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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: GSE199333

Dataset summary for GSE199333

Datast information	Dataset	GSE199333
	PMID	NA
	Raw data ID/link	NA
	Organism	Homo sapiens
	Source	patients
	Tissue	Bone marrow aspirate
	Cancer type level1	Acute myeloid leukemia
	Cancer type level2	Primary FLT3-ITD-mutated acute myeloid leukemia (AML)
	Regimen	gilteritinib
	Drug type	Targeted therapy
	Sample size	pre (resistant 3, sensitive 4); post (resistant 3, sensitive 4)
	Cell number	105004
	Extract protocol	10x genomics
	Data processing	CellRanger 3.1.0
	Public date	Public on Jul 07, 2022
	Description	This dataset has 7 patients with both pre -and post-treatment samples.

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Drug summary for GSE199333

Drug name	DrugBank ID	Drug type	Targets name	Targets uniprot ID
"Gilteritinib"	DB12141	small molecule	FLT3; AXL; ALK	P36888; P30530; Q9UM73

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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
CCL4	ENSG00000277943	2.35498	6.07e-39	1.29e-34	0.883	0.642	NK cells	pre
CXCR4	ENSG00000121966	2.02652	0.00e+00	0.00e+00	0.875	0.143	NK cells	pre
S100B	ENSG00000160307	1.99869	8.89e-34	1.89e-29	0.621	0.204	NK cells	pre
HBB	ENSG00000244734	1.59186	0.00e+00	0.00e+00	0.969	0.808	NK cells	pre
IGKC	ENSG00000211592	1.5595	0.00e+00	1.12e-44	0.619	0.064	NK cells	pre
CCL4L2	ENSG00000282604	1.5556	1.59e-16	3.37e-12	0.365	0.102	NK cells	pre
ZFP36	ENSG00000128016	1.47348	0.00e+00	0.00e+00	0.787	0.204	NK cells	pre
DUSP2	ENSG00000158050	1.4045	8.23e-43	1.75e-38	0.72	0.234	NK cells	pre
MYOM2	ENSG00000274137	1.29501	4.57e-43	9.69e-39	0.503	0.008	NK cells	pre
CD3D	ENSG00000167286	1.26881	8.99e-32	1.91e-27	0.66	0.2	NK cells	pre
CD3G	ENSG00000160654	1.26643	7.79e-34	1.65e-29	0.601	0.136	NK cells	pre
HLA-DRB1	ENSG00000228080	1.20348	6.25e-31	1.33e-26	0.609	0.208	NK cells	pre
CD52	ENSG00000169442	1.18758	3.22e-44	6.70e-40	0.963	0.581	NK cells	pre
JUNB	ENSG00000171223	1.17885	1.06e-34	2.25e-30	0.855	0.525	NK cells	pre
HBA2	ENSG00000188536	1.15708	0.00e+00	0.00e+00	0.889	0.664	NK cells	pre
TNFAIP3	ENSG00000118503	1.11106	1.17e-39	2.48e-35	0.673	0.177	NK cells	pre
CD3E	ENSG00000198851	1.10281	2.27e-32	4.82e-28	0.725	0.298	NK cells	pre
TRGC1	ENSG00000211689	1.06833	5.52e-18	1.17e-13	0.567	0.302	NK cells	pre
TSC22D3	ENSG00000157514	1.02046	2.76e-26	5.85e-22	0.816	0.517	NK cells	pre
NR4A2	ENSG00000153234	0.97429	3.80e-28	8.08e-24	0.549	0.151	NK cells	pre
NFKBIA	ENSG00000100906	0.948972	6.70e-29	1.42e-24	0.739	0.336	NK cells	pre
S100A4	ENSG00000196154	0.935939	2.60e-33	5.53e-29	0.997	0.974	NK cells	pre
TRGC2	ENSG00000227191	0.913912	4.60e-13	9.76e-09	0.477	0.23	NK cells	pre
IL32	ENSG00000008517	0.896214	3.29e-26	6.98e-22	0.907	0.611	NK cells	pre
PTGDS	ENSG00000107317	0.839017	7.87e-12	1.67e-07	0.344	0.117	NK cells	pre
CD69	ENSG00000110848	0.811399	7.89e-20	1.68e-15	0.616	0.287	NK cells	pre
DDIT4	ENSG00000168209	0.808043	1.18e-25	2.51e-21	0.607	0.219	NK cells	pre
PPP2R5C	ENSG00000078304	0.799082	2.70e-24	5.73e-20	0.839	0.547	NK cells	pre
AREG	ENSG00000109321	0.798904	1.60e-16	3.39e-12	0.285	0.038	NK cells	pre
KLRG1	ENSG00000139187	0.757446	1.02e-23	2.16e-19	0.692	0.302	NK cells	pre
TRDC	ENSG00000211829	0.747399	8.72e-12	1.85e-07	0.748	0.611	NK cells	pre
KLRC1	ENSG00000134545	0.740581	1.45e-14	3.07e-10	0.601	0.332	NK cells	pre
CEMIP2	ENSG00000135048	0.716818	1.24e-17	2.63e-13	0.52	0.196	NK cells	pre
TENT5C	ENSG00000183508	0.694644	2.08e-22	4.41e-18	0.43	0.087	NK cells	pre
HBA1	ENSG00000206172	0.678401	6.69e-28	1.42e-23	0.769	0.54	NK cells	pre
PIK3R1	ENSG00000145675	0.67081	5.62e-16	1.19e-11	0.678	0.4	NK cells	pre
SPOCK2	ENSG00000107742	0.632374	1.95e-16	4.13e-12	0.507	0.196	NK cells	pre
DUSP1	ENSG00000120129	0.627666	5.31e-12	1.13e-07	0.588	0.332	NK cells	pre
PRDX2	ENSG00000167815	0.596697	2.50e-16	5.30e-12	0.518	0.215	NK cells	pre
S100A6	ENSG00000197956	0.569517	2.16e-16	4.58e-12	0.984	0.906	NK cells	pre
ATG2A	ENSG00000110046	0.55848	2.22e-13	4.71e-09	0.423	0.158	NK cells	pre
BTG2	ENSG00000159388	0.545337	2.46e-14	5.23e-10	0.497	0.215	NK cells	pre
TECR	ENSG00000099797	0.521869	9.05e-07	1.92e-02	0.503	0.347	NK cells	pre
NDUFB8	ENSG00000166136	0.510416	1.05e-12	2.22e-08	0.575	0.313	NK cells	pre
BTG1	ENSG00000133639	0.507774	2.71e-15	5.75e-11	0.982	0.951	NK cells	pre
BHLHE40	ENSG00000134107	0.505729	3.23e-12	6.86e-08	0.472	0.215	NK cells	pre
SERTAD1	ENSG00000197019	0.502421	3.61e-15	7.66e-11	0.41	0.128	NK cells	pre
TSPO	ENSG00000100300	0.501655	2.00e-12	4.24e-08	0.749	0.513	NK cells	pre
GNLY	ENSG00000115523	0.499992	3.70e-15	7.86e-11	1	0.894	NK cells	pre
GADD45B	ENSG00000099860	0.49334	6.20e-11	1.32e-06	0.495	0.257	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
NDUFA4	ENSG00000189043	0.303391	0.00e+00	0.00e+00	0.93	0.799	Malignant cells	post
NFIX	ENSG00000008441	0.303331	0.00e+00	0.00e+00	0.298	0.125	Malignant cells	post
GPATCH4	ENSG00000160818	0.303327	0.00e+00	0.00e+00	0.264	0.072	Malignant cells	post
GSTK1	ENSG00000197448	0.302927	0.00e+00	0.00e+00	0.711	0.527	Malignant cells	post
IARS	NA	0.302886	0.00e+00	0.00e+00	0.288	0.089	Malignant cells	post
PSMD13	ENSG00000185627	0.302742	0.00e+00	0.00e+00	0.475	0.264	Malignant cells	post
UROS	ENSG00000188690	0.30263	0.00e+00	0.00e+00	0.327	0.13	Malignant cells	post
CYTOR	ENSG00000222041	0.302575	0.00e+00	0.00e+00	0.423	0.208	Malignant cells	post
TTC1	ENSG00000113312	0.302263	0.00e+00	0.00e+00	0.328	0.12	Malignant cells	post
FNTA	ENSG00000168522	0.302241	0.00e+00	0.00e+00	0.335	0.128	Malignant cells	post
LIMS1	ENSG00000169756	0.302227	0.00e+00	1.34e-41	0.512	0.36	Malignant cells	post
SNRPD2	ENSG00000125743	0.301825	0.00e+00	0.00e+00	0.838	0.671	Malignant cells	post
RPL26	ENSG00000161970	0.301776	0.00e+00	0.00e+00	0.999	0.997	Malignant cells	post
ALG3	ENSG00000214160	0.30172	0.00e+00	0.00e+00	0.296	0.091	Malignant cells	post
COLGALT1	ENSG00000130309	0.301695	0.00e+00	0.00e+00	0.28	0.095	Malignant cells	post
TBXAS1	ENSG00000059377	0.301519	0.00e+00	0.00e+00	0.35	0.152	Malignant cells	post
ZDHHC12	ENSG00000160446	0.300136	0.00e+00	0.00e+00	0.28	0.074	Malignant cells	post
SNRPG	ENSG00000143977	0.299992	0.00e+00	0.00e+00	0.625	0.494	Malignant cells	post
B3GAT3	ENSG00000149541	0.299824	0.00e+00	0.00e+00	0.295	0.088	Malignant cells	post
GNL3	ENSG00000163938	0.29918	0.00e+00	0.00e+00	0.385	0.195	Malignant cells	post
SPCS2	ENSG00000118363	0.299061	0.00e+00	0.00e+00	0.534	0.334	Malignant cells	post
SNHG8	ENSG00000269893	0.298304	0.00e+00	0.00e+00	0.82	0.738	Malignant cells	post
STMP1	ENSG00000243317	0.298103	0.00e+00	0.00e+00	0.629	0.448	Malignant cells	post
IFRD2	ENSG00000214706	0.297917	0.00e+00	0.00e+00	0.273	0.08	Malignant cells	post
PHKB	ENSG00000102893	0.297873	0.00e+00	0.00e+00	0.335	0.143	Malignant cells	post
BCKDK	ENSG00000103507	0.297612	0.00e+00	0.00e+00	0.288	0.078	Malignant cells	post
SEPHS2	ENSG00000179918	0.29756	0.00e+00	0.00e+00	0.351	0.145	Malignant cells	post
ARFRP1	ENSG00000101246	0.297498	0.00e+00	0.00e+00	0.258	0.052	Malignant cells	post
WDR18	ENSG00000065268	0.297195	0.00e+00	0.00e+00	0.279	0.075	Malignant cells	post
DCUN1D5	ENSG00000137692	0.297151	0.00e+00	0.00e+00	0.287	0.084	Malignant cells	post
TMEM59	ENSG00000116209	0.297088	0.00e+00	0.00e+00	0.741	0.578	Malignant cells	post
CALCOCO2	ENSG00000136436	0.297007	0.00e+00	0.00e+00	0.416	0.253	Malignant cells	post
SDHD	ENSG00000204370	0.296936	0.00e+00	0.00e+00	0.419	0.211	Malignant cells	post
ISCA2	ENSG00000165898	0.295847	0.00e+00	0.00e+00	0.291	0.086	Malignant cells	post
COPE	ENSG00000105669	0.295799	0.00e+00	0.00e+00	0.737	0.57	Malignant cells	post
UBE2S	ENSG00000108106	0.295676	0.00e+00	0.00e+00	0.408	0.239	Malignant cells	post
THRAP3	ENSG00000054118	0.295325	0.00e+00	0.00e+00	0.537	0.36	Malignant cells	post
CDC26	ENSG00000176386	0.295118	0.00e+00	0.00e+00	0.295	0.092	Malignant cells	post
POLR2H	ENSG00000163882	0.295069	0.00e+00	0.00e+00	0.353	0.151	Malignant cells	post
EXOSC8	ENSG00000120699	0.294828	0.00e+00	0.00e+00	0.341	0.141	Malignant cells	post
MAN1A1	ENSG00000111885	0.29482	0.00e+00	0.00e+00	0.409	0.245	Malignant cells	post
PSMD8	ENSG00000099341	0.294799	0.00e+00	0.00e+00	0.631	0.446	Malignant cells	post
OST4	ENSG00000228474	0.29405	0.00e+00	0.00e+00	0.9	0.78	Malignant cells	post
SFXN4	ENSG00000183605	0.293981	0.00e+00	0.00e+00	0.293	0.091	Malignant cells	post
HDDC3	ENSG00000184508	0.293931	0.00e+00	0.00e+00	0.25	0.046	Malignant cells	post
TAF15	ENSG00000276833	0.29388	0.00e+00	0.00e+00	0.4	0.193	Malignant cells	post
POP5	ENSG00000167272	0.293876	0.00e+00	0.00e+00	0.336	0.134	Malignant cells	post
DNAJC4	ENSG00000110011	0.293542	0.00e+00	0.00e+00	0.398	0.211	Malignant cells	post
ESYT2	ENSG00000117868	0.293433	0.00e+00	0.00e+00	0.36	0.165	Malignant cells	post
TMEM109	ENSG00000110108	0.293301	0.00e+00	0.00e+00	0.295	0.097	Malignant cells	post

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This dataset only has one patient or is a cell line dataset, the resistant sample is the post-treatment sample and the sensitive sample is the pre-treatment sample. The following are differentially expressed genes (|avg_log2FC|>0.25 & p_val_adj<0.05) between the resistant and sensitive groups for each cell type.

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

Enrichment results for 5 known drug-resistant mechanisms in malignant cells and 1 known mechanism in TME cells.The "Signature" column represents the differentially expressed genes (DEGs) used for enrichment. The "Geneset" column represents the genes included in this mechanism. The "Overlap" column represents the number of genes in the "Geneset" that are enriched in the "Signature". The "Enriched Genes" column represents the genes in the "Geneset" that are enriched in the "Signature". (If the image exists, the user can click on it to enlarge it in a new window.)

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

Mechnism	Pval	FDR	Signature	Geneset	Overlap	Background	Cell type	Enriched Genes
Unusual Activation of Pro-survival Pathway	2.10e-24	1.10e-23	848	781	93	23467	Malignant cells	ANXA2,AREG,BCL11A,BRAF,CCND2,CTNNB1,DNMT1,DUSP6,GSTP1,HIF1A,HMGA1,HOXB3,EIF4G1,JUN,PKM,MEF2D,NFKB1,PARP1,KRAS,RHOA,S100A4,SELENOW,SOCS2,STMN1,TYMS,ZEB2,YWHAZ,SLC25A5,ANXA1,BID,BRD4,CD44,HSPD1,CLTC,CLU,CYLD,DDIT3,DUSP1,EIF3A,HSP90B1,EZR,FLT3,GRB2,HNRNPU,HSPA8,HSPB1,HOXA5,NFKBIA,CXCL8,ITGA5,TCF4,LASP1,LDHA,LRRFIP1,MTDH,MAP3K1,MAP3K8,NCOA3,NUCKS1,PABPC1,POMP,PRKDC,PTPN1,RAB14,RAC1,RAP1A,RAP1B,RASSF1,RICTOR,RSF1,S100A11,SFPQ,SMAD3,SMC4,RBPJ,YY1,UCP2,ZBTB7A,ENO1,GNAS,CALR,CSF3R,GNAQ,EIF4EBP1,IL2RA,MDK,REL,RELB,QPRT,ACAP2,TNFAIP8,UBR5,HSH2D
Drug Inactivation by Structure Modification	6.30e-01	1.00e+00	848	27	1	23467	Malignant cells	GSTP1
Aberration of the Drug's Therapeutic Target	8.40e-01	1.00e+00	848	90	2	23467	Malignant cells	BRAF,FLT3
Epigenetic Alteration of DNA, RNA or Protein	9.40e-01	1.00e+00	848	455	11	23467	Malignant cells	BRAF,DNMT1,LMNA,TYMS,CXCL8,MAP3K8,RASSF1,SMC4,TIMP1,MALAT1,GDI2
Irregularity in Drug Uptake and Drug Efflux	1.00e+00	1.00e+00	848	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	3.70e-01	3.70e-01	504	186	5	23467	B cells	PARP1,ZEB2,HNRNPA2B1,LDHB,MALAT1
Regulation by the Disease Microenvironment	3.40e-01	3.40e-01	151	186	2	23467	CD4+ T cells	CXCR4,SOCS3
Regulation by the Disease Microenvironment	9.70e-01	9.70e-01	447	186	1	23467	CD8+ T cells	CXCR4
Regulation by the Disease Microenvironment	9.10e-01	9.10e-01	295	186	1	23467	Erythrocytes	LDHB
Regulation by the Disease Microenvironment	3.60e-01	3.60e-01	158	186	2	23467	NK cells	CXCR4,VIM

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	1.20e-23	6.10e-23	1932	781	151	23467	Malignant cells	BCL2L11,BAX,BCL11A,BCAT1,BRAF,CTSL,CCND2,CDK4,CDK6,TP53,CTNNB1,DNMT1,GAS7,GSTP1,HIF1A,HMGA1,HMGB1,HMOX1,HSPA1A,IDH2,ISG15,JUN,PKM,MCL1,MEF2D,MAP1LC3B,MYC,NFKB1,PARP1,PIK3CG,RALBP1,RPS6,S100A4,ST3GAL4,SOX4,STMN1,TET2,TYMS,VEGFA,VOPP1,ZEB2,YWHAZ,ADAM17,ATG3,ATG4B,ATM,BID,HSPA5,BNIP2,BTG1,CASP1,CCNG1,CD44,HSPD1,CLU,CAPNS1,CXCR4,CYLD,DCP2,DUSP1,EP300,EZR,FIS1,FLT3,FOXO3,FTL,FUS,GAPDH,G6PD,NR3C1,HAX1,HBEGF,HDAC1,HMGB2,HSPA8,HSPB1,HOXA5,IDH1,NFKBIA,IL18,CXCL8,ING4,ITGB1,KAT6A,KLF4,LDHA,LRRFIP1,MAP3K8,MDM2,MDM4,MGMT,MOB1A,MAP2K2,NUCKS1,PIK3R1,PABPC1,PGK1,AGPAT2,PRKDC,PSMB5,PTPN1,RAB14,RAC1,RASSF1,RAB27A,RICTOR,RRM1,S100A8,S100A11,SFPQ,SMAD3,SMC4,SOCS3,SOD2,SRI,RBPJ,TPT1,TMED3,TNFSF13B,TNFAIP3,TOM1,TOP1,TOP2B,TRIM27,UCP2,ULK1,ZBTB7A,ZKSCAN1,ENO1,PFKL,PFKFB3,GNAS,CD33,CALR,SMARCA4,NPM1,CEBPD,EIF4EBP1,INSIG1,RCN1,REL,RELB,SPTLC2,G3BP1,PMVK,OGA,HSH2D,CREBZF,APP,WTAP,BIRC2
Aberration of the Drug's Therapeutic Target	1.50e-02	3.80e-02	1932	90	14	23467	Malignant cells	BRAF,CDK4,CDK6,TP53,IDH2,BTK,CREBBP,FLT3,IDH1,MAP2K2,SF3B1,NPM1,COMT,AKR1B1
Drug Inactivation by Structure Modification	3.90e-01	6.40e-01	1932	27	3	23467	Malignant cells	GSTP1,SOD2,NME1
Irregularity in Drug Uptake and Drug Efflux	6.00e-01	7.50e-01	1932	37	3	23467	Malignant cells	ABCA1,ABCE1,SLC7A5
Epigenetic Alteration of DNA, RNA or Protein	9.70e-01	9.70e-01	1932	455	27	23467	Malignant cells	BCL2L11,BRAF,TP53,DNMT1,IDH2,EIF4G2,LMNA,TYMS,PMAIP1,ARID4B,CREBBP,CXCR4,FOXO3,GAPDH,IDH1,CXCL8,MAP3K8,RASSF1,SMC4,TIMP1,TNFSF13B,CYTOR,MALAT1,GDI2,PPP1R15A,NABP1,GABPB1-AS1

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	5.80e-01	5.80e-01	109	186	1	23467	B cells	PARP1
Regulation by the Disease Microenvironment	4.60e-03	4.60e-03	713	186	13	23467	CD4+ T cells	BCL2,BRAF,NFKB1,PARP1,CXCR4,PIK3CA,HNRNPA2B1,STAT3,VIM,ZEB1,LDHB,MALAT1,TSPYL2
Regulation by the Disease Microenvironment	3.90e-03	3.90e-03	617	186	12	23467	CD8+ T cells	BCL2,BRAF,CTNNB1,NFKB1,ZEB2,CXCR4,FYN,STAT3,VIM,LDHB,MALAT1,TSPYL2
Regulation by the Disease Microenvironment	2.10e-01	2.10e-01	821	186	9	23467	Erythrocytes	BCL2L1,CCNB1,EZH2,HMGB3,MTDH,QKI,HNRNPA2B1,VIM,LDHB
Regulation by the Disease Microenvironment	1.40e-01	1.40e-01	1059	186	12	23467	NK cells	BRAF,CTNNB1,NFKB1,PARP1,TGFB1,ZEB2,CX3CR1,HNRNPA2B1,STAT3,VIM,LDHB,TSPYL2

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
	taipale_tf_pairs__TEAD4_ELK1_RGAATSCGGAAGYN_CAP_repr	5.13	0.115	ELK1; TEAD4 (directAnnotation).	B cells
	transfac_pro__M06847	4.84	0.109	SALL3 (inferredBy_Orthology).	B cells
	transfac_pro__M05441	4.73	0.107	ZNF396 (directAnnotation).	B cells
	metacluster_10.48	4.5	0.103	ID2 (inferredBy_Orthology).	B cells
	transfac_pro__M05605	4.46	0.102	GATA6 (inferredBy_Orthology).	B cells
	transfac_pro__M04862	4.39	0.101	NRF1 (directAnnotation).	B cells
	flyfactorsurvey__Max_Mnt_SANGER_5_FBgn0017578	4.37	0.101	MAX (inferredBy_Orthology).	B cells
	taipale_tf_pairs__ERF_FOXI1_RSCGGATGTTKWN_CAP_repr	4.31	0.0997	ERF; FOXI1 (directAnnotation).	B cells
	transfac_pro__M06794	4.31	0.0996	ZNF107 (directAnnotation).	B cells
	metacluster_14.8	4.26	0.0987	MLX (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
	hocomoco__TYY2_HUMAN.H11MO.0.D	7.1	0.0808	YY2 (directAnnotation).	B cells
	metacluster_141.4	6.13	0.0734	GLIS2 (directAnnotation).	B cells
	taipale__YY2_DBD_NNCCGCCATNW_repr	5.96	0.072	YY2 (directAnnotation).	B cells
	metacluster_141.2	5.65	0.0696	E2F2; E2F3 (directAnnotation).	B cells
	hdpi__TP73	5.5	0.0685	TP73 (directAnnotation).	B cells
	flyfactorsurvey__pho_SOLEXA_F1-3	5.49	0.0684	YY1 (inferredBy_Orthology).	B cells
	metacluster_166.4	5.03	0.0649	BCLAF1; EHF; ELF1; ELF1; ELF1; ELF1; ELF1; ELF1; ELF2; ELF2; ELF4; ELK1; ELK1; ELK1; ELK1; ELK1; ELK1; ELK1; ELK1; ELK1; ELK3; ELK3; ELK3; ELK3; ELK4; ERG; ERG; ERG; ERG; ETS1; ETS1; ETS1; ETS1; ETS1; ETV1; ETV1; ETV1; ETV1; ETV2; ETV3; ETV4; ETV4; ETV4; ETV4; ETV4; ETV5; ETV7; FEV; FEV; FLI1; FLI1; FLI1; FLI1; GABPA; GABPA; GABPA; GABPA; GABPA; GABPA; GABPB1; GATAD1; PHF20; ZBTB25; ZBTB40 (directAnnotation). EHF; ELF1; ELF1; ELF3; ELF5; ELK3; ELK4; ERG; ETS1; ETV1; ETV2; ETV4; FLI1; GABPA; GABPA (inferredBy_Orthology).	B cells
	jaspar__MA1483.2	4.99	0.0646	ELF2 (directAnnotation).	B cells
	taipale_tf_pairs__ETS2_RCCGGAAGTG_HT	4.89	0.0638	ETS2 (directAnnotation).	B cells
	metacluster_172.6	4.77	0.0629	CHD2; E2F1 (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
	hdpi__FLI1	6.39	0.105	FLI1 (directAnnotation).	B cells
	taipale_tf_pairs__ELF2_NATGCGGAAGTR_HT	6.18	0.102	ELF2 (directAnnotation).	B cells
	taipale_tf_pairs__ETS2_RCCGGAAGTG_HT	6	0.1	ETS2 (directAnnotation).	B cells
	jaspar__MA1708.1	5.94	0.0991	ETV7 (directAnnotation).	B cells
	taipale_tf_pairs__ETV5_HOXA2_RSCGGWAATKR_CAP	5.64	0.0952	ETV5; HOXA2 (directAnnotation).	B cells
	taipale_tf_pairs__TEAD4_ETV1_RSCGGAAATRCM_CAP	5.49	0.0933	ETV1; TEAD4 (directAnnotation).	B cells
	jaspar__MA1483.2	5.17	0.0892	ELF2 (directAnnotation).	B cells
	taipale_tf_pairs__TEAD4_ERG_RSCGGAAATRCC_CAP	5.04	0.0874	ERG; TEAD4 (directAnnotation).	B cells
	taipale_tf_pairs__HOXB2_ETV1_ACCGGAAATGA_CAP	4.78	0.084	ETV1; HOXB2 (directAnnotation).	B cells
	taipale_tf_pairs__TEAD4_ERG_RSCGGAAATRCC_CAP_repr	4.73	0.0834	ERG; TEAD4 (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__M12602	6.17	0.446	ESR1 (directAnnotation).	B cells
	transfac_pro__M04960	6.02	0.436	POU5F1 (directAnnotation).	B cells
	tfdimers__MD00234	5.91	0.428	CDX2; TFAP2C (directAnnotation).	B cells
	tfdimers__MD00426	5.85	0.425	GFI1; GFI1B; SMAD4 (directAnnotation).	B cells
	taipale_tf_pairs__GCM1_ELF1_NRCCCRNNCGGAAGNN_CAP_repr	5.43	0.396	ELF1; GCM1 (directAnnotation).	B cells
	tfdimers__MD00481	5.22	0.382	MZF1; OVOL2 (directAnnotation).	B cells
	transfac_pro__M06194	5.22	0.382	ZNF121 (directAnnotation).	B cells
	transfac_pro__M08903	5.2	0.381	TEAD3 (directAnnotation).	B cells
	tfdimers__MD00214	5.15	0.377	CRX (directAnnotation).	B cells
	hocomoco__MXI1_MOUSE.H11MO.1.A	5.05	0.371	MXI1 (inferredBy_Orthology).	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
ETS1	metacluster_138.2	up	CD4+ T cells	post
ETS1	metacluster_166.4	up	CD4+ T cells	post
ETS1	metacluster_191.3	up	CD4+ T cells	post
ELF1	metacluster_138.2	down	CD4+ T cells	post
BCLAF1	metacluster_166.4	down	CD4+ T cells	post
ELF1	metacluster_166.4	down	CD4+ T cells	post
ELF1	taipale_tf_pairs__HOXB2_ELF1_NNYMATTANNNNNNNGGAAGNN_CAP_repr	down	CD4+ T cells	post
ELF1	metacluster_191.3	down	CD4+ T cells	post
JUN	metacluster_157.2	up	CD8+ T cells	post
JUNB	metacluster_157.2	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."