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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
PSAP	ENSG00000197746	-0.287256	5.71e-18	1.05e-13	0.865	0.979	Malignant cells	pre
CYCS	ENSG00000172115	-0.288006	1.38e-21	2.53e-17	0.498	0.746	Malignant cells	pre
C19orf70	NA	-0.288666	2.21e-24	4.05e-20	0.323	0.595	Malignant cells	pre
RPS18	ENSG00000223367	-0.288984	1.19e-26	2.19e-22	1	1	Malignant cells	pre
PDK1	ENSG00000152256	-0.289403	1.83e-20	3.35e-16	0.224	0.443	Malignant cells	pre
SRSF1	ENSG00000136450	-0.289515	2.24e-28	4.12e-24	0.093	0.318	Malignant cells	pre
CREB3L2	ENSG00000182158	-0.290301	7.09e-19	1.30e-14	0.347	0.567	Malignant cells	pre
DNAJB9	ENSG00000128590	-0.293014	1.98e-09	3.63e-05	0.775	0.874	Malignant cells	pre
RPS7	ENSG00000171863	-0.293146	5.25e-30	9.64e-26	0.979	0.981	Malignant cells	pre
SBDS	ENSG00000126524	-0.294158	1.47e-22	2.70e-18	0.306	0.561	Malignant cells	pre
CREB3	ENSG00000107175	-0.294624	1.35e-28	2.49e-24	0.109	0.341	Malignant cells	pre
CD38	ENSG00000004468	-0.295434	3.53e-22	6.47e-18	0.45	0.718	Malignant cells	pre
FAM133A	ENSG00000179083	-0.299313	2.30e-36	4.22e-32	0.052	0.288	Malignant cells	pre
ACY3	ENSG00000132744	-0.299457	2.42e-32	4.45e-28	0.06	0.282	Malignant cells	pre
ZCCHC7	ENSG00000147905	-0.302344	2.08e-29	3.81e-25	0.15	0.408	Malignant cells	pre
PDCD4	ENSG00000150593	-0.30261	2.84e-27	5.21e-23	0.15	0.396	Malignant cells	pre
HLA-E	ENSG00000206493	-0.303043	9.41e-12	1.73e-07	0.708	0.88	Malignant cells	pre
METTL7A	ENSG00000185432	-0.304291	8.42e-24	1.55e-19	0.256	0.507	Malignant cells	pre
RPL36A	ENSG00000241343	-0.305153	6.93e-27	1.27e-22	0.96	0.972	Malignant cells	pre
VPS51	ENSG00000149823	-0.306655	6.75e-26	1.24e-21	0.209	0.461	Malignant cells	pre
LSM4	ENSG00000130520	-0.310554	3.20e-28	5.87e-24	0.187	0.451	Malignant cells	pre
CHST2	ENSG00000175040	-0.312818	2.12e-24	3.88e-20	0.075	0.266	Malignant cells	pre
CD180	ENSG00000134061	-0.315036	2.67e-25	4.89e-21	0.115	0.329	Malignant cells	pre
TMEM11	ENSG00000178307	-0.315071	1.12e-33	2.06e-29	0.12	0.386	Malignant cells	pre
NHP2	ENSG00000145912	-0.315756	1.64e-26	3.02e-22	0.325	0.6	Malignant cells	pre
RPS15A	ENSG00000134419	-0.316282	2.90e-34	5.33e-30	0.996	0.99	Malignant cells	pre
FCRL5	ENSG00000143297	-0.317635	5.99e-23	1.10e-18	0.295	0.53	Malignant cells	pre
MT-CYB	ENSG00000198727	-0.318058	1.13e-17	2.07e-13	0.881	0.981	Malignant cells	pre
CYSTM1	ENSG00000120306	-0.318137	1.94e-33	3.55e-29	0.123	0.388	Malignant cells	pre
SDHA	ENSG00000073578	-0.318387	6.52e-29	1.20e-24	0.137	0.384	Malignant cells	pre
NDUFB5	ENSG00000136521	-0.322139	6.51e-30	1.19e-25	0.215	0.496	Malignant cells	pre
TAF9	ENSG00000276463	-0.323406	3.42e-30	6.28e-26	0.204	0.482	Malignant cells	pre
NDRG1	ENSG00000104419	-0.32517	1.36e-38	2.49e-34	0.039	0.272	Malignant cells	pre
BEX4	ENSG00000102409	-0.325377	5.03e-37	9.24e-33	0.074	0.328	Malignant cells	pre
ZBP1	ENSG00000124256	-0.326675	1.23e-27	2.25e-23	0.275	0.552	Malignant cells	pre
PPA1	ENSG00000180817	-0.326799	1.63e-30	2.99e-26	0.311	0.619	Malignant cells	pre
HINT1	ENSG00000169567	-0.327012	5.54e-27	1.02e-22	0.827	0.942	Malignant cells	pre
TAF7	ENSG00000178913	-0.327804	1.16e-20	2.12e-16	0.268	0.483	Malignant cells	pre
VOPP1	ENSG00000154978	-0.327981	1.42e-25	2.60e-21	0.326	0.588	Malignant cells	pre
LY9	ENSG00000122224	-0.328863	2.16e-30	3.96e-26	0.178	0.448	Malignant cells	pre
FAM174A	ENSG00000174132	-0.330298	1.01e-25	1.86e-21	0.198	0.439	Malignant cells	pre
DNAJB1	ENSG00000132002	-0.331698	1.96e-09	3.59e-05	0.234	0.365	Malignant cells	pre
TMEM109	ENSG00000110108	-0.33304	5.82e-28	1.07e-23	0.225	0.496	Malignant cells	pre
QTRT1	ENSG00000213339	-0.334459	2.56e-31	4.70e-27	0.208	0.489	Malignant cells	pre
SULF2	ENSG00000196562	-0.336636	4.78e-43	8.77e-39	0.027	0.267	Malignant cells	pre
KCNMB2-AS1	ENSG00000237978	-0.338174	1.24e-40	2.27e-36	0.043	0.29	Malignant cells	pre
RPL31	ENSG00000071082	-0.343065	5.30e-29	9.72e-25	0.978	0.987	Malignant cells	pre
TIMD4	ENSG00000145850	-0.343312	7.01e-45	1.38e-40	0.015	0.25	Malignant cells	pre
NDUFS4	ENSG00000164258	-0.344886	2.34e-35	4.28e-31	0.142	0.424	Malignant cells	pre
RPS21	ENSG00000171858	-0.34603	3.45e-31	6.33e-27	0.985	0.987	Malignant 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
CCL4	ENSG00000277943	1.31931	1.17e-37	2.14e-33	0.641	0.351	NK cells	post
GZMH	ENSG00000100450	0.999353	0.00e+00	0.00e+00	0.742	0.439	NK cells	post
JUN	ENSG00000177606	0.976374	2.21e-33	4.06e-29	0.318	0.048	NK cells	post
CCL3	ENSG00000278567	0.934072	9.51e-17	1.74e-12	0.327	0.141	NK cells	post
FOS	ENSG00000170345	0.831329	3.20e-15	5.87e-11	0.298	0.137	NK cells	post
LGALS1	ENSG00000100097	0.799451	4.50e-24	8.25e-20	0.682	0.54	NK cells	post
DUSP1	ENSG00000120129	0.795969	8.58e-17	1.57e-12	0.454	0.277	NK cells	post
RPS4Y1	ENSG00000129824	0.781699	0.00e+00	0.00e+00	0.363	0	NK cells	post
RPS29	ENSG00000213741	0.77818	0.00e+00	0.00e+00	1	0.994	NK cells	post
CD3D	ENSG00000167286	0.73287	3.26e-21	5.98e-17	0.322	0.111	NK cells	post
RPL36A	ENSG00000241343	0.674855	0.00e+00	1.12e-44	0.886	0.702	NK cells	post
FGFBP2	ENSG00000137441	0.546395	2.66e-20	4.89e-16	0.641	0.437	NK cells	post
TRBC1	ENSG00000281981	0.538401	2.19e-18	4.03e-14	0.608	0.429	NK cells	post
RPS17	ENSG00000278229	0.535744	9.37e-32	1.72e-27	0.894	0.758	NK cells	post
IFITM1	ENSG00000185885	0.50252	4.62e-21	8.47e-17	0.721	0.624	NK cells	post
PRF1	ENSG00000180644	0.498595	9.06e-20	1.66e-15	0.87	0.836	NK cells	post
MT2A	ENSG00000125148	0.491188	2.16e-13	3.97e-09	0.636	0.555	NK cells	post
ACTB	ENSG00000075624	0.480447	1.62e-23	2.98e-19	1	1	NK cells	post
UBC	ENSG00000150991	0.46712	1.25e-22	2.30e-18	0.943	0.849	NK cells	post
S100A4	ENSG00000196154	0.451097	5.57e-14	1.02e-09	0.93	0.929	NK cells	post
S100A6	ENSG00000197956	0.426406	1.13e-15	2.08e-11	0.877	0.836	NK cells	post
H1FX	NA	0.420486	1.33e-10	2.43e-06	0.323	0.193	NK cells	post
TRBC2	ENSG00000276849	0.393778	4.85e-11	8.90e-07	0.454	0.33	NK cells	post
MYL12A	ENSG00000101608	0.38986	2.00e-22	3.67e-18	0.952	0.945	NK cells	post
KLF2	ENSG00000127528	0.38985	2.11e-10	3.87e-06	0.447	0.334	NK cells	post
HLA-C	ENSG00000206435	0.384103	1.11e-37	2.04e-33	1	1	NK cells	post
EMP3	ENSG00000142227	0.343465	1.09e-10	2.01e-06	0.751	0.714	NK cells	post
DDIT4	ENSG00000168209	0.334586	2.42e-11	4.43e-07	0.309	0.164	NK cells	post
LINC01871	ENSG00000235576	0.332245	1.69e-07	3.10e-03	0.343	0.239	NK cells	post
SPON2	ENSG00000159674	0.328771	4.75e-07	8.72e-03	0.441	0.317	NK cells	post
EFHD2	ENSG00000142634	0.324347	2.16e-08	3.96e-04	0.571	0.496	NK cells	post
TMA7	ENSG00000232112	0.321369	1.56e-12	2.86e-08	0.845	0.807	NK cells	post
ATP5ME	ENSG00000169020	0.315411	1.88e-08	3.45e-04	0.524	0.443	NK cells	post
CD99	ENSG00000002586	0.314045	1.87e-07	3.43e-03	0.594	0.563	NK cells	post
ABI3	ENSG00000108798	0.312463	7.38e-12	1.35e-07	0.316	0.162	NK cells	post
CD52	ENSG00000169442	0.311567	1.24e-07	2.27e-03	0.937	0.91	NK cells	post
CYBA	ENSG00000051523	0.308869	2.06e-15	3.78e-11	0.984	0.979	NK cells	post
RPS27	ENSG00000177954	0.308168	5.19e-30	9.53e-26	1	1	NK cells	post
CRIP1	ENSG00000213145	0.308131	5.21e-08	9.56e-04	0.398	0.29	NK cells	post
PET100	ENSG00000229833	0.304493	1.06e-07	1.94e-03	0.364	0.267	NK cells	post
NDUFA13	ENSG00000186010	0.292035	4.31e-07	7.91e-03	0.414	0.328	NK cells	post
PTP4A2	ENSG00000184007	0.287577	8.33e-07	1.53e-02	0.47	0.401	NK cells	post
AC114760.2	NA	0.281814	2.20e-06	4.03e-02	0.333	0.239	NK cells	post
SH3BGRL3	ENSG00000142669	0.276781	4.89e-10	8.98e-06	0.972	0.975	NK cells	post
CFL1	ENSG00000172757	0.276464	3.89e-11	7.15e-07	0.977	0.973	NK cells	post
IL32	ENSG00000008517	0.274162	6.04e-07	1.11e-02	0.737	0.609	NK cells	post
PPDPF	ENSG00000125534	0.273904	4.32e-07	7.92e-03	0.745	0.767	NK cells	post
MALAT1	ENSG00000251562	0.267088	8.58e-19	1.57e-14	1	1	NK cells	post
TMSB4X	ENSG00000205542	0.25647	1.77e-28	3.24e-24	1	1	NK cells	post
HLA-A	ENSG00000227715	0.252359	1.56e-19	2.87e-15	0.999	1	NK 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

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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."