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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
	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_IMiD

Dataset summary for GSE161801_IMiD

Datast information	Dataset	GSE161801_IMiD
	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	pomalidomide + dexamethasone OR lenalidomide + dexamethasone
	Drug type	Targeted therapy
	Sample size	pre (resistant 6, sensitive 2); post (resistant 6, sensitive 3)
	Cell number	85449
	Extract protocol	10x genomics
	Data processing	CellRanger 3.0.1
	Public date	Public on Aug 18, 2021
	Description	This dataset has 9 patients, 8 of whom have both pre- and post-treatment samples.

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Drug summary for GSE161801_IMiD

Drug name	DrugBank ID	Drug type	Targets name	Targets uniprot ID
"Pomalidomide"	DB08910	small molecule	CRBN; TNF; PTGS2	Q96SW2; P01375; P35354
"Lenalidomide"	DB00480	small molecule	CRBN; TNFSF11; CDH5; PTGS2	Q96SW2; O14788; P33151; P35354
"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
RPS29	ENSG00000213741	0.758832	1.50e-08	3.23e-04	1	1	Progenitors	pre
RPS27	ENSG00000177954	0.619682	3.00e-09	6.48e-05	1	1	Progenitors	pre
RPL21	ENSG00000122026	0.402707	1.58e-06	3.40e-02	1	1	Progenitors	pre
MED24	ENSG00000008838	-0.309381	1.74e-06	3.76e-02	0.057	0.31	Progenitors	pre
EIF4G1	ENSG00000114867	-0.33801	1.79e-06	3.87e-02	0.084	0.379	Progenitors	pre
MCM2	ENSG00000073111	-0.434386	1.66e-07	3.58e-03	0.186	0.621	Progenitors	pre
MCM4	ENSG00000104738	-0.470327	2.14e-06	4.61e-02	0.196	0.586	Progenitors	pre
C8orf59	NA	-0.562311	9.14e-07	1.97e-02	0.287	0.69	Progenitors	pre
RAN	ENSG00000132341	-0.566532	1.24e-06	2.67e-02	0.838	1	Progenitors	pre
SRSF7	ENSG00000115875	-0.611735	7.14e-07	1.54e-02	0.541	0.862	Progenitors	pre
HSPA1A	ENSG00000237724	-0.682446	2.02e-09	4.36e-05	0.057	0.379	Progenitors	pre
MT-ND1	ENSG00000198888	-0.796411	8.31e-07	1.79e-02	0.99	0.966	Progenitors	pre
EIF5A	ENSG00000288145	-1.11987	1.03e-09	2.23e-05	0.493	0.966	Progenitors	pre
RPS29	ENSG00000213741	0.856987	1.90e-06	4.10e-02	1	1	pDCs	pre
S100A8	ENSG00000143546	0.798576	0.00e+00	0.00e+00	0.557	0.256	NK cells	pre
S100A9	ENSG00000163220	0.665535	0.00e+00	1.87e-42	0.571	0.372	NK cells	pre
LYZ	ENSG00000090382	0.584628	3.25e-38	7.01e-34	0.471	0.262	NK cells	pre
FCER1G	ENSG00000158869	0.536322	0.00e+00	8.06e-42	0.852	0.622	NK cells	pre
MT-ND3	ENSG00000198840	0.507877	0.00e+00	0.00e+00	0.992	0.996	NK cells	pre
GZMB	ENSG00000100453	0.504181	3.63e-29	7.83e-25	0.941	0.92	NK cells	pre
RPL36A	ENSG00000241343	0.483367	4.02e-31	8.69e-27	0.827	0.755	NK cells	pre
AREG	ENSG00000109321	0.481522	4.57e-20	9.86e-16	0.391	0.229	NK cells	pre
KLRC1	ENSG00000134545	0.453534	6.75e-30	1.46e-25	0.495	0.266	NK cells	pre
RPS29	ENSG00000213741	0.433209	0.00e+00	0.00e+00	1	0.999	NK cells	pre
SELL	ENSG00000188404	0.413903	2.03e-11	4.38e-07	0.406	0.301	NK cells	pre
NEAT1	ENSG00000245532	0.402484	2.60e-22	5.62e-18	0.813	0.752	NK cells	pre
CST3	ENSG00000101439	0.376166	1.06e-23	2.30e-19	0.363	0.192	NK cells	pre
RPS17	ENSG00000278229	0.358455	5.55e-26	1.20e-21	0.933	0.889	NK cells	pre
UQCR11	ENSG00000127540	0.354233	3.25e-21	7.02e-17	0.751	0.671	NK cells	pre
CDC42SE1	ENSG00000197622	0.34636	2.16e-07	4.65e-03	0.47	0.411	NK cells	pre
ATP5ME	ENSG00000169020	0.331333	9.74e-15	2.10e-10	0.585	0.515	NK cells	pre
POLR2L	ENSG00000177700	0.330751	5.38e-17	1.16e-12	0.686	0.616	NK cells	pre
ATP5MPL	NA	0.31756	2.50e-19	5.41e-15	0.756	0.711	NK cells	pre
S100A11	ENSG00000163191	0.301527	5.25e-10	1.13e-05	0.594	0.549	NK cells	pre
ISG15	ENSG00000187608	0.294403	1.60e-08	3.45e-04	0.389	0.31	NK cells	pre
TYROBP	ENSG00000011600	0.282584	2.45e-20	5.28e-16	0.928	0.863	NK cells	pre
IFITM3	ENSG00000142089	0.279445	5.23e-09	1.13e-04	0.325	0.234	NK cells	pre
CYCS	ENSG00000172115	-0.252316	4.92e-15	1.06e-10	0.406	0.581	NK cells	pre
C12orf57	ENSG00000111678	-0.252612	1.76e-22	3.79e-18	0.24	0.427	NK cells	pre
LDHA	ENSG00000288299	-0.253494	2.85e-18	6.16e-14	0.375	0.566	NK cells	pre
NACA	ENSG00000196531	-0.25368	2.29e-21	4.95e-17	0.944	0.978	NK cells	pre
CD160	ENSG00000117281	-0.254097	1.39e-22	3.00e-18	0.118	0.254	NK cells	pre
CNBP	ENSG00000169714	-0.254286	3.04e-21	6.56e-17	0.361	0.569	NK cells	pre
SBDS	ENSG00000126524	-0.256803	2.42e-27	5.23e-23	0.159	0.334	NK cells	pre
HSPA5	ENSG00000044574	-0.257855	2.84e-18	6.14e-14	0.383	0.564	NK cells	pre
DHRS7	ENSG00000100612	-0.259852	1.15e-21	2.49e-17	0.327	0.512	NK cells	pre
PPIA	ENSG00000196262	-0.259932	8.82e-17	1.90e-12	0.796	0.864	NK cells	pre
PDIA3	ENSG00000167004	-0.261081	1.27e-19	2.74e-15	0.508	0.703	NK cells	pre
RAC2	ENSG00000128340	-0.261161	1.78e-14	3.84e-10	0.611	0.746	NK cells	pre
TSC22D3	ENSG00000157514	-0.261682	1.87e-07	4.04e-03	0.652	0.743	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
AC245014.3	NA	0.303808	2.18e-09	4.71e-05	0.286	0.151	NK cells	post
ISG20	ENSG00000172183	0.29919	1.13e-07	2.44e-03	0.512	0.369	NK cells	post
PSMA4	ENSG00000041357	0.291505	6.17e-10	1.33e-05	0.454	0.299	NK cells	post
ID2	ENSG00000115738	0.289568	9.07e-07	1.96e-02	0.819	0.768	NK cells	post
YPEL3	ENSG00000090238	0.284322	1.23e-11	2.66e-07	0.299	0.147	NK cells	post
MTRNR2L8	NA	0.283927	5.85e-09	1.26e-04	0.498	0.341	NK cells	post
CST3	ENSG00000101439	0.282227	2.30e-10	4.97e-06	0.41	0.256	NK cells	post
TYMP	ENSG00000025708	0.277943	2.37e-10	5.11e-06	0.258	0.122	NK cells	post
TYROBP	ENSG00000011600	0.269265	1.22e-08	2.62e-04	0.857	0.795	NK cells	post
GIMAP7	ENSG00000179144	0.265415	1.65e-09	3.55e-05	0.396	0.25	NK cells	post
XBP1	ENSG00000100219	0.252603	1.39e-08	3.00e-04	0.613	0.461	NK cells	post
IFITM3	ENSG00000142089	0.251589	6.03e-09	1.30e-04	0.35	0.209	NK cells	post
RPL36A	ENSG00000241343	0.251267	1.42e-10	3.06e-06	0.911	0.78	NK cells	post
CD300A	ENSG00000167851	0.250142	1.49e-08	3.22e-04	0.372	0.241	NK cells	post
BTG1	ENSG00000133639	-0.251892	5.37e-09	1.16e-04	0.879	0.911	NK cells	post
ACTB	ENSG00000075624	-0.255443	3.18e-10	6.87e-06	1	1	NK cells	post
C12orf75	ENSG00000235162	-0.257431	9.48e-08	2.05e-03	0.512	0.627	NK cells	post
GADD45B	ENSG00000099860	-0.257703	5.74e-08	1.24e-03	0.235	0.348	NK cells	post
MT-ATP6	ENSG00000198899	-0.262354	5.46e-11	1.18e-06	0.99	0.996	NK cells	post
XIST	ENSG00000229807	-0.263142	4.59e-16	9.90e-12	0.115	0.275	NK cells	post
LITAF	ENSG00000189067	-0.265436	5.00e-08	1.08e-03	0.526	0.65	NK cells	post
MT-CYB	ENSG00000198727	-0.273637	3.11e-10	6.71e-06	0.989	0.994	NK cells	post
AC114760.2	NA	-0.273924	7.30e-11	1.58e-06	0.17	0.301	NK cells	post
PTMA	ENSG00000187514	-0.277523	1.60e-18	3.45e-14	0.998	1	NK cells	post
HLA-DQB1	ENSG00000206237	-0.277541	8.18e-14	1.77e-09	0.139	0.288	NK cells	post
YPEL5	ENSG00000119801	-0.2788	1.89e-08	4.07e-04	0.248	0.365	NK cells	post
IL32	ENSG00000008517	-0.286336	5.94e-08	1.28e-03	0.566	0.718	NK cells	post
CYCS	ENSG00000172115	-0.295983	3.43e-10	7.40e-06	0.387	0.518	NK cells	post
EIF5A	ENSG00000288145	-0.298988	4.15e-12	8.96e-08	0.306	0.467	NK cells	post
ITGB1	ENSG00000150093	-0.300346	1.11e-07	2.40e-03	0.421	0.525	NK cells	post
HLA-DRA	ENSG00000277263	-0.337192	1.02e-06	2.21e-02	0.529	0.586	NK cells	post
CD3G	ENSG00000160654	-0.342744	1.58e-19	3.42e-15	0.116	0.294	NK cells	post
PNRC1	ENSG00000146278	-0.357684	4.77e-13	1.03e-08	0.496	0.621	NK cells	post
SSR4	ENSG00000180879	-0.368387	5.14e-11	1.11e-06	0.894	0.917	NK cells	post
DDX5	ENSG00000108654	-0.383362	4.00e-23	8.63e-19	0.927	0.968	NK cells	post
GZMH	ENSG00000100450	-0.392524	1.17e-13	2.52e-09	0.644	0.793	NK cells	post
HLA-DRB1	ENSG00000228080	-0.421233	5.23e-13	1.13e-08	0.427	0.573	NK cells	post
HLA-C	ENSG00000206435	-0.428343	1.26e-44	2.84e-40	1	1	NK cells	post
TRGC2	ENSG00000227191	-0.43545	1.90e-10	4.10e-06	0.258	0.392	NK cells	post
UBC	ENSG00000150991	-0.437066	5.47e-34	1.18e-29	0.952	0.994	NK cells	post
CXCR4	ENSG00000121966	-0.454986	2.19e-20	4.72e-16	0.585	0.761	NK cells	post
PPP2R5C	ENSG00000078304	-0.486251	2.83e-18	6.10e-14	0.476	0.64	NK cells	post
RGS1	ENSG00000090104	-0.490811	1.99e-23	4.29e-19	0.14	0.347	NK cells	post
PMAIP1	ENSG00000141682	-0.496528	8.08e-26	1.74e-21	0.149	0.369	NK cells	post
LYAR	ENSG00000145220	-0.505457	1.65e-22	3.57e-18	0.293	0.512	NK cells	post
CD69	ENSG00000110848	-0.525409	8.96e-29	1.93e-24	0.439	0.685	NK cells	post
HLA-DPB1	ENSG00000236693	-0.5525	8.09e-27	1.75e-22	0.401	0.631	NK cells	post
AC020916.1	NA	-0.584361	1.39e-34	3.00e-30	0.096	0.331	NK cells	post
KLF6	ENSG00000067082	-0.595023	1.14e-33	2.45e-29	0.327	0.608	NK cells	post
CCL5	ENSG00000274233	-0.597437	1.02e-40	2.21e-36	0.894	0.979	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	1.70e-12	8.50e-12	486	781	50	23467	Malignant cells	ANXA2,AREG,BCL2L11,FBXW7,GSTP1,HMGB1,IFI27,ISG15,JUN,MCL1,RHOA,S100A4,STMN1,TP53INP1,VOPP1,YWHAZ,SLC25A5,HSPA5,BMI1,CCND1,CCNG1,HSPD1,CXCR4,DUSP1,DUSP2,EGR1,HSP90B1,FTL,GAPDH,HMGB2,HSPA8,NFKBIA,MTDH,MDM4,NSD2,NUCKS1,PABPC1,RAC1,HNRNPA1,S100A11,SIAH2,TPT1,UCP2,YBX1,CALR,FGFR3,NPM1,MDK,RCN1,PMVK
Epigenetic Alteration of DNA, RNA or Protein	1.50e-01	3.80e-01	486	455	13	23467	Malignant cells	BCL2L11,FBXW7,LMNA,PMAIP1,BMI1,CXCR4,GAPDH,TIMP1,CYTOR,MALAT1,PPP1R15A,MT-CO2,MX1
Drug Inactivation by Structure Modification	4.30e-01	5.60e-01	486	27	1	23467	Malignant cells	GSTP1
Irregularity in Drug Uptake and Drug Efflux	5.40e-01	5.60e-01	486	37	1	23467	Malignant cells	ABCB9
Aberration of the Drug's Therapeutic Target	5.60e-01	5.60e-01	486	90	2	23467	Malignant cells	FGFR3,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	6.90e-02	6.90e-02	119	186	3	23467	B cells	MYC,CXCR4,VIM
Regulation by the Disease Microenvironment	6.40e-02	6.40e-02	52	186	2	23467	CD4+ T cells	SOCS3,VIM
Regulation by the Disease Microenvironment	2.00e-01	2.00e-01	103	186	2	23467	CD8+ T cells	VIM,MALAT1
Regulation by the Disease Microenvironment	1.00e+00	1.00e+00	59	186	0	23467	cDCs	NA
Regulation by the Disease Microenvironment	1.00e+00	1.00e+00	40	186	0	23467	Erythrocytes	NA
Regulation by the Disease Microenvironment	1.40e-01	1.40e-01	82	186	2	23467	Mono_Macro	IL1B,VIM
Regulation by the Disease Microenvironment	2.50e-01	2.50e-01	122	186	2	23467	NK cells	CXCR4,VIM
Regulation by the Disease Microenvironment	1.00e+00	1.00e+00	1	186	0	23467	pDCs	NA
Regulation by the Disease Microenvironment	1.00e+00	1.00e+00	13	186	0	23467	Progenitors	NA

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	2.20e-07	1.10e-06	511	781	41	23467	Malignant cells	ANXA2,CCND2,CDKN1A,CFLAR,FBXW7,GSTP1,IDH2,IFI27,ISG15,MAP1LC3B,MYC,RHOA,RPS6,S100A4,HSPA5,CCND1,HSPD1,CXCR4,DKK1,HSP90B1,GAPDH,HAX1,HMGB2,HSPA8,NFKBIA,LDHA,NSD2,NUCKS1,PDCD4,POMP,SRSF2,UCP2,ENO1,CALR,FGFR3,INSIG1,MDK,RCN1,PMVK,QPRT,APP
Drug Inactivation by Structure Modification	4.50e-01	6.60e-01	511	27	1	23467	Malignant cells	GSTP1
Irregularity in Drug Uptake and Drug Efflux	5.60e-01	6.60e-01	511	37	1	23467	Malignant cells	SLC3A2
Aberration of the Drug's Therapeutic Target	5.90e-01	6.60e-01	511	90	2	23467	Malignant cells	IDH2,FGFR3
Epigenetic Alteration of DNA, RNA or Protein	6.60e-01	6.60e-01	511	455	9	23467	Malignant cells	FBXW7,IDH2,PMAIP1,CXCR4,GAPDH,PDCD4,CYTOR,MALAT1,PPP1R15A

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	31	186	0	23467	B cells	NA
Regulation by the Disease Microenvironment	1.00e+00	1.00e+00	81	186	0	23467	CD4+ T cells	NA
Regulation by the Disease Microenvironment	4.90e-01	4.90e-01	85	186	1	23467	CD8+ T cells	CXCR4
Regulation by the Disease Microenvironment	1.00e+00	1.00e+00	8	186	0	23467	cDCs	NA
Regulation by the Disease Microenvironment	1.00e+00	1.00e+00	29	186	0	23467	Erythrocytes	NA
Regulation by the Disease Microenvironment	4.80e-01	4.80e-01	82	186	1	23467	Mono_Macro	IL1B
Regulation by the Disease Microenvironment	5.10e-01	5.10e-01	89	186	1	23467	NK cells	CXCR4
Regulation by the Disease Microenvironment	1.00e+00	1.00e+00	17	186	0	23467	Progenitors	NA

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__M01029	4.91	0.132	MITF; TFE3; TFEB; TFEC (directAnnotation).	B cells
	cisbp__M01738	4.6	0.126	BHLHE40 (inferredBy_Orthology).	B cells
	transfac_pro__M05916	4.39	0.122	ZNF407 (directAnnotation).	B cells
	tfdimers__MD00029	4.39	0.122	IKZF2; NKX3-2 (directAnnotation).	B cells
	tfdimers__MD00527	4.28	0.119	IRF1; IRF2; IRF3; IRF4; IRF5; IRF6; IRF7; IRF8; ZEB1 (directAnnotation).	B cells
	taipale_tf_pairs__FOXJ2_PITX1_NTAATCCNNWMAACA_CAP_repr	4.13	0.116	FOXJ2; PITX1 (directAnnotation).	B cells
	metacluster_155.7	4.07	0.115	KLF8; ZSCAN1; ZSCAN1; ZSCAN4; ZSCAN4; ZSCAN4 (directAnnotation).	B cells
	cisbp__M01497	3.9	0.111	MAX (directAnnotation).	B cells
	transfac_pro__M06751	3.86	0.111	ZNF510 (directAnnotation).	B cells
	tfdimers__MD00217	3.84	0.11	LTF; MZF1 (directAnnotation).	B 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
	taipale_tf_pairs__TEAD4_ETV1_RSCGGAAATRCM_CAP	5.76	0.115	ETV1; TEAD4 (directAnnotation).	B cells
	taipale_tf_pairs__TEAD4_ETV4_RCCGGAAATRCC_CAP	5.54	0.111	ETV4; TEAD4 (directAnnotation).	B cells
	transfac_pro__M05402	5.26	0.106	BCL6B (directAnnotation).	B cells
	taipale_tf_pairs__TEAD4_ERG_RSCGGAAATRCC_CAP	5.05	0.103	ERG; TEAD4 (directAnnotation).	B cells
	taipale_tf_pairs__TEAD4_ERG_RSCGGAAATRCC_CAP_repr	5.02	0.102	ERG; TEAD4 (directAnnotation).	B cells
	homer__GGCVGTTR_MYB	4.64	0.0961	MYB (inferredBy_Orthology).	B cells
	kznf__CTCF_Rhee2011.3_ChIP-exo	4.63	0.0959	CTCF (directAnnotation).	B cells
	metacluster_23.5	4.61	0.0956	WT1 (directAnnotation).	B cells
	taipale__ELK1_full_NACTTCCGSCGGAARMN_repr	4.61	0.0955	ELK1 (directAnnotation).	B cells
	metacluster_5.1	4.58	0.0949	HIVEP1; HIVEP1; NFAT5; NFKB1; NFKB1; NFKB1; NFKB1; NFKB1; NFKB1; NFKB1; NFKB1; NFKB1; NFKB2; NFKB2; NFKB2; NFKB2; NFKB2; REL; REL; REL; RELA; RELA; RELA; RELA; RELA; RELA; RELA; RELA; RELA; RELA; RELA; RELA; RELA; RELA; RELA; RELA; RELA; RELA; RELA; RELA; RELA; RELA; RELB; RELB (directAnnotation). NFAT5; NFKB1; NFKB1; NFKB1; NFKB1; NFKB1; NFKB2; NFKB2; NFKB2; REL; REL; REL; REL; RELA; RELA; RELA; RELA; RELA; RELB; RELB; RELB (inferredBy_Orthology).	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
	kznf__ZSCAN16_Schmitges2016_ChIP-seq	5.69	0.289	ZSCAN16 (directAnnotation).	B cells
	metacluster_71.5	5.49	0.28	HIF1A (directAnnotation).	B cells
	cisbp__M01802	5.39	0.275	XBP1 (inferredBy_Orthology).	B cells
	tfdimers__MD00380	5.34	0.273	ARID3A; ING4 (directAnnotation).	B cells
	transfac_pro__M05304	5.16	0.264	ZBTB5 (directAnnotation).	B cells
	taipale_tf_pairs__ETV2_DRGX_RSCGGAWRYATTA_CAP_repr	5.1	0.262	DRGX; ETV2 (directAnnotation).	B cells
	cisbp__M01815	4.87	0.251	CEBPE (inferredBy_Orthology).	B cells
	taipale_tf_pairs__MEIS1_SOX2_TGACAKNNNAACAATGN_CAP_repr	4.2	0.22	MEIS1; SOX2 (directAnnotation).	B cells
	taipale_tf_pairs__TEAD4_CLOCK_NCACGTGNNNNNNCATWCC_CAP_repr	4.18	0.22	CLOCK; TEAD4 (directAnnotation).	B cells
	transfac_pro__M07078	4.18	0.219	BHLHE40 (inferredBy_Orthology).	B cells

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

motif	motif	NES	AUC	TF_highConf	Cell_type
	swissregulon__hs__HSF2	5.98	0.173	HSF2 (directAnnotation).	B cells
	taipale_tf_pairs__TEAD4_ERG_RSCGGAAATRCC_CAP_repr	5.95	0.172	ERG; TEAD4 (directAnnotation).	B cells
	taipale_tf_pairs__TEAD4_ERG_RSCGGAAATRCC_CAP	5.72	0.166	ERG; TEAD4 (directAnnotation).	B cells
	hocomoco__TYY2_HUMAN.H11MO.0.D	5.38	0.158	YY2 (directAnnotation).	B cells
	taipale_tf_pairs__TEAD4_ETV1_RSCGGAAATRCM_CAP	5.16	0.152	ETV1; TEAD4 (directAnnotation).	B cells
	tfdimers__MD00349	5.07	0.15	GABPA; YY2 (directAnnotation).	B cells
	metacluster_21.4	4.99	0.148	HSF1; HSF1; HSF2 (directAnnotation). HSF1; HSF2; HSF4; HSF5; HSFX1; HSFX2; HSFX3; HSFX4; HSFY1; HSFY2 (inferredBy_Orthology).	B cells
	transfac_pro__M05560	4.98	0.147	AEBP2 (directAnnotation).	B cells
	transfac_pro__M06939	4.83	0.144	ZBTB11 (directAnnotation).	B cells
	transfac_pro__M02279	4.77	0.142	CREB1 (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
FOS	tfdimers__MD00090	down	CD4+ T cells	post
SCAND1	metacluster_130.3	down	CD8+ T cells	post
JUN	metacluster_111.4	down	CD8+ T cells	post
JUND	metacluster_111.4	down	CD8+ T cells	post
FOS	metacluster_111.4	down	CD8+ T cells	post
FOS	metacluster_137.2	down	CD8+ T cells	post
JUN	metacluster_137.2	down	CD8+ T cells	post
JUND	metacluster_137.2	down	CD8+ T cells	post
JUN	metacluster_180.3	down	CD8+ T cells	post
JUND	metacluster_180.3	down	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."