	NK cells	pre
GZMH	ENSG00000100450	0.650537	1.09e-16	1.99e-12	0.738	0.419	NK cells	pre
ARPC2	ENSG00000163466	0.589031	1.25e-14	2.29e-10	0.79	0.653	NK cells	pre
S100A6	ENSG00000197956	0.56323	9.12e-15	1.67e-10	0.902	0.706	NK cells	pre
S100A4	ENSG00000196154	0.496187	1.27e-12	2.34e-08	0.979	0.871	NK cells	pre
SPON2	ENSG00000159674	0.463251	2.70e-07	4.95e-03	0.436	0.246	NK cells	pre
ARHGDIB	ENSG00000111348	0.454555	4.71e-11	8.65e-07	0.866	0.77	NK cells	pre
HLA-A	ENSG00000227715	0.452471	2.47e-21	4.53e-17	1	1	NK cells	pre
CALM1	ENSG00000198668	0.450988	8.50e-08	1.56e-03	0.771	0.734	NK cells	pre
DDX6	ENSG00000110367	0.45004	2.00e-06	3.67e-02	0.427	0.278	NK cells	pre
TMSB4X	ENSG00000205542	0.41227	8.03e-25	1.47e-20	1	1	NK cells	pre
ZEB2	ENSG00000169554	0.408404	1.32e-06	2.42e-02	0.399	0.234	NK cells	pre
CYBA	ENSG00000051523	0.369771	6.25e-10	1.15e-05	0.976	0.907	NK cells	pre
CST7	ENSG00000077984	0.366875	5.44e-08	9.99e-04	0.851	0.871	NK cells	pre
ADGRG1	ENSG00000205336	0.357543	7.66e-10	1.41e-05	0.287	0.081	NK cells	pre
B2M	ENSG00000273686	0.329525	1.69e-21	3.10e-17	1	1	NK cells	pre
ACTB	ENSG00000075624	0.329313	3.55e-07	6.51e-03	1	1	NK cells	pre
FTL	ENSG00000087086	0.310526	4.32e-08	7.93e-04	0.985	0.944	NK cells	pre
PFN1	ENSG00000108518	0.286449	2.33e-06	4.27e-02	0.997	1	NK cells	pre
HLA-C	ENSG00000206435	0.275347	1.45e-07	2.66e-03	1	0.996	NK cells	pre
NFKBIZ	ENSG00000144802	-0.256657	7.37e-10	1.35e-05	0.07	0.258	NK cells	pre
TXK	ENSG00000074966	-0.257585	2.48e-07	4.55e-03	0.143	0.323	NK cells	pre
RPL15	ENSG00000174748	-0.257849	9.62e-08	1.77e-03	1	1	NK cells	pre
RPS27A	ENSG00000143947	-0.25797	3.25e-10	5.97e-06	1	1	NK cells	pre
RPL18A	ENSG00000105640	-0.260952	4.25e-10	7.80e-06	1	1	NK cells	pre
PIM3	ENSG00000198355	-0.262	6.21e-08	1.14e-03	0.104	0.278	NK cells	pre
DAZAP2	ENSG00000183283	-0.269127	1.20e-06	2.19e-02	0.296	0.508	NK cells	pre
EIF3L	ENSG00000100129	-0.269547	1.10e-07	2.01e-03	0.21	0.431	NK cells	pre
DNAJA1	ENSG00000086061	-0.27043	9.05e-10	1.66e-05	0.155	0.399	NK cells	pre
POLR2K	ENSG00000147669	-0.271778	1.47e-06	2.70e-02	0.213	0.395	NK cells	pre
CNN2	ENSG00000064666	-0.277471	1.67e-09	3.06e-05	0.098	0.298	NK cells	pre
CD320	ENSG00000167775	-0.278549	2.70e-10	4.95e-06	0.076	0.274	NK cells	pre
NDUFS5	ENSG00000168653	-0.279572	9.56e-08	1.75e-03	0.253	0.488	NK cells	pre
TCF7	ENSG00000081059	-0.283419	9.75e-12	1.79e-07	0.061	0.266	NK cells	pre
XBP1	ENSG00000100219	-0.285457	4.18e-07	7.68e-03	0.305	0.544	NK cells	pre
BTG2	ENSG00000159388	-0.287032	4.26e-09	7.82e-05	0.183	0.423	NK cells	pre
WDR83OS	ENSG00000105583	-0.290085	2.95e-07	5.41e-03	0.314	0.54	NK cells	pre
SMDT1	ENSG00000274112	-0.290787	5.77e-10	1.06e-05	0.168	0.419	NK cells	pre
RPL12	ENSG00000197958	-0.291571	2.64e-09	4.84e-05	0.994	1	NK cells	pre
RPL7A	ENSG00000280858	-0.293999	2.20e-08	4.04e-04	0.927	0.98	NK cells	pre
ACAP1	ENSG00000288169	-0.295103	1.62e-08	2.98e-04	0.18	0.403	NK cells	pre
RPL7	ENSG00000147604	-0.29644	6.57e-08	1.21e-03	1	1	NK cells	pre
RPL26	ENSG00000161970	-0.297987	1.44e-10	2.63e-06	1	1	NK cells	pre
NFE2L2	ENSG00000116044	-0.298615	5.50e-13	1.01e-08	0.073	0.306	NK cells	pre
LTB	ENSG00000223448	-0.301384	2.60e-08	4.78e-04	0.101	0.286	NK cells	pre

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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.

Gene symbol	Gene id	avg_log2FC	p_val	p_val_adj	pct.1	pct.2	Cell type	Timepoint
MT-ND5	ENSG00000198786	-0.680806	1.48e-39	2.72e-35	0.751	0.941	Malignant cells	post
NDUFA1	ENSG00000125356	-0.685013	0.00e+00	4.20e-45	0.617	0.917	Malignant cells	post
MT-CO2	ENSG00000198712	-0.706422	2.53e-39	4.64e-35	0.979	0.996	Malignant cells	post
CD47	ENSG00000196776	-0.709906	0.00e+00	0.00e+00	0.275	0.748	Malignant cells	post
ATP5MF	ENSG00000241468	-0.716742	0.00e+00	0.00e+00	0.542	0.909	Malignant cells	post
CKLF	ENSG00000217555	-0.72014	0.00e+00	0.00e+00	0.162	0.618	Malignant cells	post
UQCR11	ENSG00000127540	-0.723563	0.00e+00	0.00e+00	0.687	0.969	Malignant cells	post
RPL38	ENSG00000172809	-0.723565	0.00e+00	0.00e+00	0.957	1	Malignant cells	post
SVIP	ENSG00000198168	-0.727575	6.35e-43	1.17e-38	0.335	0.709	Malignant cells	post
UBL5	ENSG00000198258	-0.739058	1.82e-44	3.38e-40	0.599	0.949	Malignant cells	post
RPL35A	ENSG00000182899	-0.758009	0.00e+00	0.00e+00	0.991	1	Malignant cells	post
RPL15	ENSG00000174748	-0.760749	0.00e+00	0.00e+00	0.999	1	Malignant cells	post
NDUFA2	ENSG00000131495	-0.767848	0.00e+00	0.00e+00	0.263	0.756	Malignant cells	post
TXN	ENSG00000136810	-0.771642	0.00e+00	0.00e+00	0.52	0.937	Malignant cells	post
CALM2	ENSG00000143933	-0.775124	4.90e-42	8.98e-38	0.518	0.87	Malignant cells	post
TSTD1	ENSG00000215845	-0.779924	0.00e+00	0.00e+00	0.286	0.78	Malignant cells	post
RPL10	ENSG00000147403	-0.789702	0.00e+00	0.00e+00	1	1	Malignant cells	post
TIMD4	ENSG00000145850	-0.807314	0.00e+00	0.00e+00	0.013	0.378	Malignant cells	post
TNFRSF13B	ENSG00000240505	-0.814057	0.00e+00	0.00e+00	0.14	0.661	Malignant cells	post
SLC25A5	ENSG00000005022	-0.823626	0.00e+00	0.00e+00	0.369	0.819	Malignant cells	post
RPL32	ENSG00000144713	-0.835943	0.00e+00	0.00e+00	0.998	1	Malignant cells	post
NDUFA4	ENSG00000189043	-0.844992	0.00e+00	0.00e+00	0.722	0.937	Malignant cells	post
COX11	ENSG00000166260	-0.849844	0.00e+00	0.00e+00	0.074	0.583	Malignant cells	post
H3F3A	NA	-0.873256	0.00e+00	0.00e+00	0.692	0.949	Malignant cells	post
RPS28	ENSG00000233927	-0.885365	0.00e+00	0.00e+00	0.998	1	Malignant cells	post
SEC61G	ENSG00000132432	-0.899854	0.00e+00	0.00e+00	0.78	0.969	Malignant cells	post
LAMP5	ENSG00000125869	-0.904764	0.00e+00	0.00e+00	0.248	0.768	Malignant cells	post
HLA-B	ENSG00000206450	-0.918268	2.47e-39	4.53e-35	0.978	0.984	Malignant cells	post
SSR4	ENSG00000180879	-0.918874	0.00e+00	0.00e+00	0.989	1	Malignant cells	post
RPS14	ENSG00000164587	-0.921478	0.00e+00	0.00e+00	0.999	1	Malignant cells	post
RPS23	ENSG00000186468	-0.923835	0.00e+00	0.00e+00	0.99	1	Malignant cells	post
RPL24	ENSG00000114391	-0.924011	0.00e+00	0.00e+00	0.957	0.996	Malignant cells	post
RPL26	ENSG00000161970	-0.94065	1.40e-45	3.57e-41	0.961	0.976	Malignant cells	post
VIM	ENSG00000026025	-0.957874	0.00e+00	0.00e+00	0.244	0.803	Malignant cells	post
CCR10	ENSG00000184451	-0.961272	0.00e+00	0.00e+00	0.202	0.654	Malignant cells	post
RPL37	ENSG00000145592	-0.966673	0.00e+00	0.00e+00	0.988	1	Malignant cells	post
CIRBP	ENSG00000099622	-0.976265	0.00e+00	0.00e+00	0.561	0.957	Malignant cells	post
CADM1	ENSG00000182985	-1.01096	0.00e+00	0.00e+00	0.065	0.677	Malignant cells	post
SPCS1	ENSG00000114902	-1.02284	0.00e+00	0.00e+00	0.855	0.992	Malignant cells	post
RPL36A	ENSG00000241343	-1.04322	0.00e+00	0.00e+00	0.942	1	Malignant cells	post
SUB1	ENSG00000113387	-1.07449	0.00e+00	0.00e+00	0.97	1	Malignant cells	post
RPS27	ENSG00000177954	-1.09065	0.00e+00	0.00e+00	0.999	1	Malignant cells	post
TOMM7	ENSG00000196683	-1.10857	0.00e+00	0.00e+00	0.718	0.98	Malignant cells	post
COX7C	ENSG00000127184	-1.13163	0.00e+00	0.00e+00	0.861	1	Malignant cells	post
RPL39	ENSG00000198918	-1.1836	0.00e+00	0.00e+00	0.993	1	Malignant cells	post
ACTB	ENSG00000075624	-1.20642	0.00e+00	1.40e-45	0.766	0.949	Malignant cells	post
HLA-C	ENSG00000206435	-1.29569	0.00e+00	0.00e+00	0.98	1	Malignant cells	post
TIMP1	ENSG00000102265	-1.3968	0.00e+00	0.00e+00	0.132	0.642	Malignant cells	post
RPL17	ENSG00000265681	-1.47249	0.00e+00	0.00e+00	0.731	0.984	Malignant cells	post
IGLL5	ENSG00000254709	-1.62241	0.00e+00	0.00e+00	0.205	0.945	Malignant cells	post

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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.

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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.)

Enrichment results for 5 known drug-resistant mechanisms in malignant cells

Mechnism	Pval	FDR	Signature	Geneset	Overlap	Background	Cell type	Enriched Genes
Unusual Activation of Pro-survival Pathway	1.00e-04	5.00e-04	593	781	38	23467	Malignant cells	ANXA2,CDKN1A,CFLAR,IDH2,IFI27,JUN,MCL1,RPS6,S100A4,VOPP1,YWHAZ,SLC25A5,BTG1,CCND1,CCNG1,CD44,CXCR4,DUSP1,EGR1,HSP90B1,EZR,FTL,GAPDH,GAS6,HSPA8,EIF4E,NFKBIA,LDHA,MTDH,PABPC1,PDCD4,RAP1B,HNRNPA1,TPT1,TNFSF10,YBX1,GNAS,NPM1
Aberration of the Drug's Therapeutic Target	4.00e-01	1.00e+00	593	90	3	23467	Malignant cells	IDH2,NPM1,LAG3
Irregularity in Drug Uptake and Drug Efflux	6.10e-01	1.00e+00	593	37	1	23467	Malignant cells	SLC7A5
Epigenetic Alteration of DNA, RNA or Protein	8.90e-01	1.00e+00	593	455	8	23467	Malignant cells	IDH2,LMNA,PMAIP1,CXCR4,GAPDH,PDCD4,CYTOR,MT-CO2
Drug Inactivation by Structure Modification	1.00e+00	1.00e+00	593	27	0	23467	Malignant cells

Enrichment results for 1 known drug resistance mechanisms in TME cells

Mechnism	Pval	FDR	Signature	Geneset	Overlap	Background	Cell type	Enriched Genes
Regulation by the Disease Microenvironment	1.00e+00	1.00e+00	101	186	0	23467	B cells	NA
Regulation by the Disease Microenvironment	2.60e-01	2.60e-01	37	186	1	23467	CD4+ T cells	MALAT1
Regulation by the Disease Microenvironment	9.80e-03	9.80e-03	105	186	4	23467	CD8+ T cells	TGFB1,CXCR4,VIM,MALAT1
Regulation by the Disease Microenvironment	1.80e-01	1.80e-01	25	186	1	23467	cDCs	MALAT1
Regulation by the Disease Microenvironment	8.00e-03	8.00e-03	155	186	5	23467	Mono_Macro	ZEB2,IL1B,RHOB,VIM,MALAT1
Regulation by the Disease Microenvironment	4.20e-01	4.20e-01	180	186	2	23467	NK cells	ZEB2,MALAT1

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.)

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

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.)

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

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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.)

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	2.00e-06	1.00e-05	537	781	40	23467	Malignant cells	ADAM10,CDKN1A,GSTP1,IDH2,IFI27,ISG15,JUN,MYC,RHOA,VOPP1,YWHAZ,SLC25A5,HSPA5,BTG1,CCND1,HSPD1,CLTC,CXCR4,DUSP1,HSP90B1,EZR,FOXO3,GAS6,HAX1,HMGB2,HSPA8,NFKBIA,MTDH,PABPC1,HNRNPA1,S100A11,SRI,TPT1,ENO1,CALR,NPM1,EIF4EBP1,RCN1,HSH2D,APP
Drug Inactivation by Structure Modification	4.60e-01	6.10e-01	537	27	1	23467	Malignant cells	GSTP1
Epigenetic Alteration of DNA, RNA or Protein	4.70e-01	6.10e-01	537	455	11	23467	Malignant cells	IDH2,PMAIP1,CXCR4,FOXO3,TIMP1,CYTOR,MALAT1,PPP1R15A,MT-CO2,MX1,GABPB1-AS1
Irregularity in Drug Uptake and Drug Efflux	5.80e-01	6.10e-01	537	37	1	23467	Malignant cells	ABCB9
Aberration of the Drug's Therapeutic Target	6.10e-01	6.10e-01	537	90	2	23467	Malignant cells	IDH2,NPM1

Enrichment results for 1 known drug resistance mechanisms in TME cells

Mechnism	Pval	FDR	Signature	Geneset	Overlap	Background	Cell type	Enriched Genes
Regulation by the Disease Microenvironment	8.40e-02	8.40e-02	61	186	2	23467	B cells	CXCR4,MALAT1
Regulation by the Disease Microenvironment	1.00e+00	1.00e+00	32	186	0	23467	CD4+ T cells	NA
Regulation by the Disease Microenvironment	1.00e+00	1.00e+00	121	186	0	23467	CD8+ T cells	NA
Regulation by the Disease Microenvironment	6.60e-02	6.60e-02	53	186	2	23467	cDCs	CXCR4,VIM
Regulation by the Disease Microenvironment	7.10e-02	7.10e-02	196	186	4	23467	Mono_Macro	CXCR4,RHOB,VIM,MALAT1
Regulation by the Disease Microenvironment	7.40e-01	7.40e-01	167	186	1	23467	NK cells	MALAT1

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.)

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

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.)

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

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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.)

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.)

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.)

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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.)

Regulating up-regulated DEGs in resistant group	Regulating down-regulated DEGs in resistant group

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.)

Regulating up-regulated DEGs in resistant group	Regulating down-regulated DEGs in resistant group

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.)

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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.)

Motifs and TFs regulating up-regulated DEGs in resistant group of the pre-treatment samples

motif	motif	NES	AUC	TF_highConf	Cell_type
	transfac_pro__M05939	13.8	0.495	ZNF471 (directAnnotation).	CD4+ T cells
	transfac_pro__M04950	8.23	0.302	EGR1 (directAnnotation).	CD4+ T cells
	transfac_pro__M06362	7.27	0.268	ZNF730 (directAnnotation).	CD4+ T cells
	transfac_pro__M06267	6.1	0.228	ZNF805 (directAnnotation).	CD4+ T cells
	swissregulon__hs__SPI1	6.02	0.225	SPI1 (directAnnotation).	CD4+ T cells
	transfac_pro__M06339	5.81	0.217	ZNF425 (directAnnotation).	CD4+ T cells
	transfac_pro__M06411	5.77	0.216	ZNF662 (directAnnotation).	CD4+ T cells
	taipale_tf_pairs__SOX6_TBX21_RGGTGTNNNNNNNNNYATTGT_CAP_repr	5.68	0.213	SOX6; TBX21 (directAnnotation).	CD4+ T cells
	metacluster_167.7	5.6	0.21	IRF8 (inferredBy_Orthology).	CD4+ T cells
	transfac_pro__M05392	5.59	0.21	SCRT2 (inferredBy_Orthology).	CD4+ T cells

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Motifs and TFs regulating down-regulated DEGs in resistant group of the pre-treatment samples

motif	motif	NES	AUC	TF_highConf	Cell_type
	metacluster_107.2	6.66	0.107	CERS2; CERS3; CERS4; CERS5; CERS6 (inferredBy_Orthology).	B cells
	metacluster_107.1	4.29	0.078	CERS2; CERS3; CERS4; CERS5; CERS6 (inferredBy_Orthology).	B cells
	metacluster_141.13	4.21	0.077	METTL14 (inferredBy_Orthology).	B cells
	kznf__ZNF777_Imbeault2017_OM_MEME	4.08	0.0754	ZNF777 (directAnnotation).	B cells
	metacluster_119.2	4.01	0.0746	CCNT2; GATA1; GATA1; GATA1; GATA1; GATA2; GATA2; GATA2; NCOA1; TAL1; TAL1; TAL1; TAL1; ZNF823 (directAnnotation). GATA1; TAL1; TAL1; TAL1; TAL1 (inferredBy_Orthology).	B cells
	jaspar__MA1957.1	4	0.0745	ELK1 (directAnnotation).	B cells
	taipale_tf_pairs__FOXJ2_ELF1_RMAGAAAACCGAANN_CAP_repr	3.83	0.0724	ELF1; FOXJ2 (directAnnotation).	B cells
	transfac_pro__M05521	3.75	0.0713	ZNF398 (directAnnotation).	B cells
	metacluster_72.10	3.66	0.0702	ZNF697 (directAnnotation).	B cells
	hocomoco__MEIS2_HUMAN.H11MO.0.B	3.61	0.0697	MEIS2 (directAnnotation).	B cells

Page: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49

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.)

Motifs and TFs regulating up-regulated DEGs in resistant group of the post-treatment samples

motif	motif	NES	AUC	TF_highConf	Cell_type
	taipale_tf_pairs__TEAD4_DLX2_NRCATTCNNNNYAATTN_CAP_repr	6.41	0.253	DLX2; TEAD4 (directAnnotation).	B cells
	taipale_tf_pairs__ELK1_TBX21_TNRCACCGGAAGNN_CAP	6.3	0.249	ELK1; TBX21 (directAnnotation).	B cells
	taipale_tf_pairs__HOXB2_NHLH1_NYMATTANNNNNNCAGCTGNN_CAP_repr	6.24	0.247	HOXB2; NHLH1 (directAnnotation).	B cells
	yetfasco__TBP-TFIIB_1329	6.11	0.242	GTF2B; TBPL2 (inferredBy_Orthology).	B cells
	transfac_pro__M00979	5.9	0.234	PAX6 (directAnnotation).	B cells
	transfac_pro__M04855	5.8	0.23	IRF4 (directAnnotation).	B cells
	transfac_pro__M05694	5.67	0.226	ZNF80 (directAnnotation).	B cells
	taipale_cyt_meth__ZNF396_NTGTMCRAAAN_FL_meth_repr	5.55	0.221	ZNF396 (directAnnotation).	B cells
	transfac_pro__M05901	5.37	0.215	ZNF561 (directAnnotation).	B cells
	kznf__ZFP90_Imbeault2017_RP_RCADE	5.32	0.213	ZFP90 (directAnnotation).	B cells

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Motifs and TFs regulating down-regulated DEGs in resistant group of the post-treatment samples

motif	motif	NES	AUC	TF_highConf	Cell_type
	transfac_pro__M04761	5.12	0.128	HSF1 (directAnnotation).	B cells
	jaspar__MA1125.1	4.45	0.115	ZNF384 (directAnnotation).	B cells
	taipale_tf_pairs__PBX4_HOXA10_CCATAAATCA_CAP	4.43	0.114	HOXA10; PBX4 (directAnnotation).	B cells
	metacluster_144.10	4.04	0.107	ZNF100 (directAnnotation).	B cells
	taipale_tf_pairs__ERF_SREBF2_NNCACGTGACMGGAARNN_CAP_repr	4.04	0.107	ERF; SREBF2 (directAnnotation).	B cells
	hocomoco__CPEB1_HUMAN.H11MO.0.D	4.04	0.107	CPEB1 (directAnnotation).	B cells
	kznf__ZNF384_Schmitges2016_RCADE	3.97	0.106	ZNF384 (directAnnotation).	B cells
	taipale_cyt_meth__PITX2_YTAATCCN_FL	3.97	0.106	PITX2 (directAnnotation).	B cells
	metacluster_0.5	3.81	0.102	ZNF264 (directAnnotation).	B cells
	metacluster_46.5	3.64	0.0991	HLF; TEF (directAnnotation).	B cells

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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.)

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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
ARID3A	tfdimers__MD00423	down	B cells	post
SND1	hdpi__SND1	down	B cells	post
FOS	jaspar__MA1951.1	up	CD4+ T cells	post
JUNB	metacluster_111.4	up	CD4+ T cells	post
FOS	metacluster_111.4	up	CD4+ T cells	post
FOS	metacluster_148.1	up	CD4+ T cells	post
JUNB	metacluster_148.1	up	CD4+ T cells	post
FOS	metacluster_157.2	up	CD4+ T cells	post
JUNB	metacluster_157.2	up	CD4+ T cells	post
FOS	jaspar__MA1951.1	up	CD8+ T cells	post

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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."