Home

Download

Statistics

Landscape

Help

Contact

	Dataset summary
	Drug summary
	Umap of single cell types and conditions (resistant and sensitive)
	Comparison of cell composition between the resistant and sensitive groups
	Comparison of intra-tumor heterogeneity (ITH) and epithelial-mesenchymal transition (EMT) scores of malignant cells between the resistant and sensitive groups
	Difference of cell-cell interactions between the resistant and sensitive groups
	Differentially expressed genes (DEGs) between the resistant and sensitive groups for each cell type
	Mechanism analysis of drug resistance-related DEGs for each cell type in the pre-treatment samples
	Mechanism analysis of drug resistance-related DEGs for each cell type in the post-treatment samples
	Mechanism analysis of drug resistance-related DEGs for each cell type in one patient or cell lines (This dataset does not contain this module)
	MicroRNAs (miRNAs) regulating drug resistance-related DEGs for Malignant cells
	Motifs and transcription factors (TFs) regulating drug resistance-related DEGs for each cell type
•	Differentially expressed genes act as transcription factors

Dataset: GSE199333

Dataset summary for GSE199333

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

Top

Drug summary for GSE199333

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

Top

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

Top

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.)

Top

Comparison of ITH and EMT scores of malignant cells between the resistant and sensitive groups

Comparison of ITH (intra-tumoral heterogeneity) and EMT (epithelial-mesenchymal transition) scores of malignant cells between the resistant and sensitive groups. ITH represents intratumoral heterogeneity, EMT represents epithelial mesenchymal transition, pre represents pre-treatment, post represents post-treatment, post2 represents longer post-treatment. (If the image exists, the user can click on it to enlarge it in a new window.)

Comparison of ITH scores

Comparison of EMT scores

Top

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.)

Top

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
PLEC	ENSG00000178209	-0.476852	0.00e+00	0.00e+00	0.042	0.278	Malignant cells	pre
SEC61B	ENSG00000106803	-0.478675	0.00e+00	0.00e+00	0.781	0.912	Malignant cells	pre
COMMD3	ENSG00000148444	-0.479245	0.00e+00	0.00e+00	0.266	0.495	Malignant cells	pre
ACTR2	ENSG00000138071	-0.480352	0.00e+00	0.00e+00	0.589	0.822	Malignant cells	pre
PBX3	ENSG00000167081	-0.48302	0.00e+00	0.00e+00	0.199	0.491	Malignant cells	pre
PTPN7	ENSG00000143851	-0.484284	0.00e+00	0.00e+00	0.303	0.528	Malignant cells	pre
CTNNB1	ENSG00000168036	-0.484839	0.00e+00	0.00e+00	0.491	0.623	Malignant cells	pre
ATP2B1-AS1	ENSG00000271614	-0.484934	0.00e+00	0.00e+00	0.168	0.335	Malignant cells	pre
SYNCRIP	ENSG00000135316	-0.487697	0.00e+00	0.00e+00	0.375	0.641	Malignant cells	pre
CDKN2D	ENSG00000129355	-0.489936	0.00e+00	0.00e+00	0.156	0.395	Malignant cells	pre
KLF6	ENSG00000067082	-0.492278	0.00e+00	0.00e+00	0.71	0.769	Malignant cells	pre
HEBP2	ENSG00000051620	-0.494735	0.00e+00	0.00e+00	0.533	0.737	Malignant cells	pre
KDM6B	ENSG00000132510	-0.495995	0.00e+00	0.00e+00	0.136	0.349	Malignant cells	pre
NDUFV2	ENSG00000178127	-0.497957	0.00e+00	0.00e+00	0.388	0.678	Malignant cells	pre
CAP1	ENSG00000131236	-0.498607	0.00e+00	0.00e+00	0.419	0.721	Malignant cells	pre
PRELID1	ENSG00000169230	-0.503167	0.00e+00	0.00e+00	0.533	0.758	Malignant cells	pre
YWHAB	ENSG00000166913	-0.506584	0.00e+00	0.00e+00	0.576	0.823	Malignant cells	pre
MBNL1	ENSG00000152601	-0.506724	0.00e+00	0.00e+00	0.573	0.739	Malignant cells	pre
HSPD1	ENSG00000144381	-0.507417	0.00e+00	0.00e+00	0.507	0.634	Malignant cells	pre
TNIP1	ENSG00000145901	-0.510155	0.00e+00	0.00e+00	0.247	0.45	Malignant cells	pre
BAHCC1	ENSG00000266074	-0.510506	0.00e+00	0.00e+00	0.237	0.515	Malignant cells	pre
SPN	ENSG00000197471	-0.511917	0.00e+00	0.00e+00	0.553	0.759	Malignant cells	pre
RGCC	ENSG00000102760	-0.512918	0.00e+00	0.00e+00	0.135	0.323	Malignant cells	pre
MT-CO3	ENSG00000198938	-0.513389	0.00e+00	0.00e+00	1	1	Malignant cells	pre
SQSTM1	ENSG00000284099	-0.517592	0.00e+00	0.00e+00	0.434	0.632	Malignant cells	pre
AHR	ENSG00000106546	-0.518284	0.00e+00	0.00e+00	0.169	0.438	Malignant cells	pre
NFKB2	ENSG00000077150	-0.524806	0.00e+00	0.00e+00	0.06	0.295	Malignant cells	pre
GATA2	ENSG00000179348	-0.525415	0.00e+00	0.00e+00	0.149	0.364	Malignant cells	pre
TRGC2	ENSG00000227191	-0.525728	0.00e+00	0.00e+00	0.082	0.365	Malignant cells	pre
ATP2B1	ENSG00000070961	-0.526201	0.00e+00	0.00e+00	0.263	0.501	Malignant cells	pre
SOCS2	ENSG00000120833	-0.527831	0.00e+00	0.00e+00	0.209	0.42	Malignant cells	pre
P4HB	ENSG00000185624	-0.528555	0.00e+00	0.00e+00	0.542	0.699	Malignant cells	pre
HOXB3	ENSG00000120093	-0.530017	0.00e+00	0.00e+00	0.114	0.429	Malignant cells	pre
COTL1	ENSG00000103187	-0.530098	0.00e+00	0.00e+00	0.422	0.521	Malignant cells	pre
HOXA9	ENSG00000078399	-0.53082	0.00e+00	0.00e+00	0.249	0.561	Malignant cells	pre
PPA1	ENSG00000180817	-0.532622	0.00e+00	0.00e+00	0.549	0.777	Malignant cells	pre
AC103591.3	NA	-0.533184	0.00e+00	0.00e+00	0.195	0.455	Malignant cells	pre
HIST1H1D	NA	-0.534385	0.00e+00	0.00e+00	0.167	0.295	Malignant cells	pre
TRIM8	ENSG00000171206	-0.538267	0.00e+00	0.00e+00	0.342	0.577	Malignant cells	pre
CMTM6	ENSG00000091317	-0.541003	0.00e+00	0.00e+00	0.429	0.656	Malignant cells	pre
OSBPL8	ENSG00000091039	-0.542212	0.00e+00	0.00e+00	0.25	0.552	Malignant cells	pre
DDIT4	ENSG00000168209	-0.545203	0.00e+00	0.00e+00	0.105	0.32	Malignant cells	pre
TYMS	ENSG00000176890	-0.54761	0.00e+00	0.00e+00	0.106	0.251	Malignant cells	pre
PFN1	ENSG00000108518	-0.547975	0.00e+00	0.00e+00	0.941	0.976	Malignant cells	pre
RAB34	ENSG00000109113	-0.548411	0.00e+00	0.00e+00	0.112	0.513	Malignant cells	pre
CCND3	ENSG00000112576	-0.548778	0.00e+00	0.00e+00	0.165	0.468	Malignant cells	pre
SMAD3	ENSG00000166949	-0.549351	0.00e+00	0.00e+00	0.034	0.291	Malignant cells	pre
VSIR	ENSG00000107738	-0.550532	0.00e+00	0.00e+00	0.206	0.512	Malignant cells	pre
YWHAZ	ENSG00000164924	-0.555218	0.00e+00	0.00e+00	0.697	0.868	Malignant cells	pre
JUN	ENSG00000177606	-0.555661	0.00e+00	0.00e+00	0.383	0.533	Malignant cells	pre

Page: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49

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
IL32	ENSG00000008517	2.17	0.00e+00	0.00e+00	0.932	0.485	NK cells	post
S100B	ENSG00000160307	1.97467	0.00e+00	0.00e+00	0.361	0.076	NK cells	post
HBA2	ENSG00000188536	1.88758	0.00e+00	0.00e+00	0.986	0.72	NK cells	post
CD52	ENSG00000169442	1.79886	0.00e+00	0.00e+00	0.97	0.609	NK cells	post
HBG2	ENSG00000196565	1.66961	0.00e+00	0.00e+00	0.559	0.021	NK cells	post
S100A4	ENSG00000196154	1.65955	0.00e+00	0.00e+00	0.997	0.918	NK cells	post
CD3D	ENSG00000167286	1.56678	0.00e+00	0.00e+00	0.701	0.195	NK cells	post
HBA1	ENSG00000206172	1.56425	0.00e+00	0.00e+00	0.944	0.625	NK cells	post
HBB	ENSG00000244734	1.52301	0.00e+00	0.00e+00	0.997	0.798	NK cells	post
CD3G	ENSG00000160654	1.41661	0.00e+00	0.00e+00	0.634	0.147	NK cells	post
TRDC	ENSG00000211829	1.41284	0.00e+00	0.00e+00	0.597	0.34	NK cells	post
TRGC1	ENSG00000211689	1.40926	0.00e+00	0.00e+00	0.488	0.11	NK cells	post
LTB	ENSG00000223448	1.35923	0.00e+00	0.00e+00	0.413	0.153	NK cells	post
UCP2	ENSG00000175567	1.22223	0.00e+00	0.00e+00	0.694	0.21	NK cells	post
S100A11	ENSG00000163191	1.21366	0.00e+00	0.00e+00	0.621	0.141	NK cells	post
KLRC1	ENSG00000134545	1.1889	0.00e+00	0.00e+00	0.578	0.243	NK cells	post
EMP3	ENSG00000142227	1.18878	0.00e+00	0.00e+00	0.91	0.59	NK cells	post
MYL12A	ENSG00000101608	1.17951	0.00e+00	0.00e+00	0.965	0.785	NK cells	post
PRF1	ENSG00000180644	1.17922	0.00e+00	0.00e+00	0.854	0.624	NK cells	post
CLIC1	ENSG00000226651	1.1724	0.00e+00	0.00e+00	0.906	0.569	NK cells	post
ANXA1	ENSG00000135046	1.13565	0.00e+00	0.00e+00	0.925	0.573	NK cells	post
MT-ND5	ENSG00000198786	1.06264	0.00e+00	0.00e+00	1	0.991	NK cells	post
KLRG1	ENSG00000139187	1.04741	0.00e+00	0.00e+00	0.522	0.12	NK cells	post
LGALS1	ENSG00000100097	1.03936	0.00e+00	0.00e+00	0.818	0.612	NK cells	post
TRAC	ENSG00000277734	1.0277	0.00e+00	0.00e+00	0.453	0.143	NK cells	post
TRGC2	ENSG00000227191	1.01901	0.00e+00	0.00e+00	0.453	0.074	NK cells	post
S100A10	ENSG00000197747	1.01435	0.00e+00	0.00e+00	0.857	0.587	NK cells	post
VIM	ENSG00000026025	1.01225	0.00e+00	0.00e+00	0.945	0.666	NK cells	post
MYL12B	ENSG00000118680	1.00573	0.00e+00	0.00e+00	0.938	0.66	NK cells	post
RAC2	ENSG00000128340	0.981839	0.00e+00	0.00e+00	0.84	0.508	NK cells	post
PTPRC	ENSG00000262418	0.979755	0.00e+00	0.00e+00	0.96	0.787	NK cells	post
LCK	ENSG00000182866	0.962841	0.00e+00	0.00e+00	0.669	0.255	NK cells	post
APOBEC3G	ENSG00000239713	0.955681	0.00e+00	0.00e+00	0.639	0.225	NK cells	post
ARPC1B	ENSG00000130429	0.946425	0.00e+00	0.00e+00	0.736	0.366	NK cells	post
TMSB4X	ENSG00000205542	0.919034	0.00e+00	0.00e+00	1	1	NK cells	post
GZMA	ENSG00000145649	0.910422	0.00e+00	0.00e+00	0.96	0.837	NK cells	post
OAZ1	ENSG00000104904	0.908407	0.00e+00	0.00e+00	0.94	0.705	NK cells	post
CORO1A	ENSG00000102879	0.898535	0.00e+00	0.00e+00	0.904	0.686	NK cells	post
MYOM2	ENSG00000274137	0.896284	0.00e+00	0.00e+00	0.33	0.076	NK cells	post
SH3BGRL3	ENSG00000142669	0.892297	0.00e+00	0.00e+00	0.999	0.983	NK cells	post
ANXA6	ENSG00000197043	0.884231	0.00e+00	0.00e+00	0.619	0.244	NK cells	post
PSMB9	ENSG00000239836	0.877848	0.00e+00	0.00e+00	0.685	0.31	NK cells	post
GZMK	ENSG00000113088	0.875706	4.68e-19	9.94e-15	0.262	0.184	NK cells	post
TRBC1	ENSG00000281981	0.859215	0.00e+00	0.00e+00	0.603	0.35	NK cells	post
RIPOR2	ENSG00000111913	0.854837	0.00e+00	0.00e+00	0.613	0.26	NK cells	post
ARPC5	ENSG00000162704	0.830901	0.00e+00	0.00e+00	0.569	0.202	NK cells	post
EVL	ENSG00000196405	0.825301	0.00e+00	0.00e+00	0.819	0.568	NK cells	post
ANXA2	ENSG00000182718	0.802407	0.00e+00	0.00e+00	0.561	0.219	NK cells	post
PRMT2	ENSG00000160310	0.793528	0.00e+00	0.00e+00	0.657	0.398	NK cells	post
CD53	ENSG00000143119	0.787895	0.00e+00	0.00e+00	0.683	0.389	NK cells	post

Page: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106

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.

Top

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

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

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

Mechnism	Pval	FDR	Signature	Geneset	Overlap	Background	Cell type	Enriched Genes
Unusual Activation of Pro-survival Pathway	2.10e-24	1.10e-23	848	781	93	23467	Malignant cells	ANXA2,AREG,BCL11A,BRAF,CCND2,CTNNB1,DNMT1,DUSP6,GSTP1,HIF1A,HMGA1,HOXB3,EIF4G1,JUN,PKM,MEF2D,NFKB1,PARP1,KRAS,RHOA,S100A4,SELENOW,SOCS2,STMN1,TYMS,ZEB2,YWHAZ,SLC25A5,ANXA1,BID,BRD4,CD44,HSPD1,CLTC,CLU,CYLD,DDIT3,DUSP1,EIF3A,HSP90B1,EZR,FLT3,GRB2,HNRNPU,HSPA8,HSPB1,HOXA5,NFKBIA,CXCL8,ITGA5,TCF4,LASP1,LDHA,LRRFIP1,MTDH,MAP3K1,MAP3K8,NCOA3,NUCKS1,PABPC1,POMP,PRKDC,PTPN1,RAB14,RAC1,RAP1A,RAP1B,RASSF1,RICTOR,RSF1,S100A11,SFPQ,SMAD3,SMC4,RBPJ,YY1,UCP2,ZBTB7A,ENO1,GNAS,CALR,CSF3R,GNAQ,EIF4EBP1,IL2RA,MDK,REL,RELB,QPRT,ACAP2,TNFAIP8,UBR5,HSH2D
Drug Inactivation by Structure Modification	6.30e-01	1.00e+00	848	27	1	23467	Malignant cells	GSTP1
Aberration of the Drug's Therapeutic Target	8.40e-01	1.00e+00	848	90	2	23467	Malignant cells	BRAF,FLT3
Epigenetic Alteration of DNA, RNA or Protein	9.40e-01	1.00e+00	848	455	11	23467	Malignant cells	BRAF,DNMT1,LMNA,TYMS,CXCL8,MAP3K8,RASSF1,SMC4,TIMP1,MALAT1,GDI2
Irregularity in Drug Uptake and Drug Efflux	1.00e+00	1.00e+00	848	37	0	23467	Malignant cells

Enrichment results for 1 known drug resistance mechanisms in TME cells

Mechnism	Pval	FDR	Signature	Geneset	Overlap	Background	Cell type	Enriched Genes
Regulation by the Disease Microenvironment	3.70e-01	3.70e-01	504	186	5	23467	B cells	PARP1,ZEB2,HNRNPA2B1,LDHB,MALAT1
Regulation by the Disease Microenvironment	3.40e-01	3.40e-01	151	186	2	23467	CD4+ T cells	CXCR4,SOCS3
Regulation by the Disease Microenvironment	9.70e-01	9.70e-01	447	186	1	23467	CD8+ T cells	CXCR4
Regulation by the Disease Microenvironment	9.10e-01	9.10e-01	295	186	1	23467	Erythrocytes	LDHB
Regulation by the Disease Microenvironment	3.60e-01	3.60e-01	158	186	2	23467	NK cells	CXCR4,VIM

Hallmark, KEGG and GOBP enrichment results for up-regulated genes in resistant group of pre-treatment samples. Only show the top 50 pathways with fdr<0.05. If certain cell types are not displayed, it means that there are no significant pathways based on DEGs in those cell types. (If the image exists, the user can click on it to enlarge it in a new window. Complete files can be downloaded from the download section.)

Up-regulated Hallmark	Up-regulated KEGG	Up-regulated GO BP

Hallmark, KEGG and GOBP enrichment results for down-regulated genes in resistant group of pre-treatment samples. Only show the top 50 pathways with fdr<0.05. If certain cell types are not displayed, it means that there are no significant pathways based on DEGs in those cell types. (If the image exists, the user can click on it to enlarge it in a new window.Complete files can be downloaded from the download section.)

Down-regulated Hallmark	Down-regulated KEGG	Down-regulated GO BP

Top

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

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

Enrichment results for 5 known drug resistance mechanisms in malignant cells

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

Enrichment results for 1 known drug resistance mechanisms in TME cells

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

Hallmark, KEGG and GOBP enrichment results for up-regulated genes in resistant group of post-treatment samples. Only show the top 50 pathways with fdr<0.05. If certain cell types are not displayed, it means that there are no significant pathways based on DEGs in those cell types. (If the image exists, the user can click on it to enlarge it in a new window. Complete files can be downloaded from the download section.)

Up-regulated Hallmark	Up-regulated KEGG	Up-regulated GO BP

Hallmark, KEGG and GOBP enrichment results for down-regulated genes in resistant group of post-treatment samples. Only show the top 50 pathways with fdr<0.05. If certain cell types are not displayed, it means that there are no significant pathways based on DEGs in those cell types. (If the image exists, the user can click on it to enlarge it in a new window. Complete files can be downloaded from the download section.)

Down-regulated Hallmark	Down-regulated KEGG	Down-regulated GO BP

Top

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.)

Top

MicroRNAs (miRNAs) regulating drug resistance-related DEGs for malignant cells

In the pre-treatment samples, the miRNAs with a score greater than 80 that regulate the top10 abs(avg_log2FC) drug resistance-related DEGs for malignant cells are shown here. If the gene does not have any miRNAs with a score greater than 80, it will not be shown. Here only the names of miRNAs with a score greater than 90 are shown, but some names will not be shown because of too many overlaps. (Complete files containing all datasets and cell types can be downloaded from the download section.)

Regulating up-regulated DEGs in resistant group	Regulating down-regulated DEGs in resistant group

In the post-treatment samples, the miRNAs with a score greater than 80 that regulate the top10 abs(avg_log2FC) drug resistance-related DEGs for Malignant cells are shown here. If the gene does not have any miRNAs with a score greater than 80, it will not be shown. Here only the names of miRNAs with a score greater than 90 are shown, but some names will not be shown because of too many overlaps. (Complete files containing all datasets and cell types can be downloaded from the download section.)

Regulating up-regulated DEGs in resistant group	Regulating down-regulated DEGs in resistant group

This dataset only has one patient or is a cell line dataset, the resistant sample is the post-treatment sample and the sensitive sample is the pre-treatment sample. The miRNAs with a score greater than 80 that regulate the top10 abs(avg_log2FC) drug resistance-related DEGs for Malignant cells are shown here. Here only the names of miRNAs with a score greater than 80 are shown, but some names will not be shown because of too many overlaps. If the gene does not have any miRNAs with a score greater than 90, it will not be shown. (Complete files containing all datasets and cell types can be downloaded from the download section.)

Top

Motifs and transcription factors (TFs) regulating drug resistance-related DEGs for each cell type

In the pre-treatment samples, the motifs and TFs that regulate drug resistance-related DEGs for each cell type are shown here. (Complete files can be downloaded from the download section.)

Motifs and TFs regulating up-regulated DEGs in resistant group of the pre-treatment samples

motif	motif	NES	AUC	TF_highConf	Cell_type
	taipale_tf_pairs__TEAD4_ELK1_RGAATSCGGAAGYN_CAP_repr	5.13	0.115	ELK1; TEAD4 (directAnnotation).	B cells
	transfac_pro__M06847	4.84	0.109	SALL3 (inferredBy_Orthology).	B cells
	transfac_pro__M05441	4.73	0.107	ZNF396 (directAnnotation).	B cells
	metacluster_10.48	4.5	0.103	ID2 (inferredBy_Orthology).	B cells
	transfac_pro__M05605	4.46	0.102	GATA6 (inferredBy_Orthology).	B cells
	transfac_pro__M04862	4.39	0.101	NRF1 (directAnnotation).	B cells
	flyfactorsurvey__Max_Mnt_SANGER_5_FBgn0017578	4.37	0.101	MAX (inferredBy_Orthology).	B cells
	taipale_tf_pairs__ERF_FOXI1_RSCGGATGTTKWN_CAP_repr	4.31	0.0997	ERF; FOXI1 (directAnnotation).	B cells
	transfac_pro__M06794	4.31	0.0996	ZNF107 (directAnnotation).	B cells
	metacluster_14.8	4.26	0.0987	MLX (directAnnotation).	B cells

Page: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

Motifs and TFs regulating down-regulated DEGs in resistant group of the pre-treatment samples

motif	motif	NES	AUC	TF_highConf	Cell_type
	hocomoco__TYY2_HUMAN.H11MO.0.D	7.1	0.0808	YY2 (directAnnotation).	B cells
	metacluster_141.4	6.13	0.0734	GLIS2 (directAnnotation).	B cells
	taipale__YY2_DBD_NNCCGCCATNW_repr	5.96	0.072	YY2 (directAnnotation).	B cells
	metacluster_141.2	5.65	0.0696	E2F2; E2F3 (directAnnotation).	B cells
	hdpi__TP73	5.5	0.0685	TP73 (directAnnotation).	B cells
	flyfactorsurvey__pho_SOLEXA_F1-3	5.49	0.0684	YY1 (inferredBy_Orthology).	B cells
	metacluster_166.4	5.03	0.0649	BCLAF1; EHF; ELF1; ELF1; ELF1; ELF1; ELF1; ELF1; ELF2; ELF2; ELF4; ELK1; ELK1; ELK1; ELK1; ELK1; ELK1; ELK1; ELK1; ELK1; ELK3; ELK3; ELK3; ELK3; ELK4; ERG; ERG; ERG; ERG; ETS1; ETS1; ETS1; ETS1; ETS1; ETV1; ETV1; ETV1; ETV1; ETV2; ETV3; ETV4; ETV4; ETV4; ETV4; ETV4; ETV5; ETV7; FEV; FEV; FLI1; FLI1; FLI1; FLI1; GABPA; GABPA; GABPA; GABPA; GABPA; GABPA; GABPB1; GATAD1; PHF20; ZBTB25; ZBTB40 (directAnnotation). EHF; ELF1; ELF1; ELF3; ELF5; ELK3; ELK4; ERG; ETS1; ETV1; ETV2; ETV4; FLI1; GABPA; GABPA (inferredBy_Orthology).	B cells
	jaspar__MA1483.2	4.99	0.0646	ELF2 (directAnnotation).	B cells
	taipale_tf_pairs__ETS2_RCCGGAAGTG_HT	4.89	0.0638	ETS2 (directAnnotation).	B cells
	metacluster_172.6	4.77	0.0629	CHD2; E2F1 (directAnnotation).	B cells

Page: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

In the post-treatment samples, the motifs and TFs that regulate drug resistance-related DEGs for each cell type are shown here. (Complete files can be downloaded from the download section.)

Motifs and TFs regulating up-regulated DEGs in resistant group of the post-treatment samples

motif	motif	NES	AUC	TF_highConf	Cell_type
	hdpi__FLI1	6.39	0.105	FLI1 (directAnnotation).	B cells
	taipale_tf_pairs__ELF2_NATGCGGAAGTR_HT	6.18	0.102	ELF2 (directAnnotation).	B cells
	taipale_tf_pairs__ETS2_RCCGGAAGTG_HT	6	0.1	ETS2 (directAnnotation).	B cells
	jaspar__MA1708.1	5.94	0.0991	ETV7 (directAnnotation).	B cells
	taipale_tf_pairs__ETV5_HOXA2_RSCGGWAATKR_CAP	5.64	0.0952	ETV5; HOXA2 (directAnnotation).	B cells
	taipale_tf_pairs__TEAD4_ETV1_RSCGGAAATRCM_CAP	5.49	0.0933	ETV1; TEAD4 (directAnnotation).	B cells
	jaspar__MA1483.2	5.17	0.0892	ELF2 (directAnnotation).	B cells
	taipale_tf_pairs__TEAD4_ERG_RSCGGAAATRCC_CAP	5.04	0.0874	ERG; TEAD4 (directAnnotation).	B cells
	taipale_tf_pairs__HOXB2_ETV1_ACCGGAAATGA_CAP	4.78	0.084	ETV1; HOXB2 (directAnnotation).	B cells
	taipale_tf_pairs__TEAD4_ERG_RSCGGAAATRCC_CAP_repr	4.73	0.0834	ERG; TEAD4 (directAnnotation).	B cells

Page: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Motifs and TFs regulating down-regulated DEGs in resistant group of the post-treatment samples

motif	motif	NES	AUC	TF_highConf	Cell_type
	transfac_pro__M12602	6.17	0.446	ESR1 (directAnnotation).	B cells
	transfac_pro__M04960	6.02	0.436	POU5F1 (directAnnotation).	B cells
	tfdimers__MD00234	5.91	0.428	CDX2; TFAP2C (directAnnotation).	B cells
	tfdimers__MD00426	5.85	0.425	GFI1; GFI1B; SMAD4 (directAnnotation).	B cells
	taipale_tf_pairs__GCM1_ELF1_NRCCCRNNCGGAAGNN_CAP_repr	5.43	0.396	ELF1; GCM1 (directAnnotation).	B cells
	tfdimers__MD00481	5.22	0.382	MZF1; OVOL2 (directAnnotation).	B cells
	transfac_pro__M06194	5.22	0.382	ZNF121 (directAnnotation).	B cells
	transfac_pro__M08903	5.2	0.381	TEAD3 (directAnnotation).	B cells
	tfdimers__MD00214	5.15	0.377	CRX (directAnnotation).	B cells
	hocomoco__MXI1_MOUSE.H11MO.1.A	5.05	0.371	MXI1 (inferredBy_Orthology).	B cells

Page: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35

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.)

Top

Differentially expressed genes act as transcription factors

This table shows the differentially expressed genes that act as transcription factors. (Complete files can be downloaded from the download section.)

TF	motif	Expression	Cell type	Timepoint
ETS1	metacluster_138.2	up	CD4+ T cells	post
ETS1	metacluster_166.4	up	CD4+ T cells	post
ETS1	metacluster_191.3	up	CD4+ T cells	post
ELF1	metacluster_138.2	down	CD4+ T cells	post
BCLAF1	metacluster_166.4	down	CD4+ T cells	post
ELF1	metacluster_166.4	down	CD4+ T cells	post
ELF1	taipale_tf_pairs__HOXB2_ELF1_NNYMATTANNNNNNNGGAAGNN_CAP_repr	down	CD4+ T cells	post
ELF1	metacluster_191.3	down	CD4+ T cells	post
JUN	metacluster_157.2	up	CD8+ T cells	post
JUNB	metacluster_157.2	up	CD8+ T cells	post

Page: 1 2 3

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."