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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_PacAteTissue

Dataset summary for GSE169246_PacAteTissue

Datast information	Dataset	GSE169246_PacAteTissue
	PMID	34653365
	Raw data ID/link	NA
	Organism	Homo sapiens
	Source	patients
	Tissue	Tumor tissue
	Cancer type level1	Breast cancer
	Cancer type level2	Advanced triple-negative breast cancer (TNBC)
	Regimen	atezolizumab + paclitaxel
	Drug type	Immunotherapy
	Sample size	pre (resistant 5, sensitive 4); post (resistant 4, sensitive 2)
	Cell number	87713
	Extract protocol	10x genomics
	Data processing	CellRanger 3.0.0
	Public date	Public on Sep 15, 2021
	Description	This dataset has 9 patients, 6 of whom have both pre -and post-treatment samples.

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Drug summary for GSE169246_PacAteTissue

Drug name	DrugBank ID	Drug type	Targets name	Targets uniprot ID
"Atezolizumab"	DB11595	biotech	CD274; PDCD1	Q9NZQ7; Q15116
"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.)

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
IGKV1D-13	ENSG00000276566	3.91167	0.00e+00	0.00e+00	0.329	0.059	Plasma cells	pre
IGHV1-46	ENSG00000282131	3.59974	0.00e+00	0.00e+00	0.273	0.022	Plasma cells	pre
IGHA1	ENSG00000282633	2.23262	0.00e+00	0.00e+00	0.375	0.129	Plasma cells	pre
IGLV1-44	ENSG00000274854	2.09012	0.00e+00	0.00e+00	0.261	0.045	Plasma cells	pre
IGLV3-1	ENSG00000211673	1.81246	0.00e+00	0.00e+00	0.629	0.307	Plasma cells	pre
IGHG2	ENSG00000274497	1.71756	0.00e+00	0.00e+00	0.406	0.116	Plasma cells	pre
MT1X	ENSG00000187193	1.57974	0.00e+00	0.00e+00	0.406	0.141	Plasma cells	pre
IGHG4	ENSG00000277016	1.38447	0.00e+00	0.00e+00	0.504	0.169	Plasma cells	pre
IGLC2	ENSG00000211677	1.36757	8.56e-38	1.76e-33	0.506	0.254	Plasma cells	pre
MT2A	ENSG00000125148	1.28608	8.12e-29	1.67e-24	0.317	0.152	Plasma cells	pre
HLA-B	ENSG00000206450	1.24184	0.00e+00	0.00e+00	0.912	0.673	Plasma cells	pre
NEAT1	ENSG00000245532	1.23377	0.00e+00	0.00e+00	0.658	0.324	Plasma cells	pre
DNAAF1	ENSG00000154099	1.20228	0.00e+00	0.00e+00	0.384	0.085	Plasma cells	pre
IGKV1-9	ENSG00000282758	1.13929	1.36e-39	2.79e-35	0.285	0.095	Plasma cells	pre
IFI6	ENSG00000126709	1.03185	0.00e+00	0.00e+00	0.686	0.339	Plasma cells	pre
GADD45A	ENSG00000116717	0.949821	0.00e+00	0.00e+00	0.451	0.107	Plasma cells	pre
ISG15	ENSG00000187608	0.915304	6.35e-39	1.31e-34	0.376	0.171	Plasma cells	pre
MT-ATP8	ENSG00000228253	0.914344	6.05e-38	1.25e-33	0.824	0.649	Plasma cells	pre
IGLV6-57	ENSG00000211640	0.902826	3.79e-26	7.82e-22	0.258	0.107	Plasma cells	pre
SQSTM1	ENSG00000284099	0.825485	0.00e+00	6.08e-42	0.686	0.441	Plasma cells	pre
MT-ND5	ENSG00000198786	0.805043	0.00e+00	0.00e+00	0.848	0.598	Plasma cells	pre
MIR155HG	ENSG00000234883	0.785093	3.65e-31	7.52e-27	0.472	0.276	Plasma cells	pre
MALAT1	ENSG00000251562	0.770867	5.60e-07	1.15e-02	0.963	0.915	Plasma cells	pre
BTG2	ENSG00000159388	0.754115	5.18e-44	1.07e-39	0.689	0.476	Plasma cells	pre
IGKV3-20	ENSG00000282402	0.741922	0.00e+00	0.00e+00	0.538	0.254	Plasma cells	pre
HIST2H2AA4	NA	0.738999	0.00e+00	0.00e+00	0.381	0.1	Plasma cells	pre
MT-ND6	ENSG00000198695	0.733702	0.00e+00	0.00e+00	0.573	0.229	Plasma cells	pre
IGHGP	ENSG00000282094	0.730723	0.00e+00	0.00e+00	0.365	0.077	Plasma cells	pre
IFI27	ENSG00000275214	0.650647	4.83e-23	9.94e-19	0.373	0.212	Plasma cells	pre
JCHAIN	ENSG00000132465	0.61744	3.58e-36	7.37e-32	0.837	0.542	Plasma cells	pre
JSRP1	ENSG00000167476	0.602757	6.73e-44	1.37e-39	0.478	0.249	Plasma cells	pre
ZFP36	ENSG00000128016	0.577475	1.53e-21	3.15e-17	0.492	0.321	Plasma cells	pre
RGS1	ENSG00000090104	0.566839	8.36e-28	1.72e-23	0.594	0.402	Plasma cells	pre
RHOB	ENSG00000143878	0.562328	3.26e-30	6.73e-26	0.422	0.234	Plasma cells	pre
CYTOR	ENSG00000222041	0.521793	1.32e-23	2.72e-19	0.53	0.35	Plasma cells	pre
PDE4B	ENSG00000184588	0.50108	1.69e-16	3.47e-12	0.412	0.278	Plasma cells	pre
NFKBIA	ENSG00000100906	0.477559	1.87e-22	3.85e-18	0.48	0.308	Plasma cells	pre
PIM2	ENSG00000102096	0.472434	2.24e-34	4.62e-30	0.616	0.395	Plasma cells	pre
CCND2	ENSG00000118971	0.467465	0.00e+00	2.10e-44	0.263	0.069	Plasma cells	pre
ANKRD28	ENSG00000206560	0.465094	0.00e+00	5.38e-43	0.405	0.167	Plasma cells	pre
HSP90B1	ENSG00000166598	0.439049	6.48e-22	1.34e-17	0.906	0.801	Plasma cells	pre
RBM33	ENSG00000184863	0.432925	0.00e+00	1.46e-42	0.26	0.071	Plasma cells	pre
PRDM1	ENSG00000057657	0.43191	1.28e-27	2.65e-23	0.463	0.266	Plasma cells	pre
DERL3	ENSG00000274437	0.426657	9.86e-22	2.03e-17	0.837	0.729	Plasma cells	pre
KLF6	ENSG00000067082	0.418952	1.44e-22	2.96e-18	0.615	0.417	Plasma cells	pre
SDC1	ENSG00000115884	0.413276	0.00e+00	0.00e+00	0.451	0.174	Plasma cells	pre
IGKV1-39	ENSG00000282120	0.409655	4.67e-24	9.62e-20	0.427	0.205	Plasma cells	pre
TPM4	ENSG00000167460	0.409613	8.81e-21	1.81e-16	0.54	0.373	Plasma cells	pre
IGHG1	ENSG00000277633	0.406504	2.83e-13	5.82e-09	0.896	0.898	Plasma cells	pre
FNDC3B	ENSG00000075420	0.406405	8.16e-31	1.68e-26	0.393	0.199	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
GZMK	ENSG00000113088	-0.531266	1.30e-06	2.68e-02	0.311	0.455	NK cells	post
PNRC1	ENSG00000146278	-0.556865	4.58e-19	9.44e-15	0.775	0.921	NK cells	post
CXCR4	ENSG00000121966	-0.566301	5.09e-07	1.05e-02	0.85	0.843	NK cells	post
HSP90AB1	ENSG00000096384	-0.575079	2.56e-14	5.27e-10	0.848	0.955	NK cells	post
NFKB1	ENSG00000109320	-0.575319	5.62e-12	1.16e-07	0.426	0.657	NK cells	post
IL7R	ENSG00000168685	-0.576452	3.77e-09	7.76e-05	0.263	0.472	NK cells	post
ADGRE5	ENSG00000123146	-0.577775	1.51e-12	3.12e-08	0.524	0.708	NK cells	post
MT-ATP8	ENSG00000228253	-0.586306	1.38e-19	2.85e-15	0.964	0.989	NK cells	post
AHNAK	ENSG00000124942	-0.588415	7.74e-17	1.60e-12	0.368	0.64	NK cells	post
TNFAIP3	ENSG00000118503	-0.58881	5.62e-08	1.16e-03	0.775	0.899	NK cells	post
MT-CO3	ENSG00000198938	-0.593465	3.70e-25	7.62e-21	0.973	1	NK cells	post
EZR	ENSG00000092820	-0.594499	1.05e-09	2.17e-05	0.608	0.747	NK cells	post
MT-CYB	ENSG00000198727	-0.607146	4.64e-23	9.56e-19	0.987	1	NK cells	post
HLA-A	ENSG00000227715	-0.612483	1.95e-32	4.01e-28	0.996	1	NK cells	post
MALAT1	ENSG00000251562	-0.641359	6.20e-11	1.28e-06	1	1	NK cells	post
MT-ND4	ENSG00000198886	-0.651208	1.02e-24	2.09e-20	0.849	0.955	NK cells	post
NFKBIA	ENSG00000100906	-0.731527	9.22e-14	1.90e-09	0.597	0.803	NK cells	post
MYADM	ENSG00000179820	-0.760497	2.41e-13	4.97e-09	0.445	0.68	NK cells	post
CTSW	ENSG00000172543	-0.808862	1.08e-23	2.23e-19	0.621	0.904	NK cells	post
KLF2	ENSG00000127528	-0.828441	4.03e-21	8.31e-17	0.218	0.511	NK cells	post
LMNA	ENSG00000160789	-0.847639	2.59e-11	5.35e-07	0.362	0.573	NK cells	post
FTL	ENSG00000087086	1.75011	2.46e-27	5.07e-23	0.998	0.994	Mono/Macro	post
SPP1	ENSG00000118785	1.67395	2.24e-15	4.61e-11	0.306	0	Mono/Macro	post
IFI30	ENSG00000216490	1.64115	6.19e-39	1.27e-34	0.828	0.419	Mono/Macro	post
CTSD	ENSG00000117984	1.56933	6.91e-21	1.42e-16	0.723	0.348	Mono/Macro	post
APOC1	ENSG00000130208	1.44101	4.55e-15	9.37e-11	0.687	0.387	Mono/Macro	post
IFI27	ENSG00000275214	1.37226	4.36e-10	8.99e-06	0.393	0.142	Mono/Macro	post
IFI6	ENSG00000126709	1.25536	4.48e-25	9.24e-21	0.532	0.084	Mono/Macro	post
CSTB	ENSG00000160213	1.2204	2.78e-18	5.74e-14	0.844	0.606	Mono/Macro	post
CD9	ENSG00000010278	1.19145	1.01e-19	2.07e-15	0.566	0.155	Mono/Macro	post
C15orf48	ENSG00000166920	1.13432	2.32e-16	4.79e-12	0.598	0.213	Mono/Macro	post
S100A11	ENSG00000163191	1.12786	8.29e-37	1.71e-32	0.959	0.826	Mono/Macro	post
GLUL	ENSG00000135821	1.1044	8.86e-24	1.83e-19	0.763	0.394	Mono/Macro	post
FN1	ENSG00000115414	1.0996	7.98e-19	1.64e-14	0.371	0.006	Mono/Macro	post
LGALS1	ENSG00000100097	1.0293	5.14e-29	1.06e-24	0.934	0.574	Mono/Macro	post
APOE	ENSG00000130203	1.02355	8.10e-11	1.67e-06	0.677	0.419	Mono/Macro	post
GCHFR	ENSG00000137880	1.01017	7.31e-16	1.51e-11	0.379	0.052	Mono/Macro	post
IFITM3	ENSG00000142089	1.00052	2.56e-09	5.28e-05	0.638	0.419	Mono/Macro	post
NUPR1	ENSG00000176046	0.967538	7.19e-15	1.48e-10	0.517	0.161	Mono/Macro	post
TYROBP	ENSG00000011600	0.940939	2.04e-26	4.21e-22	0.946	0.832	Mono/Macro	post
CTSB	ENSG00000285132	0.928474	3.76e-16	7.76e-12	0.881	0.684	Mono/Macro	post
ISG15	ENSG00000187608	0.897658	1.05e-11	2.16e-07	0.345	0.077	Mono/Macro	post
FCGR3A	ENSG00000203747	0.890464	8.77e-20	1.81e-15	0.515	0.11	Mono/Macro	post
TREM2	ENSG00000095970	0.873	8.20e-20	1.69e-15	0.528	0.116	Mono/Macro	post
C1QB	ENSG00000173369	0.853832	1.53e-11	3.14e-07	0.66	0.387	Mono/Macro	post
HLA-C	ENSG00000206435	0.820063	7.18e-32	1.48e-27	0.997	0.974	Mono/Macro	post
OLR1	ENSG00000173391	0.806477	5.59e-20	1.15e-15	0.585	0.181	Mono/Macro	post
FTH1	ENSG00000167996	0.791918	1.25e-19	2.57e-15	1	1	Mono/Macro	post
ALOX5AP	ENSG00000132965	0.783321	1.05e-20	2.16e-16	0.473	0.052	Mono/Macro	post
CXCL2	ENSG00000081041	0.748436	2.50e-10	5.14e-06	0.426	0.148	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	1.80e-01	1.80e-01	182	186	3	23467	B cells	TGFB1,CXCR4,VIM
Regulation by the Disease Microenvironment	8.00e-02	8.00e-02	288	186	5	23467	CD4+ T cells	FYN,GATA3,STAT3,VIM,MALAT1
Regulation by the Disease Microenvironment	2.00e-01	2.00e-01	195	186	3	23467	CD8+ T cells	NFKB1,FYN,VIM
Regulation by the Disease Microenvironment	2.10e-01	2.10e-01	29	186	1	23467	Mast cells	MALAT1
Regulation by the Disease Microenvironment	6.00e-02	6.00e-02	264	186	5	23467	Mono_Macro	MMP9,IL1B,TGFBR1,VIM,TIMP2
Regulation by the Disease Microenvironment	5.60e-02	5.60e-02	181	186	4	23467	NK cells	NFKB1,TGFB1,FYN,MALAT1
Regulation by the Disease Microenvironment	1.00e+00	1.00e+00	59	186	0	23467	pDCs	NA
Regulation by the Disease Microenvironment	8.60e-02	8.60e-02	210	186	4	23467	Plasma cells	TP53INP1,CXCR4,RHOB,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
There is no signaficant down-regulated pathways in resistant group

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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	2.10e-02	2.10e-02	347	186	7	23467	B cells	NFKB1,PARP1,PTEN,CCNG2,HNRNPA2B1,SOCS3,LDHB
Regulation by the Disease Microenvironment	1.50e-01	1.50e-01	171	186	3	23467	CD4+ T cells	VIM,LDHB,MALAT1
Regulation by the Disease Microenvironment	1.90e-01	1.90e-01	190	186	3	23467	CD8+ T cells	CXCR4,VIM,MALAT1
Regulation by the Disease Microenvironment	1.00e+00	1.00e+00	29	186	0	23467	Mast cells	NA
Regulation by the Disease Microenvironment	9.20e-02	9.20e-02	215	186	4	23467	Mono_Macro	MMP9,HNRNPA2B1,VIM,TIMP2
Regulation by the Disease Microenvironment	6.60e-02	6.60e-02	117	186	3	23467	NK cells	NFKB1,CXCR4,MALAT1
Regulation by the Disease Microenvironment	1.00e+00	1.00e+00	15	186	0	23467	pDCs	NA
Regulation by the Disease Microenvironment	6.70e-01	6.70e-01	139	186	1	23467	Plasma cells	MTDH

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
	transfac_pro__M05513	4.06	0.0867	ZNF641 (inferredBy_Orthology).	B cells
	transfac_pro__M05352	4.04	0.0865	ZNF692 (inferredBy_Orthology).	B cells
	transfac_pro__M06257	4	0.0858	ZNF616 (directAnnotation).	B cells
	kznf__ZNF184_Schmitges2016_RCADE	3.99	0.0857	ZNF184 (directAnnotation).	B cells
	metacluster_103.2	3.96	0.0852	ZNF136; ZNF680 (directAnnotation).	B cells
	transfac_pro__M06952	3.94	0.0849	BATF (directAnnotation).	B cells
	transfac_pro__M06360	3.73	0.0818	ZNF626 (directAnnotation).	B cells
	transfac_pro__M01721	3.69	0.0812	PURA (directAnnotation).	B cells
	cisbp__M01738	3.68	0.081	BHLHE40 (inferredBy_Orthology).	B cells
	hocomoco__SMAD3_HUMAN.H11MO.0.B	3.68	0.081	SMAD3 (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__M05550	6.29	0.128	SNAPC4 (inferredBy_Orthology).	B cells
	jaspar__MA0604.1	5.39	0.113	ATF1 (inferredBy_Orthology).	B cells
	metacluster_21.5	5.11	0.109	HOXB2; HSF1; HSF1; HSF1; HSF1; HSF1; HSF1; HSF1; HSF1; HSF2; HSF2; HSF2; HSF2; HSF2; HSF2; HSF4; HSF4; HSF4 (directAnnotation). HSF1; HSF1; HSF1; HSF1; HSF1; HSF1; HSF1; HSF2; HSF2; HSF2; HSF2; HSF4; HSF4; HSF4; HSF4; HSF5; HSF5; HSF5; HSF5; HSFX1; HSFX1; HSFX1; HSFX1; HSFX2; HSFX2; HSFX2; HSFX2; HSFX3; HSFX3; HSFX3; HSFX3; HSFX4; HSFX4; HSFX4; HSFX4; HSFY1; HSFY1; HSFY1; HSFY1; HSFY2; HSFY2; HSFY2; HSFY2 (inferredBy_Orthology).	B cells
	metacluster_56.5	5.07	0.108	HSF1; HSF1; HSF2 (directAnnotation). HSF1; HSF2; HSF4; HSF5; HSFX1; HSFX2; HSFX3; HSFX4; HSFY1; HSFY2 (inferredBy_Orthology).	B cells
	metacluster_21.4	4.87	0.105	HSF1; HSF1; HSF2 (directAnnotation). HSF1; HSF2; HSF4; HSF5; HSFX1; HSFX2; HSFX3; HSFX4; HSFY1; HSFY2 (inferredBy_Orthology).	B cells
	transfac_public__M00039	4.86	0.105	CREB1 (directAnnotation).	B cells
	dbtfbs__GMEB1_K562_ENCSR928KOR_merged_N1	4.69	0.102	GMEB1 (directAnnotation).	B cells
	transfac_pro__M04826	4.64	0.101	EP300 (directAnnotation).	B cells
	transfac_pro__M05976	4.62	0.101	ZNF223 (directAnnotation).	B cells
	transfac_pro__M01861	4.49	0.0987	ATF1 (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_2.8	6.15	0.0952	IRF4; IRF5; IRF6; IRF9 (directAnnotation). IRF3; IRF5; IRF5; IRF6 (inferredBy_Orthology).	B cells
	dbtfbs__GMEB1_K562_ENCSR928KOR_merged_N1	5.78	0.0911	GMEB1 (directAnnotation).	B cells
	jaspar__MA0604.1	5.65	0.0897	ATF1 (inferredBy_Orthology).	B cells
	taipale_cyt_meth__CREB1_NRTGACGTN_eDBD_repr	5.35	0.0865	CREB1 (directAnnotation).	B cells
	metacluster_2.9	5.11	0.0837	IRF2; IRF2; IRF2; PRDM1; PRDM1 (directAnnotation). PRDM1 (inferredBy_Orthology).	B cells
	metacluster_22.25	4.98	0.0824	NFE2L2 (directAnnotation).	B cells
	metacluster_22.18	4.77	0.0801	BACH2 (inferredBy_Orthology).	B cells
	transfac_pro__M08803	4.73	0.0796	CREM (directAnnotation).	B cells
	kznf__ZNF613_Imbeault2017_RP_RCADE	4.61	0.0783	ZNF613 (directAnnotation).	B cells
	metacluster_22.29	4.58	0.078	NFE2 (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
	dbtfbs__ZNF407_representative_N1	4.03	0.1	ZNF407 (directAnnotation).	B cells
	metacluster_144.3	4.01	0.0997	ZNF704; ZNF704 (directAnnotation).	B cells
	transfac_pro__M12697	3.98	0.0993	ZNF142 (directAnnotation).	B cells
	metacluster_151.2	3.95	0.0987	ZNF23 (directAnnotation).	B cells
	cisbp__M00341	3.87	0.0974	PAX6 (directAnnotation).	B cells
	kznf__ZNF383_Imbeault2017_OM_RCADE	3.76	0.0956	ZNF383 (directAnnotation).	B cells
	kznf__ZNF730_Imbeault2017_RP_RCADE	3.75	0.0953	ZNF730 (directAnnotation).	B cells
	transfac_pro__M06035	3.73	0.095	ZNF749 (directAnnotation).	B cells
	metacluster_141.5	3.69	0.0944	NR3C1; THAP1; YY1; YY1; YY1; YY1; YY1; YY1; YY1; YY1; YY1; YY1; YY1; YY1; YY2; YY2; ZNF597 (directAnnotation). YY1; YY1; YY1; YY2; ZFP42 (inferredBy_Orthology).	B cells
	cisbp__M07938	3.68	0.0942	E2F1 (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
STAT1	metacluster_2.6	up	B cells	post
CREM	transfac_pro__M00801	up	B cells	post
IRF1	tfdimers__MD00026	up	B cells	post
IRF1	metacluster_2.7	up	B cells	post
IRF7	metacluster_2.7	up	B cells	post
STAT1	metacluster_2.7	up	B cells	post
STAT1	metacluster_38.1	up	B cells	post
KLF10	metacluster_170.2	up	B cells	post
KLF10	metacluster_163.1	up	B cells	post
EGR1	metacluster_55.3	up	B 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."