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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: GSE111014

Dataset summary for GSE111014

Datast information	Dataset	GSE111014
	PMID	31996669
	Raw data ID/link	PRJNA435591
	Organism	Homo sapiens
	Source	patients
	Tissue	Peripheral blood mononuclear cells
	Cancer type level1	Chronic lymphocytic leukemia
	Cancer type level2	Chronic lymphocytic leukemia (CLL)
	Regimen	ibrutinib
	Drug type	Targeted therapy
	Sample size	pre (resistant 1, sensitive 3); post (resistant 1, sensitive 3)
	Cell number	24790
	Extract protocol	10x genomics
	Data processing	CellRanger 2.0.0
	Public date	Public on Feb 22, 2019
	Description	This dataset has 4 patients with both pre -and post-treatment samples.

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Drug summary for GSE111014

Drug name	DrugBank ID	Drug type	Targets name	Targets uniprot ID
"Ibrutinib"	DB09053	small molecule	BTK	Q06187

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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
RPL41	ENSG00000229117	2.42177	2.86e-26	4.83e-22	1	0.62	NK cells	pre
RPL39	ENSG00000198918	2.16777	1.55e-26	2.63e-22	1	0.446	NK cells	pre
EEF1A1	ENSG00000156508	1.97226	2.25e-25	3.81e-21	1	0.587	NK cells	pre
IGKC	ENSG00000211592	1.59733	3.02e-18	5.11e-14	0.759	0.116	NK cells	pre
H3F3A	NA	1.2923	6.90e-19	1.17e-14	0.685	0.066	NK cells	pre
CD74	ENSG00000019582	1.04428	1.73e-07	2.93e-03	0.907	0.636	NK cells	pre
HLA-DRA	ENSG00000277263	0.846635	6.96e-07	1.18e-02	0.556	0.207	NK cells	pre
TMSB4X	ENSG00000205542	0.587665	6.54e-10	1.11e-05	1	0.992	NK cells	pre
RPL7	ENSG00000147604	0.561495	1.00e-08	1.70e-04	1	0.975	NK cells	pre
B2M	ENSG00000273686	0.476693	9.20e-09	1.56e-04	1	1	NK cells	pre
CALM3	ENSG00000160014	-0.510929	2.02e-06	3.42e-02	0.056	0.413	NK cells	pre
FLNA	ENSG00000196924	-0.560712	1.77e-06	2.99e-02	0.093	0.463	NK cells	pre
RPS12	ENSG00000112306	-0.607632	7.12e-07	1.21e-02	1	0.983	NK cells	pre
FUS	ENSG00000089280	-0.616003	2.18e-07	3.69e-03	0.278	0.719	NK cells	pre
TPST2	ENSG00000128294	-0.616538	1.72e-08	2.92e-04	0.148	0.603	NK cells	pre
AKNA	ENSG00000106948	-0.665294	6.73e-09	1.14e-04	0.037	0.496	NK cells	pre
ZFP36L2	ENSG00000152518	-0.698521	2.61e-09	4.42e-05	0.148	0.669	NK cells	pre
RP5-1171I10.5	NA	-0.749313	2.53e-09	4.29e-05	0.093	0.587	NK cells	pre
MT-ND4	ENSG00000198886	-0.762332	5.72e-10	9.68e-06	0.981	1	NK cells	pre
MT-CO1	ENSG00000198804	-0.800639	6.02e-11	1.02e-06	1	1	NK cells	pre
MALAT1	ENSG00000251562	-0.836709	1.00e-12	1.70e-08	1	1	NK cells	pre
NEAT1	ENSG00000245532	-0.849487	7.09e-09	1.20e-04	0.296	0.769	NK cells	pre
MT-ND2	ENSG00000198763	-0.912599	2.39e-08	4.05e-04	0.722	0.926	NK cells	pre
MT-ND1	ENSG00000198888	-0.931181	1.76e-08	2.98e-04	0.556	0.893	NK cells	pre
RPS26	ENSG00000197728	-1.01593	4.06e-10	6.87e-06	0.481	0.851	NK cells	pre
RPS4Y1	ENSG00000129824	-1.06982	1.33e-14	2.26e-10	0	0.661	NK cells	pre
JUN	ENSG00000177606	-1.07085	1.97e-08	3.34e-04	0.426	0.802	NK cells	pre
RPL39	ENSG00000198918	2.51767	3.06e-29	5.18e-25	1	0.493	Mono/Macro	pre
RPL41	ENSG00000229117	2.4881	5.33e-30	9.01e-26	1	0.458	Mono/Macro	pre
EEF1A1	ENSG00000156508	2.33573	2.01e-28	3.40e-24	1	0.427	Mono/Macro	pre
H3F3A	NA	2.08849	0.00e+00	0.00e+00	1	0.093	Mono/Macro	pre
RPL36A	ENSG00000241343	1.04365	9.11e-15	1.54e-10	0.895	0.426	Mono/Macro	pre
IGKC	ENSG00000211592	1.00183	1.05e-17	1.78e-13	0.474	0.075	Mono/Macro	pre
FOS	ENSG00000170345	0.93918	2.33e-08	3.94e-04	0.921	0.795	Mono/Macro	pre
HLA-DRB5	ENSG00000198502	0.797935	3.48e-21	5.88e-17	0.658	0.118	Mono/Macro	pre
ZFP36	ENSG00000128016	0.716332	5.45e-09	9.22e-05	0.737	0.362	Mono/Macro	pre
XIST	ENSG00000229807	0.713741	0.00e+00	0.00e+00	0.395	0.011	Mono/Macro	pre
HLA-DQB1	ENSG00000206237	0.662316	3.79e-09	6.41e-05	0.737	0.327	Mono/Macro	pre
SH3BGRL3	ENSG00000142669	0.616166	1.50e-08	2.53e-04	1	0.977	Mono/Macro	pre
RPL21	ENSG00000122026	0.568299	8.39e-09	1.42e-04	1	0.987	Mono/Macro	pre
HMGN2	ENSG00000198830	0.548044	9.43e-16	1.60e-11	0.5	0.094	Mono/Macro	pre
RPS28	ENSG00000233927	0.52769	1.10e-06	1.87e-02	1	0.915	Mono/Macro	pre
GABARAP	ENSG00000170296	0.443475	9.84e-10	1.66e-05	0.447	0.117	Mono/Macro	pre
TNNT1	ENSG00000105048	0.438525	1.53e-16	2.59e-12	0.421	0.063	Mono/Macro	pre
AC090498.1	NA	0.436901	2.06e-33	3.48e-29	0.289	0.011	Mono/Macro	pre
TBCA	ENSG00000171530	0.431567	1.67e-06	2.82e-02	0.658	0.302	Mono/Macro	pre
EGR1	ENSG00000120738	0.427545	1.52e-11	2.58e-07	0.368	0.07	Mono/Macro	pre
ELF1	ENSG00000120690	0.423705	8.03e-07	1.36e-02	0.5	0.186	Mono/Macro	pre
M6PR	ENSG00000003056	0.318611	4.71e-09	7.97e-05	0.342	0.074	Mono/Macro	pre
BZW1	ENSG00000082153	0.304099	1.26e-06	2.14e-02	0.316	0.085	Mono/Macro	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
GNLY	ENSG00000115523	1.79893	0.00e+00	0.00e+00	0.969	0.695	NK cells	post
FCER1G	ENSG00000158869	1.54344	0.00e+00	0.00e+00	0.687	0.051	NK cells	post
GZMB	ENSG00000100453	1.41152	0.00e+00	0.00e+00	0.823	0.358	NK cells	post
GZMA	ENSG00000145649	1.37262	0.00e+00	0.00e+00	0.862	0.345	NK cells	post
CTSW	ENSG00000172543	1.34885	0.00e+00	0.00e+00	0.825	0.286	NK cells	post
NKG7	ENSG00000105374	1.22469	0.00e+00	0.00e+00	0.975	0.769	NK cells	post
SRGN	ENSG00000122862	1.16635	0.00e+00	0.00e+00	0.724	0.182	NK cells	post
B2M	ENSG00000273686	1.16089	0.00e+00	0.00e+00	1	1	NK cells	post
KLRB1	ENSG00000111796	1.14881	0.00e+00	0.00e+00	0.651	0.136	NK cells	post
CST7	ENSG00000077984	1.10465	0.00e+00	0.00e+00	0.868	0.367	NK cells	post
PRF1	ENSG00000180644	1.09767	0.00e+00	0.00e+00	0.78	0.293	NK cells	post
TYROBP	ENSG00000011600	1.07995	0.00e+00	0.00e+00	0.696	0.163	NK cells	post
ACTB	ENSG00000075624	1.02229	0.00e+00	0.00e+00	1	0.999	NK cells	post
PFN1	ENSG00000108518	1.01936	0.00e+00	0.00e+00	0.997	0.993	NK cells	post
CD7	ENSG00000173762	1.01585	0.00e+00	0.00e+00	0.673	0.139	NK cells	post
TMSB4X	ENSG00000205542	0.956757	0.00e+00	0.00e+00	1	0.999	NK cells	post
PLAC8	ENSG00000145287	0.947662	0.00e+00	0.00e+00	0.538	0.058	NK cells	post
IFITM2	ENSG00000185201	0.935891	0.00e+00	0.00e+00	0.707	0.249	NK cells	post
MYL12A	ENSG00000101608	0.906715	1.40e-45	1.31e-41	0.831	0.472	NK cells	post
CLIC1	ENSG00000226651	0.820055	0.00e+00	1.40e-45	0.685	0.224	NK cells	post
CCL5	ENSG00000274233	0.799014	1.99e-27	3.37e-23	0.834	0.673	NK cells	post
FGFBP2	ENSG00000137441	0.796762	5.61e-36	9.49e-32	0.527	0.166	NK cells	post
HLA-A	ENSG00000227715	0.782554	0.00e+00	0.00e+00	1	0.999	NK cells	post
FCGR3A	ENSG00000203747	0.7643	0.00e+00	0.00e+00	0.482	0.072	NK cells	post
HOPX	ENSG00000171476	0.7452	1.40e-44	2.45e-40	0.513	0.127	NK cells	post
ARPC2	ENSG00000163466	0.732174	1.85e-39	3.13e-35	0.679	0.255	NK cells	post
SPON2	ENSG00000159674	0.731263	1.31e-40	2.22e-36	0.423	0.097	NK cells	post
PSMB9	ENSG00000239836	0.723146	0.00e+00	4.41e-43	0.679	0.212	NK cells	post
CD53	ENSG00000143119	0.71538	0.00e+00	1.82e-44	0.504	0.11	NK cells	post
CFL1	ENSG00000172757	0.713689	1.40e-45	2.88e-41	0.932	0.941	NK cells	post
KLRF1	ENSG00000150045	0.711846	0.00e+00	0.00e+00	0.465	0.052	NK cells	post
KLRD1	ENSG00000134539	0.692187	5.52e-40	9.34e-36	0.631	0.21	NK cells	post
HLA-C	ENSG00000206435	0.685235	0.00e+00	0.00e+00	1	0.999	NK cells	post
RAC2	ENSG00000128340	0.681179	1.52e-38	2.58e-34	0.572	0.182	NK cells	post
TRDC	ENSG00000211829	0.646047	0.00e+00	0.00e+00	0.425	0.062	NK cells	post
ALOX5AP	ENSG00000132965	0.645395	4.31e-42	7.30e-38	0.366	0.057	NK cells	post
CMC1	ENSG00000187118	0.642544	1.36e-27	2.29e-23	0.499	0.178	NK cells	post
CALM1	ENSG00000198668	0.640768	2.38e-32	4.03e-28	0.668	0.282	NK cells	post
CYBA	ENSG00000051523	0.638003	1.92e-33	3.25e-29	0.946	0.969	NK cells	post
CD247	ENSG00000198821	0.609856	3.60e-43	6.09e-39	0.493	0.11	NK cells	post
ID2	ENSG00000115738	0.609817	3.03e-28	5.12e-24	0.577	0.229	NK cells	post
CLIC3	ENSG00000169583	0.602885	1.01e-39	1.70e-35	0.411	0.091	NK cells	post
PSME2	ENSG00000284889	0.602009	9.00e-32	1.52e-27	0.575	0.206	NK cells	post
CCL4	ENSG00000277943	0.591196	1.94e-32	3.27e-28	0.518	0.157	NK cells	post
RARRES3	NA	0.588061	3.23e-29	5.46e-25	0.566	0.213	NK cells	post
LY6E	ENSG00000278032	0.586492	2.29e-27	3.87e-23	0.521	0.196	NK cells	post
CD63	ENSG00000135404	0.578502	1.34e-34	2.27e-30	0.493	0.137	NK cells	post
HCST	ENSG00000126264	0.575842	1.96e-23	3.32e-19	0.758	0.434	NK cells	post
ITM2B	ENSG00000136156	0.550065	6.87e-31	1.16e-26	0.476	0.144	NK cells	post
UBB	ENSG00000170315	0.548622	1.01e-25	1.71e-21	0.851	0.795	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	3.20e-03	1.60e-02	222	781	16	23467	Malignant cells	ANXA2,GSTP1,JUN,S100A4,BTG1,CXCR4,DUSP1,FTL,FUS,GAPDH,GRB2,ITGB1,HNRNPA1,TPT1,UCP2,CALR
Epigenetic Alteration of DNA, RNA or Protein	1.40e-01	3.50e-01	222	455	7	23467	Malignant cells	EIF4G2,CXCR4,GAPDH,MALAT1,PPP1R15A,MT-CO2,GABPB1-AS1
Drug Inactivation by Structure Modification	2.30e-01	3.80e-01	222	27	1	23467	Malignant cells	GSTP1
Aberration of the Drug's Therapeutic Target	1.00e+00	1.00e+00	222	90	0	23467	Malignant cells
Irregularity in Drug Uptake and Drug Efflux	1.00e+00	1.00e+00	222	37	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	1.10e-01	1.10e-01	148	186	3	23467	CD4+ T cells	GATA3,VIM,MALAT1
Regulation by the Disease Microenvironment	1.10e-02	1.10e-02	168	186	5	23467	CD8+ T cells	TGFB1,ZEB2,FYN,HNRNPA2B1,MALAT1
Regulation by the Disease Microenvironment	3.00e-01	3.00e-01	44	186	1	23467	Mono_Macro	MALAT1
Regulation by the Disease Microenvironment	1.90e-01	1.90e-01	27	186	1	23467	NK cells	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	2.60e-02	1.30e-01	127	781	9	23467	Malignant cells	JUN,S100A4,BTG1,CXCR4,FTL,GAPDH,TCF4,HNRNPA1,TPT1
Epigenetic Alteration of DNA, RNA or Protein	2.30e-01	5.80e-01	127	455	4	23467	Malignant cells	CXCR4,GAPDH,MALAT1,GABPB1-AS1
Aberration of the Drug's Therapeutic Target	1.00e+00	1.00e+00	127	90	0	23467	Malignant cells
Drug Inactivation by Structure Modification	1.00e+00	1.00e+00	127	27	0	23467	Malignant cells
Irregularity in Drug Uptake and Drug Efflux	1.00e+00	1.00e+00	127	37	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	57	186	0	23467	CD4+ T cells	NA
Regulation by the Disease Microenvironment	2.10e-01	2.10e-01	197	186	3	23467	CD8+ T cells	ZEB2,FYN,MALAT1
Regulation by the Disease Microenvironment	1.00e+00	1.00e+00	19	186	0	23467	Mono_Macro	NA
Regulation by the Disease Microenvironment	6.00e-01	6.00e-01	256	186	2	23467	NK cells	HNRNPA2B1,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
	tfdimers__MD00440	6.61	0.121	FOXI1; IRF1 (directAnnotation).	CD4+ T cells
	tfdimers__MD00029	5.93	0.11	IKZF2; NKX3-2 (directAnnotation).	CD4+ T cells
	transfac_pro__M05798	5.79	0.108	ZNF517 (directAnnotation).	CD4+ T cells
	taipale_tf_pairs__ETV2_SPDEF_NSCGGACGGAWATCCGSNT_CAP	5.36	0.101	ETV2; SPDEF (directAnnotation).	CD4+ T cells
	transfac_pro__M05815	5.08	0.0969	ZNF613 (directAnnotation).	CD4+ T cells
	jaspar__MA1998.1	4.69	0.0909	PRDM14 (inferredBy_Orthology).	CD4+ T cells
	transfac_pro__M05907	4.55	0.0886	ZNF416 (directAnnotation).	CD4+ T cells
	taipale_cyt_meth__JUND_NRTGACGCATN_eDBD_repr	4.55	0.0886	JUND (directAnnotation).	CD4+ T cells
	taipale_cyt_meth__ELF3_NTGTGCGGATGCN_FL_repr	4.24	0.0838	ELF3 (directAnnotation).	CD4+ T cells
	transfac_pro__M01069	4.21	0.0834	GZF1 (directAnnotation).	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
	transfac_pro__M05352	4.14	0.0831	ZNF692 (inferredBy_Orthology).	CD4+ T cells
	transfac_pro__M05472	4.11	0.0827	ZBTB41 (directAnnotation).	CD4+ T cells
	transfac_pro__M06257	4.05	0.0819	ZNF616 (directAnnotation).	CD4+ T cells
	taipale_cyt_meth__NR4A1_NAAAGGTCAN_eDBD_1	3.98	0.081	NR4A1 (directAnnotation).	CD4+ T cells
	transfac_pro__M12355	3.86	0.0792	ZNF549 (directAnnotation).	CD4+ T cells
	metacluster_72.1	3.65	0.0763	ZNF423; ZNF423 (directAnnotation).	CD4+ T cells
	metacluster_157.2	3.56	0.0751	ATF3; ATF3; ATF3; BACH1; BACH1; BACH1; BACH2; BACH2; BACH2; BACH2; BATF; BATF; BCL11A; FOS; FOS; FOS; FOS; FOS; FOS; FOSB; FOSL1; FOSL1; FOSL1; FOSL1; FOSL1; FOSL1; FOSL2; FOSL2; FOSL2; JDP2; JDP2; JDP2; JDP2; JDP2; JDP2; JDP2; JUN; JUN; JUN; JUN; JUN; JUNB; JUNB; JUNB; JUNB; JUNB; JUNB; JUND; JUND; JUND; JUND; JUND; JUND; JUND; JUND; JUND; MAF; MAFB; MAFF; MAFG; MAFK; NFE2; NFE2; NFE2; NFE2; NFE2; NFE2; NFE2L1; NFE2L1; NFE2L2; NFE2L3; ZNF3; ZSCAN5C (directAnnotation). FOSL1; JUN; JUN; JUN; JUNB; JUNB; JUND (inferredBy_Orthology).	CD4+ T cells
	taipale_tf_pairs__FOXJ2_ELF1_RMAGAAAACCGAANN_CAP_repr	3.51	0.0744	ELF1; FOXJ2 (directAnnotation).	CD4+ T cells
	taipale_tf_pairs__FOXO1_ELF1_NNGAAAACCGAANM_CAP	3.5	0.0742	ELF1; FOXO1 (directAnnotation).	CD4+ T cells
	metacluster_167.7	3.43	0.0733	IRF8 (inferredBy_Orthology).	CD4+ T 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
	metacluster_79.1	6.55	0.125	ZNF713; ZNF713; ZNF713 (directAnnotation).	CD4+ T cells
	taipale_tf_pairs__ERF_HOXA3_RSCGGAWNNNNNNNYMATTA_CAP_repr	6.04	0.117	ERF; HOXA3 (directAnnotation).	CD4+ T cells
	hocomoco__TYY2_HUMAN.H11MO.0.D	5.66	0.111	YY2 (directAnnotation).	CD4+ T cells
	transfac_pro__M04844	4.96	0.0988	MAX (directAnnotation).	CD4+ T cells
	transfac_pro__M06763	4.86	0.0972	ZNF225 (directAnnotation).	CD4+ T cells
	hdpi__FLI1	4.84	0.0969	FLI1 (directAnnotation).	CD4+ T cells
	transfac_pro__M07392	4.79	0.0961	PITX3 (directAnnotation).	CD4+ T cells
	transfac_pro__M05711	4.57	0.0923	ZNF37A (directAnnotation).	CD4+ T cells
	transfac_pro__M05894	4.51	0.0914	ZNF565 (directAnnotation).	CD4+ T cells
	taipale_tf_pairs__ETV2_SPDEF_NSCGGACGGAWATCCGSNT_CAP	4.43	0.0899	ETV2; SPDEF (directAnnotation).	CD4+ T 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
	metacluster_63.4	7.12	0.264	ZNF672 (directAnnotation).	CD4+ T cells
	tfdimers__MD00134	6.96	0.258	DBP; GTF2IRD1 (directAnnotation).	CD4+ T cells
	nitta__Ets98B_TTCCCC20NTA_KH_TKGCGGATGCN_m1_c3	6.64	0.247	SPDEF (inferredBy_Orthology).	CD4+ T cells
	transfac_pro__M06702	5.95	0.224	ZNF226 (directAnnotation).	CD4+ T cells
	transfac_pro__M06063	5.72	0.216	ZNF99 (directAnnotation).	CD4+ T cells
	dbtfbs__ZNF660_HEK293_ENCSR283DOU_merged_N1	5.7	0.215	ZNF660 (directAnnotation).	CD4+ T cells
	taipale_tf_pairs__GCM1_CEBPB_MTRSGGGNNNNNNTTRCGYAAN_CAP	5.66	0.214	CEBPB; GCM1 (directAnnotation).	CD4+ T cells
	transfac_pro__M06568	5.52	0.209	ZNF501 (directAnnotation).	CD4+ T cells
	nitta__Ets98B_TTCCCC20NTA_KH_TAMCGGATGCN_m1_c3	5.38	0.204	SPDEF (inferredBy_Orthology).	CD4+ T cells
	taipale_tf_pairs__ETV5_FOXI1_TGTTGNCGGAWRN_CAP	5.25	0.2	ETV5; FOXI1 (directAnnotation).	CD4+ T 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
JUN	tfdimers__MD00475	down	CD8+ T cells	post
IKZF1	tfdimers__MD00265	down	CD8+ T cells	post
FOS	metacluster_157.2	down	CD4+ T cells	pre
JUN	metacluster_157.2	down	CD4+ T cells	pre
FOS	jaspar__MA1951.1	down	CD4+ T cells	pre
GATA3	tfdimers__MD00187	down	CD4+ T cells	pre
IRF1	tfdimers__MD00527	down	CD8+ T cells	pre
JUN	cisbp__M01816	down	Malignant cells	pre
ELF1	taipale_tf_pairs__FOXJ3_ELF1_NNARAAAACCGAAWMN_CAP	up	Mono/Macro	pre
ELF1	taipale_tf_pairs__FOXO1_ELF1_NNGAAAACCGAANM_CAP	up	Mono/Macro	pre

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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."