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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
IFI6	ENSG00000126709	1.55119	0.00e+00	0.00e+00	0.717	0.053	Plasma cells	post
IGHG1	ENSG00000277633	1.36472	7.51e-12	1.55e-07	0.824	0.868	Plasma cells	post
HLA-B	ENSG00000206450	1.0908	1.36e-33	2.80e-29	0.945	0.694	Plasma cells	post
IGHGP	ENSG00000282094	1.08391	1.26e-15	2.59e-11	0.394	0.099	Plasma cells	post
IFI27	ENSG00000275214	1.06842	4.36e-25	8.98e-21	0.342	0.02	Plasma cells	post
IGHG4	ENSG00000277016	1.03767	1.11e-15	2.29e-11	0.544	0.22	Plasma cells	post
IFITM1	ENSG00000185885	0.866397	1.03e-28	2.12e-24	0.524	0.102	Plasma cells	post
SQSTM1	ENSG00000284099	0.855623	5.41e-10	1.12e-05	0.638	0.48	Plasma cells	post
NEAT1	ENSG00000245532	0.838952	4.90e-08	1.01e-03	0.651	0.48	Plasma cells	post
MIR155HG	ENSG00000234883	0.772764	3.89e-12	8.02e-08	0.384	0.141	Plasma cells	post
ISG15	ENSG00000187608	0.719153	7.90e-22	1.63e-17	0.332	0.033	Plasma cells	post
JSRP1	ENSG00000167476	0.650994	2.09e-09	4.31e-05	0.541	0.345	Plasma cells	post
PPP1R15A	ENSG00000087074	0.59857	5.80e-10	1.20e-05	0.508	0.289	Plasma cells	post
CDKN1A	ENSG00000124762	0.587697	7.89e-10	1.63e-05	0.42	0.211	Plasma cells	post
SDC1	ENSG00000115884	0.583947	4.99e-22	1.03e-17	0.528	0.171	Plasma cells	post
MT-ND5	ENSG00000198786	0.571419	1.55e-08	3.19e-04	0.795	0.622	Plasma cells	post
CYTOR	ENSG00000222041	0.545642	2.32e-08	4.79e-04	0.564	0.378	Plasma cells	post
TRIB1	ENSG00000173334	0.522659	3.50e-13	7.22e-09	0.469	0.211	Plasma cells	post
PECAM1	ENSG00000261371	0.512269	1.01e-23	2.08e-19	0.42	0.072	Plasma cells	post
ANKRD28	ENSG00000206560	0.494396	2.44e-10	5.03e-06	0.528	0.286	Plasma cells	post
PTP4A3	ENSG00000275575	0.465205	1.07e-18	2.21e-14	0.251	0.01	Plasma cells	post
GAS6	ENSG00000183087	0.451918	3.08e-20	6.34e-16	0.492	0.148	Plasma cells	post
FOSB	ENSG00000125740	0.43585	1.55e-07	3.20e-03	0.541	0.319	Plasma cells	post
MIR4435-2HG	ENSG00000172965	0.422109	4.48e-10	9.23e-06	0.332	0.128	Plasma cells	post
SPAG4	ENSG00000061656	0.380464	2.64e-12	5.44e-08	0.407	0.161	Plasma cells	post
TYMP	ENSG00000025708	0.37021	1.24e-14	2.55e-10	0.29	0.056	Plasma cells	post
CFLAR	ENSG00000003402	0.364042	7.11e-08	1.46e-03	0.371	0.191	Plasma cells	post
HLA-C	ENSG00000206435	0.347528	7.31e-08	1.51e-03	0.964	0.964	Plasma cells	post
LGALS1	ENSG00000100097	0.30613	1.96e-06	4.04e-02	0.264	0.112	Plasma cells	post
IRF7	ENSG00000276561	0.290687	2.87e-08	5.91e-04	0.287	0.112	Plasma cells	post
MANEA	ENSG00000172469	-0.251591	8.93e-09	1.84e-04	0.101	0.283	Plasma cells	post
PTGES3	ENSG00000110958	-0.253238	6.28e-08	1.29e-03	0.104	0.276	Plasma cells	post
CTSS	ENSG00000163131	-0.253838	7.52e-09	1.55e-04	0.081	0.253	Plasma cells	post
RBM3	ENSG00000102317	-0.257513	4.10e-09	8.45e-05	0.075	0.25	Plasma cells	post
NPM1	ENSG00000181163	-0.264767	5.58e-07	1.15e-02	0.134	0.306	Plasma cells	post
JUND	ENSG00000130522	-0.267123	5.24e-07	1.08e-02	0.163	0.342	Plasma cells	post
SEC14L1	ENSG00000129657	-0.269209	5.91e-08	1.22e-03	0.156	0.342	Plasma cells	post
EIF2AK4	ENSG00000128829	-0.271819	2.23e-07	4.59e-03	0.156	0.329	Plasma cells	post
TRMT112	ENSG00000173113	-0.275835	3.20e-10	6.59e-06	0.121	0.336	Plasma cells	post
HINT1	ENSG00000169567	-0.278583	3.54e-08	7.29e-04	0.098	0.273	Plasma cells	post
REEP5	ENSG00000129625	-0.28558	1.81e-07	3.72e-03	0.199	0.382	Plasma cells	post
PNRC1	ENSG00000146278	-0.286898	1.85e-07	3.82e-03	0.091	0.25	Plasma cells	post
RNGTT	ENSG00000111880	-0.289245	2.92e-08	6.02e-04	0.085	0.25	Plasma cells	post
RPN1	ENSG00000163902	-0.291789	5.60e-07	1.15e-02	0.29	0.47	Plasma cells	post
TMED9	ENSG00000184840	-0.292046	2.34e-07	4.83e-03	0.322	0.513	Plasma cells	post
EAF2	ENSG00000145088	-0.29261	5.45e-09	1.12e-04	0.147	0.349	Plasma cells	post
TCEA1	ENSG00000187735	-0.298116	3.67e-10	7.56e-06	0.078	0.266	Plasma cells	post
MZT2B	ENSG00000152082	-0.304844	1.08e-13	2.23e-09	0.062	0.296	Plasma cells	post
NCF1	ENSG00000158517	-0.306695	8.59e-09	1.77e-04	0.107	0.293	Plasma cells	post
LMAN2	ENSG00000169223	-0.307017	2.44e-07	5.02e-03	0.358	0.543	Plasma 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 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
	swissregulon__hs__ZNF8	3.03	0.0866	ZNF8 (directAnnotation).	Mast cells
	metacluster_126.11	3.03	0.0865	ZNF286A (directAnnotation).	Mast cells
	metacluster_86.2	3.02	0.0864	ZNF45 (directAnnotation).	Mast cells
	taipale_tf_pairs__ETV2_FOXI1_RSCGGATGTTKW_CAP	3.01	0.0861	ETV2; FOXI1 (directAnnotation).	Mast cells
	taipale__YY2_DBD_NNCCGCCATNW_repr	6.37	0.104	YY2 (directAnnotation).	Mono/Macro
	hocomoco__TYY2_HUMAN.H11MO.0.D	6.19	0.102	YY2 (directAnnotation).	Mono/Macro
	transfac_pro__M05862	5.44	0.0922	ZNF615 (directAnnotation).	Mono/Macro
	taipale_tf_pairs__HOXD12_ETV4_RSCGGAAGTAATAAAN_CAP	4.88	0.0849	ETV4; HOXD12 (directAnnotation).	Mono/Macro
	cisbp__M02645	4.37	0.0783	ETS1 (directAnnotation).	Mono/Macro
	metacluster_111.6	4.36	0.0782	GMEB1; GMEB2 (directAnnotation).	Mono/Macro

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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."