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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 (This dataset does not contain this module)
	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: GSE169246_PacBlood

Dataset summary for GSE169246_PacBlood

Datast information	Dataset	GSE169246_PacBlood
	PMID	34653365
	Raw data ID/link	NA
	Organism	Homo sapiens
	Source	patients
	Tissue	Peripheral blood mononuclear cells
	Cancer type level1	Breast cancer
	Cancer type level2	Advanced triple-negative breast cancer (TNBC)
	Regimen	paclitaxel
	Drug type	Chemotherapy
	Sample size	pre (resistant 4, sensitive 5); post (resistant 4, sensitive 5)
	Cell number	120823
	Extract protocol	10x genomics
	Data processing	CellRanger 3.0.0
	Public date	Public on Sep 15, 2021
	Description	This dataset has 9 patients with both pre -and post-treatment samples.

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Drug summary for GSE169246_PacBlood

Drug name	DrugBank ID	Drug type	Targets name	Targets uniprot ID
"Paclitaxel"	DB01229	small molecule	TUBB1; BCL2; MAP4; MAP2; MAPT; NR1I2	Q9H4B7; P10415; P27816; P11137; P10636; 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.)

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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
HBB	ENSG00000244734	1.93383	2.04e-29	4.02e-25	0.524	0	Plasma cells	pre
JUN	ENSG00000177606	0.975496	2.66e-12	5.25e-08	0.462	0.141	Plasma cells	pre
CITED2	ENSG00000164442	0.927847	3.63e-13	7.17e-09	0.566	0.214	Plasma cells	pre
TXNIP	ENSG00000265972	0.859276	4.91e-14	9.70e-10	0.476	0.125	Plasma cells	pre
MT-ND6	ENSG00000198695	0.854307	1.28e-13	2.52e-09	0.828	0.49	Plasma cells	pre
KLF2	ENSG00000127528	0.812314	1.40e-13	2.75e-09	0.634	0.255	Plasma cells	pre
MT-ND5	ENSG00000198786	0.775127	4.00e-11	7.89e-07	0.979	0.844	Plasma cells	pre
HSPA8	ENSG00000109971	0.698785	2.28e-09	4.50e-05	0.828	0.568	Plasma cells	pre
HLA-DQA1	ENSG00000236418	0.623016	1.22e-12	2.41e-08	0.49	0.141	Plasma cells	pre
MT-ATP8	ENSG00000228253	0.618554	9.71e-10	1.92e-05	0.979	0.802	Plasma cells	pre
MT-ND4L	ENSG00000212907	0.603534	1.30e-10	2.56e-06	0.993	0.891	Plasma cells	pre
TSC22D3	ENSG00000157514	0.571063	3.21e-10	6.34e-06	0.303	0.052	Plasma cells	pre
TXNDC5	ENSG00000239264	0.552824	1.34e-06	2.65e-02	0.917	0.88	Plasma cells	pre
PABPC1	ENSG00000070756	0.49586	5.83e-08	1.15e-03	0.821	0.604	Plasma cells	pre
DDX5	ENSG00000108654	0.447333	4.57e-07	9.01e-03	0.531	0.276	Plasma cells	pre
EEF2	ENSG00000167658	0.437734	9.76e-08	1.93e-03	0.959	0.911	Plasma cells	pre
TSPO	ENSG00000100300	0.425615	8.87e-08	1.75e-03	0.31	0.089	Plasma cells	pre
AQP3	ENSG00000165272	0.420517	5.67e-07	1.12e-02	0.821	0.63	Plasma cells	pre
CDKN1B	ENSG00000111276	0.419267	6.02e-11	1.19e-06	0.317	0.052	Plasma cells	pre
MT-CO1	ENSG00000198804	0.413841	6.40e-07	1.26e-02	1	0.99	Plasma cells	pre
PNRC1	ENSG00000146278	0.411811	3.97e-08	7.83e-04	0.338	0.099	Plasma cells	pre
SFPQ	ENSG00000116560	0.41093	4.61e-07	9.11e-03	0.462	0.208	Plasma cells	pre
TRIB1	ENSG00000173334	0.377573	1.09e-09	2.15e-05	0.379	0.104	Plasma cells	pre
MYO1D	ENSG00000176658	0.357748	4.63e-08	9.14e-04	0.379	0.13	Plasma cells	pre
LRP10	ENSG00000197324	0.323753	7.60e-07	1.50e-02	0.366	0.141	Plasma cells	pre
KCNA3	ENSG00000177272	0.309052	6.14e-07	1.21e-02	0.455	0.203	Plasma cells	pre
UBE2J1	ENSG00000198833	0.29169	7.71e-07	1.52e-02	0.966	0.995	Plasma cells	pre
GAB1	ENSG00000109458	0.285054	1.95e-06	3.85e-02	0.303	0.099	Plasma cells	pre
NDUFC2	ENSG00000151366	-0.271869	8.94e-07	1.76e-02	0.083	0.302	Plasma cells	pre
DPM3	ENSG00000179085	-0.303108	5.21e-07	1.03e-02	0.159	0.417	Plasma cells	pre
PET100	ENSG00000229833	-0.309789	5.09e-08	1.00e-03	0.193	0.479	Plasma cells	pre
NDUFAF3	ENSG00000178057	-0.311469	1.49e-06	2.93e-02	0.331	0.594	Plasma cells	pre
FAU	ENSG00000149806	-0.31243	2.19e-06	4.32e-02	0.959	0.979	Plasma cells	pre
NDUFA11	ENSG00000174886	-0.326929	2.29e-07	4.52e-03	0.159	0.427	Plasma cells	pre
RPS19	ENSG00000105372	-0.336713	1.23e-06	2.42e-02	0.986	0.995	Plasma cells	pre
RPL35A	ENSG00000182899	-0.355845	1.36e-06	2.69e-02	0.931	0.948	Plasma cells	pre
ELOB	ENSG00000103363	-0.362773	2.27e-06	4.48e-02	0.607	0.771	Plasma cells	pre
CBWD1	NA	-0.364565	2.69e-07	5.31e-03	0.145	0.391	Plasma cells	pre
RABAC1	ENSG00000105404	-0.367263	7.35e-07	1.45e-02	0.814	0.911	Plasma cells	pre
NAA38	ENSG00000183011	-0.373226	1.81e-06	3.57e-02	0.221	0.458	Plasma cells	pre
SEC61B	ENSG00000106803	-0.380381	1.93e-07	3.81e-03	0.924	0.943	Plasma cells	pre
NDUFB4	ENSG00000065518	-0.381626	5.07e-07	1.00e-02	0.545	0.75	Plasma cells	pre
BST2	ENSG00000130303	-0.388496	1.95e-06	3.85e-02	0.31	0.542	Plasma cells	pre
RPL39	ENSG00000198918	-0.393024	1.86e-09	3.66e-05	0.938	0.958	Plasma cells	pre
NDUFB1	ENSG00000183648	-0.401067	5.82e-08	1.15e-03	0.145	0.406	Plasma cells	pre
RPL34	ENSG00000109475	-0.401235	2.53e-09	5.00e-05	0.931	0.984	Plasma cells	pre
COX7C	ENSG00000127184	-0.408688	9.24e-07	1.82e-02	0.69	0.828	Plasma cells	pre
RPLP2	ENSG00000177600	-0.410747	7.04e-07	1.39e-02	0.945	0.948	Plasma cells	pre
NDUFA3	ENSG00000276061	-0.410864	1.56e-08	3.08e-04	0.276	0.573	Plasma cells	pre
UBL5	ENSG00000198258	-0.412743	4.99e-08	9.85e-04	0.483	0.734	Plasma 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
CD52	ENSG00000169442	0.282314	2.37e-18	4.68e-14	0.707	0.635	Mono/Macro	post
PSMB9	ENSG00000239836	0.270702	1.06e-42	2.09e-38	0.773	0.682	Mono/Macro	post
CPVL	ENSG00000106066	0.266628	3.19e-33	6.30e-29	0.688	0.612	Mono/Macro	post
MT-ATP8	ENSG00000228253	0.266358	1.44e-15	2.85e-11	0.958	0.964	Mono/Macro	post
RPS26	ENSG00000197728	0.251609	2.10e-26	4.14e-22	0.926	0.931	Mono/Macro	post
TPM4	ENSG00000167460	-0.252167	4.20e-44	8.24e-40	0.377	0.525	Mono/Macro	post
STAB1	ENSG00000010327	-0.257786	0.00e+00	0.00e+00	0.252	0.407	Mono/Macro	post
LST1	ENSG00000235915	-0.264304	1.84e-23	3.63e-19	0.943	0.959	Mono/Macro	post
ID2	ENSG00000115738	-0.26504	2.24e-12	4.43e-08	0.319	0.379	Mono/Macro	post
CSTB	ENSG00000160213	-0.267515	2.72e-43	5.38e-39	0.673	0.792	Mono/Macro	post
UBE2J1	ENSG00000198833	-0.2683	0.00e+00	0.00e+00	0.323	0.512	Mono/Macro	post
MT-ND5	ENSG00000198786	-0.274137	0.00e+00	0.00e+00	0.961	0.983	Mono/Macro	post
BTG2	ENSG00000159388	-0.279918	0.00e+00	0.00e+00	0.319	0.479	Mono/Macro	post
S100A4	ENSG00000196154	-0.283371	0.00e+00	0.00e+00	0.999	1	Mono/Macro	post
SULT1A1	ENSG00000196502	-0.28497	0.00e+00	1.01e-41	0.437	0.575	Mono/Macro	post
FCN1	ENSG00000085265	-0.293334	0.00e+00	0.00e+00	0.975	0.976	Mono/Macro	post
SRGN	ENSG00000122862	-0.297685	0.00e+00	0.00e+00	0.963	0.98	Mono/Macro	post
MCL1	ENSG00000143384	-0.298215	7.71e-40	1.52e-35	0.713	0.791	Mono/Macro	post
TUBA1A	ENSG00000167552	-0.298528	7.08e-38	1.40e-33	0.576	0.684	Mono/Macro	post
H1FX	NA	-0.29963	5.63e-26	1.11e-21	0.471	0.562	Mono/Macro	post
BCL2A1	ENSG00000140379	-0.303733	0.00e+00	3.18e-43	0.369	0.524	Mono/Macro	post
MALAT1	ENSG00000251562	-0.304321	6.30e-27	1.24e-22	1	0.999	Mono/Macro	post
ISG15	ENSG00000187608	-0.304889	5.10e-21	1.01e-16	0.556	0.668	Mono/Macro	post
CD83	ENSG00000112149	-0.312246	0.00e+00	0.00e+00	0.076	0.26	Mono/Macro	post
RHOB	ENSG00000143878	-0.31912	8.13e-28	1.61e-23	0.434	0.544	Mono/Macro	post
MT-ND6	ENSG00000198695	-0.326566	0.00e+00	2.00e-43	0.416	0.568	Mono/Macro	post
BLOC1S1	ENSG00000135441	-0.32674	0.00e+00	0.00e+00	0.309	0.554	Mono/Macro	post
CDKN1A	ENSG00000124762	-0.328175	0.00e+00	0.00e+00	0.222	0.404	Mono/Macro	post
IFITM2	ENSG00000185201	-0.33796	0.00e+00	0.00e+00	0.902	0.959	Mono/Macro	post
VIM	ENSG00000026025	-0.3394	0.00e+00	0.00e+00	0.995	0.995	Mono/Macro	post
AC020916.1	NA	-0.340683	0.00e+00	0.00e+00	0.082	0.3	Mono/Macro	post
SH3BGRL3	ENSG00000142669	-0.341765	0.00e+00	0.00e+00	0.996	0.999	Mono/Macro	post
ATP2B1-AS1	ENSG00000271614	-0.344314	0.00e+00	0.00e+00	0.36	0.554	Mono/Macro	post
IFI44L	ENSG00000137959	-0.346682	0.00e+00	0.00e+00	0.431	0.591	Mono/Macro	post
RPL36A	ENSG00000241343	-0.35733	0.00e+00	0.00e+00	0.705	0.853	Mono/Macro	post
IFITM1	ENSG00000185885	-0.367993	2.42e-38	4.78e-34	0.418	0.546	Mono/Macro	post
JUND	ENSG00000130522	-0.368741	0.00e+00	0.00e+00	0.434	0.623	Mono/Macro	post
KLF4	ENSG00000136826	-0.371504	0.00e+00	0.00e+00	0.333	0.546	Mono/Macro	post
MAFB	ENSG00000204103	-0.381569	0.00e+00	0.00e+00	0.58	0.724	Mono/Macro	post
KLF2	ENSG00000127528	-0.397286	2.52e-44	4.97e-40	0.638	0.732	Mono/Macro	post
APOBEC3A	ENSG00000262156	-0.400382	0.00e+00	1.24e-42	0.379	0.536	Mono/Macro	post
NFKBIZ	ENSG00000144802	-0.403291	0.00e+00	0.00e+00	0.366	0.596	Mono/Macro	post
CEBPB	ENSG00000172216	-0.412172	0.00e+00	0.00e+00	0.714	0.83	Mono/Macro	post
CCNL1	ENSG00000163660	-0.417181	0.00e+00	0.00e+00	0.42	0.652	Mono/Macro	post
S100A12	ENSG00000163221	-0.424831	1.56e-06	3.07e-02	0.71	0.697	Mono/Macro	post
SAT1	ENSG00000130066	-0.426851	0.00e+00	0.00e+00	0.974	0.981	Mono/Macro	post
IFI6	ENSG00000126709	-0.426922	0.00e+00	0.00e+00	0.664	0.807	Mono/Macro	post
IL1B	ENSG00000125538	-0.435044	0.00e+00	0.00e+00	0.105	0.3	Mono/Macro	post
IFITM3	ENSG00000142089	-0.43877	0.00e+00	0.00e+00	0.902	0.962	Mono/Macro	post
ZFP36L1	ENSG00000185650	-0.447149	0.00e+00	9.81e-45	0.653	0.75	Mono/Macro	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 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-03	3.70e-03	384	186	9	23467	B cells	BCL2,CDKN1B,NFKB1,TGFBR2,ZEB2,PDCD6IP,HNRNPA2B1,VIM,MALAT1
Regulation by the Disease Microenvironment	4.00e-02	4.00e-02	399	186	7	23467	CD4+ T cells	BCL2,CDKN1B,NFKB1,TGFBR2,CXCR4,HNRNPA2B1,MALAT1
Regulation by the Disease Microenvironment	6.10e-01	6.10e-01	257	186	2	23467	CD8+ T cells	CDKN1B,CXCR4
Regulation by the Disease Microenvironment	2.90e-01	2.90e-01	454	186	5	23467	cDCs	NFKB1,TGFBR2,ZEB2,HNRNPA2B1,VIM
Regulation by the Disease Microenvironment	1.40e-01	1.40e-01	442	186	6	23467	Mono_Macro	TGFB1,TGFBR2,ZEB2,HNRNPA2B1,VIM,MALAT1
Regulation by the Disease Microenvironment	1.50e-01	1.50e-01	548	186	7	23467	NK cells	CDKN1B,TGFBR2,ZEB2,CX3CR1,PDCD6IP,HNRNPA2B1,STAT3
Regulation by the Disease Microenvironment	2.10e-01	2.10e-01	199	186	3	23467	pDCs	HNRNPA2B1,SMAD3,TSPYL2
Regulation by the Disease Microenvironment	5.30e-01	5.30e-01	94	186	1	23467	Plasma cells	CDKN1B

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 1 known drug resistance mechanisms in TME cells

Mechnism	Pval	FDR	Signature	Geneset	Overlap	Background	Cell type	Enriched Genes
Regulation by the Disease Microenvironment	3.60e-01	3.60e-01	160	186	2	23467	B cells	HNRNPA2B1,MALAT1
Regulation by the Disease Microenvironment	2.30e-02	2.30e-02	77	186	3	23467	CD4+ T cells	VIM,LDHB,MALAT1
Regulation by the Disease Microenvironment	4.00e-02	4.00e-02	235	186	5	23467	CD8+ T cells	CXCR4,HNRNPA2B1,VIM,LDHB,MALAT1
Regulation by the Disease Microenvironment	5.20e-01	5.20e-01	348	186	3	23467	cDCs	TGFB1,VIM,MALAT1
Regulation by the Disease Microenvironment	5.50e-03	5.50e-03	89	186	4	23467	Mono_Macro	IL1B,RHOB,VIM,MALAT1
Regulation by the Disease Microenvironment	6.30e-01	6.30e-01	123	186	1	23467	NK cells	MALAT1
Regulation by the Disease Microenvironment	1.00e+00	1.00e+00	1	186	0	23467	pDCs	NA
Regulation by the Disease Microenvironment	3.90e-01	3.90e-01	169	186	2	23467	Plasma cells	RHOB,MALAT1
Regulation by the Disease Microenvironment	1.50e-01	1.50e-01	88	186	2	23467	Progenitors	LDHB,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
This dataset does not contain malignant cells, nor does it predict any miRNA that corresponds to the top10 DEGs.	This dataset does not contain malignant cells, nor does it predict any miRNA that corresponds to the top10 DEGs.

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 does not contain malignant cells, nor does it predict any miRNA that corresponds to the top10 DEGs.	This dataset does not contain malignant cells, nor does it predict any miRNA that corresponds to the top10 DEGs.

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
	hdpi__NRL	3.49	0.104	NRL (directAnnotation).	B cells
	flyfactorsurvey__Mad_FlyReg_FBgn0011648	3.41	0.103	SMAD9 (inferredBy_Orthology).	B cells
	cisbp__M00341	3.41	0.103	PAX6 (directAnnotation).	B cells
	cisbp__M00968	3.37	0.102	MTF2 (directAnnotation).	B cells
	metacluster_141.6	3.28	0.1	MZF1; TAF1; YY1; YY1; YY1; YY1; YY1; YY1; YY1; YY1; YY1; YY1; YY1; YY1; YY2; YY2; ZFP42; ZFP42; ZFP42; ZFP42; ZFP42; ZFP42; ZNF597 (directAnnotation). TAF1; TAF1L (inferredBy_Orthology).	B cells
	hdpi__FEZF2	3.27	0.1	FEZF2 (directAnnotation).	B cells
	hocomoco__TYY2_HUMAN.H11MO.0.D	3.26	0.0998	YY2 (directAnnotation).	B cells
	transfac_pro__M07310	3.23	0.0992	SP5 (directAnnotation).	B cells
	metacluster_67.2	3.19	0.0984	ZNF501 (directAnnotation). ACAA1; E2F2; E2F2; E2F3; E2F3; FOXN4 (inferredBy_Orthology).	B cells
	homer__TWVGGTCCGC_HINFP	3.18	0.0983	HINFP (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
	transfac_pro__M06404	7.69	0.0949	ZNF497 (directAnnotation).	B cells
	swissregulon__hs__ETV6	6.21	0.0788	ETV6 (directAnnotation).	B cells
	metacluster_140.1	4.59	0.0612	BCL11B; BCL11B (directAnnotation).	B cells
	transfac_pro__M05711	4.57	0.061	ZNF37A (directAnnotation).	B cells
	taipale_tf_pairs__GCM1_ETV4_RTGCGGGCGGAAGTR_CAP	4.51	0.0603	ETV4; GCM1 (directAnnotation).	B cells
	cisbp__M02645	4.44	0.0596	ETS1 (directAnnotation).	B cells
	transfac_pro__M04923	4.42	0.0594	ZBTB33 (directAnnotation).	B cells
	taipale_tf_pairs__GCM2_PITX1_RTRCGGGSGATTAN_CAP_repr	4.37	0.0589	GCM2; PITX1 (directAnnotation).	B cells
	transfac_pro__M06322	4.36	0.0588	ZNF181 (directAnnotation).	B cells
	taipale_tf_pairs__ERF_HOXA3_RSCGGAWNNNNNNNYMATTA_CAP_repr	4.33	0.0584	ERF; HOXA3 (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
	metacluster_141.4	7.77	0.136	GLIS2 (directAnnotation).	B cells
	hocomoco__TYY2_HUMAN.H11MO.0.D	6.74	0.122	YY2 (directAnnotation).	B cells
	taipale__YY2_DBD_NNCCGCCATNW_repr	5.87	0.109	YY2 (directAnnotation).	B cells
	transfac_pro__M06259	5.06	0.0982	ZNF91 (directAnnotation).	B cells
	metacluster_141.2	5.05	0.0979	E2F2; E2F3 (directAnnotation).	B cells
	tfdimers__MD00351	4.69	0.093	IRF8; RFX1; RFX2; RFX3; RFX4; RFX5; RFXANK; RFXAP (directAnnotation).	B cells
	flyfactorsurvey__pho_SOLEXA_F1-3	4.63	0.0921	YY1 (inferredBy_Orthology).	B cells
	metacluster_2.8	4.27	0.0872	IRF4; IRF5; IRF6; IRF9 (directAnnotation). IRF3; IRF5; IRF5; IRF6 (inferredBy_Orthology).	B cells
	transfac_pro__M06715	3.64	0.0784	ZNF331 (directAnnotation).	B cells
	stark__RCGCMATTW	3.63	0.0783	YY1 (inferredBy_Orthology).	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
	swissregulon__hs__ETV6	7.27	0.123	ETV6 (directAnnotation).	B cells
	hdpi__FLI1	7.2	0.122	FLI1 (directAnnotation).	B cells
	metacluster_2.7	6.53	0.111	IRF1; IRF1; IRF2; IRF2; IRF3; IRF4; IRF5; IRF6; IRF7; IRF7; IRF8; IRF8; IRF9; PRDM1; PRDM1; PRDM1; PRDM1; PRDM1; PRDM1; PRDM1; PRDM1; PRDM1; PRDM1; PRDM1; PRDM1; STAT1; STAT1; STAT2 (directAnnotation). PRDM1; PRDM1; PRDM1 (inferredBy_Orthology).	B cells
	metacluster_2.6	5.92	0.102	IRF1; IRF1; IRF1; IRF1; IRF1; IRF1; IRF1; IRF1; IRF1; IRF1; IRF2; IRF2; IRF2; IRF2; IRF2; IRF2; IRF2; IRF3; IRF3; IRF3; IRF3; IRF3; IRF3; IRF4; IRF4; IRF4; IRF4; IRF4; IRF5; IRF5; IRF5; IRF5; IRF5; IRF5; IRF5; IRF6; IRF7; IRF7; IRF7; IRF7; IRF7; IRF7; IRF7; IRF8; IRF8; IRF8; IRF8; IRF8; IRF8; IRF8; IRF8; IRF9; IRF9; IRF9; IRF9; IRF9; IRF9; IRF9; STAT1; STAT2; STAT2; STAT2; STAT2; ZNF426; ZNF71 (directAnnotation). IRF1; IRF1; IRF3; IRF8 (inferredBy_Orthology).	B cells
	transfac_pro__M06763	5.43	0.0949	ZNF225 (directAnnotation).	B cells
	transfac_pro__M04887	5.16	0.091	TCF12 (directAnnotation).	B cells
	metacluster_2.8	5	0.0885	IRF4; IRF5; IRF6; IRF9 (directAnnotation). IRF3; IRF5; IRF5; IRF6 (inferredBy_Orthology).	B cells
	metacluster_79.12	4.82	0.0859	ZNF257 (directAnnotation).	B cells
	jaspar__MA1509.1	4.75	0.0847	IRF6 (directAnnotation).	B cells
	metacluster_161.15	4.73	0.0845	NKX3-1 (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
JUNB	metacluster_137.2	up	CD8+ T cells	post
CEBPD	taipale_tf_pairs__ETV2_CEBPD_RSCGGANNTTGCGYAAN_CAP_repr	up	cDCs	post
SPI1	metacluster_167.5	up	cDCs	post
FOS	tfdimers__MD00165	down	Mono/Macro	post
FOSB	tfdimers__MD00165	down	Mono/Macro	post
JUN	tfdimers__MD00165	down	Mono/Macro	post
JUNB	tfdimers__MD00165	down	Mono/Macro	post
JUND	tfdimers__MD00165	down	Mono/Macro	post
CEBPB	taipale_tf_pairs__GCM1_CEBPB_ATRSGGGNNNNTTRCGYAAN_CAP_repr	down	Mono/Macro	post
CEBPB	tfdimers__MD00359	down	Mono/Macro	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."