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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 (This dataset does not contain this module)
	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 (This dataset does not contain this module)
	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 (This dataset does not contain this module)
	Mechanism analysis of drug resistance-related DEGs for each cell type in the post-treatment samples (This dataset does not contain this module)
	Mechanism analysis of drug resistance-related DEGs for each cell type in one patient or cell lines
	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 (This dataset does not contain this module)

Dataset: GSE158457

Dataset summary for GSE158457

Datast information	Dataset	GSE158457
	PMID	34151288
	Raw data ID/link	PRJNA665257
	Organism	Homo sapiens
	Source	PDX cells
	Tissue	Cell line
	Cancer type level1	Acute lymphoblastic leukemia
	Cancer type level2	T-cell acute lymphoblastic leukemia (ALL)
	Regimen	dasatinib
	Drug type	Targeted therapy
	Sample size	resistant 2, sensitive 2
	Cell number	26026
	Extract protocol	10x genomics
	Data processing	CellRanger 3.1.0
	Public date	Public on Jan 05, 2021
	Description	The dataset has 2 patient-derived PDX cell groups, each with a sensitive pre-treatment sample and a resistant post-treatment sample.

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Drug summary for GSE158457

Drug name	DrugBank ID	Drug type	Targets name	Targets uniprot ID
"Dasatinib"	DB01254	small molecule	ABL1; SRC; EPHA2; LCK; YES1; KIT; PDGFRB; STAT5B; ABL2; FYN; BTK; NR4A3; BCR; CSK; EPHA5; EPHB4; FGR; FRK; HSPA8; LYN; ZAK; MAPK14; PPAT	P00519; P12931; P29317; P06239; P07947; P10721; P09619; P51692; P42684; P06241; Q06187; Q92570; P11274; P41240; P54756; P54760; P09769; P42685; P11142; P07948; Q9NYL2; Q16539; Q06203

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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
Umap of cell clusters	Cell ratio of drug-resistant and sensitive groups within each cluster

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Comparison of cell composition between the resistant and sensitive groups

In the pre-treatment samples, the cell composition of the resistant and sensitive groups were compared.
* represents significant difference. (If the image exists, the user can click on it to enlarge it in a new window.)

In the post-treatment samples, the cell composition of the resistant and sensitive groups were compared.
* represents significant difference. (If the image exists, the user can click on it to enlarge it in a new window.)

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

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

Comparison of ITH scores

Comparison of EMT scores

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Difference of cell-cell interactions between the resistant and sensitive groups

In the pre-treatment samples, the difference in cell-cell interactions between the resistant and sensitive groups was compared. The numbers indicate the count of cell-cell interactions that were either higher or lower in the resistant group compared to the sensitive group. The dot plots of significant ligand-receptor pairs in the resistant group and sensitive group are subsequently displayed. (If the image exists, the user can click on it to enlarge it in a new window. Complete files can be downloaded from the download section.)

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.)

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.

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.

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.

Gene symbol	Gene id	avg_log2FC	p_val	p_val_adj	pct.1	pct.2	Cell type	Timepoint
MALAT1	ENSG00000251562	0.701109	0.00e+00	0.00e+00	1	1	Malignant cells	NA
LTB	ENSG00000223448	0.697278	0.00e+00	0.00e+00	0.859	0.748	Malignant cells	NA
PTCRA	ENSG00000171611	0.595284	0.00e+00	0.00e+00	0.569	0.511	Malignant cells	NA
DNTT	ENSG00000107447	0.570476	0.00e+00	0.00e+00	0.919	0.814	Malignant cells	NA
FAM173A	NA	0.515231	0.00e+00	0.00e+00	0.883	0.794	Malignant cells	NA
MAL	ENSG00000172005	0.511008	0.00e+00	0.00e+00	0.939	0.87	Malignant cells	NA
MDM4	ENSG00000198625	0.470375	0.00e+00	0.00e+00	0.793	0.697	Malignant cells	NA
ARPP21	ENSG00000172995	0.404725	0.00e+00	0.00e+00	0.688	0.566	Malignant cells	NA
ACSF3	ENSG00000176715	0.36803	0.00e+00	0.00e+00	0.652	0.586	Malignant cells	NA
MYO7B	ENSG00000169994	0.35607	0.00e+00	0.00e+00	0.696	0.594	Malignant cells	NA
PRMT7	ENSG00000132600	0.33277	0.00e+00	0.00e+00	0.637	0.623	Malignant cells	NA
TXNIP	ENSG00000265972	0.331217	0.00e+00	0.00e+00	0.495	0.37	Malignant cells	NA
MZB1	ENSG00000170476	0.327502	0.00e+00	0.00e+00	0.95	0.918	Malignant cells	NA
BTG1	ENSG00000133639	0.318637	0.00e+00	0.00e+00	0.806	0.723	Malignant cells	NA
MED13L	ENSG00000123066	0.312461	0.00e+00	0.00e+00	0.624	0.493	Malignant cells	NA
CD3G	ENSG00000160654	0.305708	0.00e+00	0.00e+00	0.99	0.98	Malignant cells	NA
ARL4C	ENSG00000188042	0.305537	0.00e+00	0.00e+00	0.853	0.807	Malignant cells	NA
MIR181A1HG	ENSG00000229989	0.291921	0.00e+00	0.00e+00	0.606	0.479	Malignant cells	NA
TRBC1	ENSG00000281981	0.286585	0.00e+00	0.00e+00	1	0.998	Malignant cells	NA
BCL7A	ENSG00000282873	0.284763	0.00e+00	0.00e+00	0.579	0.46	Malignant cells	NA
DDX17	ENSG00000100201	0.279562	0.00e+00	0.00e+00	0.939	0.907	Malignant cells	NA
RP11-356I2.4	NA	0.272039	0.00e+00	0.00e+00	0.457	0.354	Malignant cells	NA
PNISR	ENSG00000132424	0.271818	0.00e+00	0.00e+00	0.984	0.966	Malignant cells	NA
LPAR6	ENSG00000139679	0.260741	1.04e-16	1.98e-12	0.398	0.374	Malignant cells	NA
PMEPA1	ENSG00000124225	0.259636	5.16e-42	9.81e-38	0.31	0.248	Malignant cells	NA
RP11-620J15.3	NA	0.255507	0.00e+00	0.00e+00	0.914	0.892	Malignant cells	NA
BTG2	ENSG00000159388	0.255073	0.00e+00	0.00e+00	0.476	0.351	Malignant cells	NA
HIST1H4C	NA	-0.253318	0.00e+00	2.21e-42	0.827	0.848	Malignant cells	NA
RPS20	ENSG00000008988	-0.255941	0.00e+00	0.00e+00	0.941	0.976	Malignant cells	NA
DHFR	ENSG00000228716	-0.257431	0.00e+00	0.00e+00	0.25	0.391	Malignant cells	NA
KRT1	ENSG00000167768	-0.257526	0.00e+00	0.00e+00	0.292	0.395	Malignant cells	NA
RPL23A	ENSG00000198242	-0.257742	0.00e+00	0.00e+00	1	1	Malignant cells	NA
MCM7	ENSG00000166508	-0.258101	0.00e+00	0.00e+00	0.347	0.471	Malignant cells	NA
HNRNPU	ENSG00000153187	-0.258712	0.00e+00	0.00e+00	0.719	0.818	Malignant cells	NA
DNMT1	ENSG00000130816	-0.259064	0.00e+00	0.00e+00	0.404	0.527	Malignant cells	NA
TMEM106C	ENSG00000134291	-0.259258	0.00e+00	0.00e+00	0.23	0.354	Malignant cells	NA
SKAP1	ENSG00000141293	-0.259925	0.00e+00	0.00e+00	0.125	0.27	Malignant cells	NA
KIF11	ENSG00000138160	-0.260173	0.00e+00	0.00e+00	0.145	0.267	Malignant cells	NA
TMSB4X	ENSG00000205542	-0.260382	0.00e+00	0.00e+00	1	1	Malignant cells	NA
SLBP	ENSG00000163950	-0.261767	0.00e+00	0.00e+00	0.331	0.447	Malignant cells	NA
ATAD2	ENSG00000156802	-0.263056	0.00e+00	0.00e+00	0.244	0.385	Malignant cells	NA
SRSF2	ENSG00000161547	-0.264792	0.00e+00	0.00e+00	0.69	0.786	Malignant cells	NA
ALYREF	ENSG00000183684	-0.266553	0.00e+00	0.00e+00	0.297	0.433	Malignant cells	NA
FBXO5	ENSG00000112029	-0.268491	0.00e+00	0.00e+00	0.166	0.292	Malignant cells	NA
MCM3	ENSG00000112118	-0.268554	0.00e+00	0.00e+00	0.284	0.405	Malignant cells	NA
NPM1	ENSG00000181163	-0.269223	0.00e+00	0.00e+00	0.989	0.995	Malignant cells	NA
PSIP1	ENSG00000164985	-0.269556	0.00e+00	0.00e+00	0.608	0.683	Malignant cells	NA
ZWINT	ENSG00000122952	-0.269697	0.00e+00	0.00e+00	0.206	0.349	Malignant cells	NA
VDAC1	ENSG00000213585	-0.270959	0.00e+00	0.00e+00	0.392	0.556	Malignant cells	NA
RPS2	ENSG00000140988	-0.271162	0.00e+00	0.00e+00	1	1	Malignant cells	NA

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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.)

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.)

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.)

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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.)

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.)

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.)

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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.)

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	5.20e-14	2.60e-13	146	781	28	23467	Malignant cells	BIRC5,DNMT1,HMGA1,HMGB1,PKM,RPS6,STMN1,TYMS,ANXA1,BTG1,CDK1,DHFR,GAPDH,HMGB2,HNRNPU,KIF11,LDHA,MDM4,NUCKS1,PGK1,RRM1,RRM2,SMC4,SRSF2,UBE2C,YBX1,ENO1,NPM1
Aberration of the Drug's Therapeutic Target	1.90e-02	4.70e-02	146	90	3	23467	Malignant cells	DHFR,NPM1,TOP2A
Epigenetic Alteration of DNA, RNA or Protein	1.50e-01	2.60e-01	146	455	5	23467	Malignant cells	DNMT1,TYMS,GAPDH,SMC4,MALAT1
Drug Inactivation by Structure Modification	1.00e+00	1.00e+00	146	27	0	23467	Malignant cells
Irregularity in Drug Uptake and Drug Efflux	1.00e+00	1.00e+00	146	37	0	23467	Malignant cells

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.)

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

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.)

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

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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.)

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.)

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.)

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

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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.)

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.)

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.)

Motifs and TFs regulating up-regulated DEGs in resistant group

motif	motif	NES	AUC	TF_highConf	Cell_type
	transfac_pro__M02108	5.05	0.188	NKX2-5 (directAnnotation).	Malignant cells
	metacluster_160.5	4.39	0.168	ZNF189; ZNF189; ZNF341 (directAnnotation).	Malignant cells
	hdpi__VAX2	4.3	0.166	VAX2 (directAnnotation).	Malignant cells
	metacluster_141.4	4.29	0.165	GLIS2 (directAnnotation).	Malignant cells
	metacluster_135.3	4.12	0.16	ZNF486 (directAnnotation).	Malignant cells
	metacluster_19.1	4.01	0.157	GMEB2; GMEB2; GMEB2 (directAnnotation).	Malignant cells
	hocomoco__TYY2_HUMAN.H11MO.0.D	4.01	0.157	YY2 (directAnnotation).	Malignant cells
	transfac_pro__M04843	4	0.157	SMC3 (directAnnotation).	Malignant cells
	swissregulon__hs__SMAD3	4	0.157	SMAD3 (directAnnotation).	Malignant cells
	transfac_pro__M06160	3.84	0.152	ZNF92 (directAnnotation).	Malignant cells

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Motifs and TFs regulating down-regulated DEGs in resistant group

motif	motif	NES	AUC	TF_highConf	Cell_type
	metacluster_174.2	8.01	0.128	CEBPZ; CEBPZ; DRAP1; FOS; FOXI1; FOXI1; HMGXB3; IRF3; NFYA; NFYA; NFYA; NFYA; NFYA; NFYA; NFYA; NFYA; NFYA; NFYB; NFYB; NFYB; NFYB; NFYB; NFYC; NFYC; NFYC; NFYC; NFYC; NFYC; NFYC; PBX3; PBX3; SP2 (directAnnotation). NFYA; NFYA; NFYC; PBX1; PBX3 (inferredBy_Orthology).	Malignant cells
	metacluster_174.3	7.79	0.125	MBD2; NFYA; NFYB; NFYC; PBX3 (directAnnotation).	Malignant cells
	metacluster_174.6	7.75	0.125	NFYA; NFYB; NFYB; NFYC (directAnnotation).	Malignant cells
	swissregulon__mm__E2f7	5.56	0.0968	E2F7 (inferredBy_Orthology).	Malignant cells
	metacluster_45.6	5.17	0.0918	E2F1; E2F1; E2F1; E2F1; E2F1; E2F2; E2F2; E2F2; E2F3; E2F3; E2F3; E2F4; E2F4 (directAnnotation). E2F2; E2F3 (inferredBy_Orthology).	Malignant cells
	metacluster_102.2	5.14	0.0914	ZBED1 (directAnnotation).	Malignant cells
	transfac_pro__M06894	4.73	0.0862	ZFP90 (inferredBy_Orthology).	Malignant cells
	transfac_pro__M05474	4.6	0.0845	ZNF639 (directAnnotation).	Malignant cells
	cisbp__M00808	4.59	0.0843	MYPOP (inferredBy_Orthology).	Malignant cells
	metacluster_141.2	4.49	0.0831	E2F2; E2F3 (directAnnotation).	Malignant cells

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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.)

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."