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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
	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

Dataset: GSE164551

Dataset summary for GSE164551

Datast information	Dataset	GSE164551
	PMID	33558511
	Raw data ID/link	https://doi.org/10.7910/DVN/1RKYQ8
	Organism	Homo sapiens
	Source	patients
	Tissue	Bone marrow aspirate
	Cancer type level1	Multiple myeloma
	Cancer type level2	Refractory multiple myeloma (MM)
	Regimen	CAR-T
	Drug type	Immunotherapy
	Sample size	resistant 1, sensitive 1
	Cell number	7736
	Extract protocol	10x genomics
	Data processing	CellRanger 3.1.0
	Public date	Public on Jan 11, 2021
	Description	This dataset has 1 patient with a sensitive pre-treatment sample and a resistant post-treatment sample.

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Drug summary for GSE164551

Drug name	DrugBank ID	Drug type	Targets name	Targets uniprot ID
"CAR-T" is not included in the drug list.

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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.)

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.)

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

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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
SAMD3	ENSG00000164483	0.341297	1.46e-06	2.30e-02	0.429	0.223	NK cells	NA
ANP32A	ENSG00000140350	0.331515	2.64e-07	4.16e-03	0.42	0.191	NK cells	NA
SQSTM1	ENSG00000284099	0.317349	1.39e-06	2.19e-02	0.402	0.187	NK cells	NA
PHF1	ENSG00000225553	0.306193	5.73e-08	9.03e-04	0.25	0.074	NK cells	NA
GON4L	ENSG00000116580	0.281561	2.62e-07	4.13e-03	0.268	0.089	NK cells	NA
NDUFA13	ENSG00000186010	0.263826	3.08e-06	4.85e-02	0.295	0.121	NK cells	NA
APOBEC3G	ENSG00000239713	-0.436127	5.95e-08	9.38e-04	0.054	0.298	NK cells	NA
ITGA5	ENSG00000161638	-0.503479	1.09e-06	1.71e-02	0.045	0.254	NK cells	NA
TUBA4A	ENSG00000127824	-0.508505	3.21e-07	5.06e-03	0.089	0.328	NK cells	NA
SLC1A5	ENSG00000105281	-0.511415	5.25e-10	8.27e-06	0	0.272	NK cells	NA
LAPTM5	ENSG00000162511	-0.587828	1.39e-07	2.20e-03	0.411	0.636	NK cells	NA
GZMH	ENSG00000100450	-0.645504	9.35e-07	1.47e-02	0.188	0.427	NK cells	NA
MXD4	ENSG00000123933	-0.669622	2.38e-08	3.75e-04	0.259	0.529	NK cells	NA
LDHA	ENSG00000288299	-0.694843	1.13e-06	1.78e-02	0.259	0.463	NK cells	NA
IFRD1	ENSG00000006652	-0.704784	9.18e-09	1.45e-04	0.098	0.368	NK cells	NA
AREG	ENSG00000109321	-0.749152	3.65e-08	5.75e-04	0.152	0.421	NK cells	NA
PTMA	ENSG00000187514	-0.752743	1.34e-07	2.11e-03	0.946	0.996	NK cells	NA
VIM	ENSG00000026025	-0.779404	3.38e-12	5.33e-08	0.384	0.714	NK cells	NA
ZFP36	ENSG00000128016	-0.792631	2.33e-07	3.67e-03	0.33	0.557	NK cells	NA
IKZF1	ENSG00000185811	-0.802183	3.66e-10	5.77e-06	0.268	0.563	NK cells	NA
LGALS1	ENSG00000100097	-0.839483	3.71e-07	5.85e-03	0.214	0.469	NK cells	NA
DDIT4	ENSG00000168209	-0.850982	1.37e-09	2.15e-05	0.188	0.477	NK cells	NA
S100A6	ENSG00000197956	-0.8819	2.27e-11	3.58e-07	0.607	0.839	NK cells	NA
GRASP	NA	-0.886651	6.05e-09	9.54e-05	0.205	0.469	NK cells	NA
GZMB	ENSG00000100453	-0.926635	1.07e-07	1.69e-03	0.357	0.581	NK cells	NA
AC103591.3	NA	-0.936827	8.42e-07	1.33e-02	0.214	0.421	NK cells	NA
GZMA	ENSG00000145649	-1.02671	1.22e-08	1.92e-04	0.277	0.541	NK cells	NA
CCL4	ENSG00000277943	-1.04218	2.71e-06	4.27e-02	0.161	0.406	NK cells	NA
TMSB10	ENSG00000034510	-1.04734	1.98e-10	3.13e-06	0.955	0.992	NK cells	NA
SH3BGRL3	ENSG00000142669	-1.08374	3.14e-17	4.96e-13	0.661	0.917	NK cells	NA
S100A4	ENSG00000196154	-1.35744	4.69e-16	7.39e-12	0.589	0.875	NK cells	NA
MT1X	ENSG00000187193	2.84767	0.00e+00	0.00e+00	0.515	0.188	Mono/Macro	NA
MT2A	ENSG00000125148	2.34499	1.83e-32	2.89e-28	0.807	0.648	Mono/Macro	NA
MT1G	ENSG00000125144	1.97179	0.00e+00	0.00e+00	0.387	0.027	Mono/Macro	NA
G0S2	ENSG00000123689	1.95496	0.00e+00	0.00e+00	0.539	0.183	Mono/Macro	NA
HBB	ENSG00000244734	1.58744	0.00e+00	0.00e+00	0.911	0.526	Mono/Macro	NA
HBA2	ENSG00000188536	1.54239	0.00e+00	0.00e+00	0.907	0.466	Mono/Macro	NA
HBA1	ENSG00000206172	1.00192	3.16e-42	4.99e-38	0.673	0.387	Mono/Macro	NA
IGLC3	ENSG00000211679	0.981392	0.00e+00	0.00e+00	0.414	0.025	Mono/Macro	NA
MT1E	ENSG00000169715	0.83124	0.00e+00	0.00e+00	0.284	0.052	Mono/Macro	NA
MT-ND1	ENSG00000198888	0.79223	9.00e-34	1.42e-29	1	1	Mono/Macro	NA
MT-CYB	ENSG00000198727	0.782198	8.34e-38	1.31e-33	1	1	Mono/Macro	NA
ZNF292	ENSG00000188994	0.758491	0.00e+00	0.00e+00	0.593	0.253	Mono/Macro	NA
EGR1	ENSG00000120738	0.751089	2.43e-39	3.83e-35	0.37	0.145	Mono/Macro	NA
MT-CO3	ENSG00000198938	0.73187	1.30e-23	2.05e-19	1	1	Mono/Macro	NA
MAP3K1	ENSG00000095015	0.727307	0.00e+00	0.00e+00	0.55	0.251	Mono/Macro	NA
PTPRC	ENSG00000262418	0.709218	2.47e-43	3.88e-39	0.792	0.648	Mono/Macro	NA
MT-ND2	ENSG00000198763	0.690462	3.35e-19	5.28e-15	1	1	Mono/Macro	NA
MT-CO2	ENSG00000198712	0.664879	6.73e-21	1.06e-16	1	1	Mono/Macro	NA
YIPF4	ENSG00000119820	0.631679	0.00e+00	8.41e-45	0.483	0.21	Mono/Macro	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	5.90e-02	2.90e-01	12	781	2	23467	Malignant cells	EGR1,CXCL8
Epigenetic Alteration of DNA, RNA or Protein	2.10e-01	5.20e-01	12	455	1	23467	Malignant cells	CXCL8
Aberration of the Drug's Therapeutic Target	1.00e+00	1.00e+00	12	90	0	23467	Malignant cells
Drug Inactivation by Structure Modification	1.00e+00	1.00e+00	12	27	0	23467	Malignant cells
Irregularity in Drug Uptake and Drug Efflux	1.00e+00	1.00e+00	12	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	1.00e+00	1.00e+00	3	186	0	23467	B cells	NA
Regulation by the Disease Microenvironment	6.60e-03	6.60e-03	148	186	5	23467	CD4+ T cells	BRAF,TGFB1,SOCS3,VIM,ZEB1
Regulation by the Disease Microenvironment	1.80e-01	1.80e-01	276	186	4	23467	CD8+ T cells	NFKB1,TGFB1,CXCR4,VIM
Regulation by the Disease Microenvironment	5.10e-01	5.10e-01	467	186	4	23467	Erythrocytes	BCL2L1,MTDH,HNRNPA2B1,MALAT1
Regulation by the Disease Microenvironment	9.20e-03	9.20e-03	524	186	10	23467	Mono_Macro	BRAF,CTNNB1,TGFB1,VEGFA,ZEB2,IL1B,HNRNPA2B1,SOCS3,VIM,MALAT1
Regulation by the Disease Microenvironment	4.80e-01	4.80e-01	81	186	1	23467	NK cells	VIM

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

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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__M02848	4.05	0.193	EGR1 (inferredBy_Orthology).	CD4+ T cells
	taipale_tf_pairs__ETV5_HES7_NNCACGTGNNNNCCGGAANN_CAP	4.02	0.192	ETV5; HES7 (directAnnotation).	CD4+ T cells
	transfac_pro__M07475	3.81	0.185	TBX5 (inferredBy_Orthology).	CD4+ T cells
	cisbp__M00775	3.79	0.184	ZBTB1 (inferredBy_Orthology).	CD4+ T cells
	metacluster_84.2	3.76	0.183	RARA (directAnnotation).	CD4+ T cells
	taipale_tf_pairs__E2F1_ELK1_SGCGCNNNNNNNNNNCGGAAGN_CAP_repr	3.74	0.182	E2F1; ELK1 (directAnnotation).	CD4+ T cells
	metacluster_141.5	3.71	0.181	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).	CD4+ T cells
	jaspar__MA1650.1	3.68	0.18	ZBTB14 (directAnnotation).	CD4+ T cells
	transfac_pro__M02090	3.62	0.178	E2F4 (directAnnotation).	CD4+ T cells
	transfac_pro__M08005	3.56	0.176	TCFL5 (inferredBy_Orthology).	CD4+ T cells

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Motifs and TFs regulating down-regulated DEGs in resistant group

motif	motif	NES	AUC	TF_highConf	Cell_type
	transfac_pro__M01252	7.71	0.61	E2F6 (directAnnotation).	B cells
	tfdimers__MD00310	7.02	0.558	IKZF1; OTX1; OTX2 (directAnnotation).	B cells
	metacluster_76.1	6.65	0.53	ZNF345; ZNF345 (directAnnotation). MYB; MYBL1 (inferredBy_Orthology).	B cells
	metacluster_156.2	6.56	0.523	ATF3; ATF4; ATF4; ATF4; ATF4; ATF4; ATF4; CEBPG; CEBPG; DDIT3; MYC (directAnnotation). ATF4; ATF4; ATF4; CEBPG; DDIT3 (inferredBy_Orthology).	B cells
	transfac_pro__M05531	6.5	0.518	IKZF5 (inferredBy_Orthology).	B cells
	tfdimers__MD00103	6.44	0.514	ZNF333 (directAnnotation).	B cells
	cisbp__M00838	6.02	0.482	FOXP1 (directAnnotation).	B cells
	metacluster_130.1	5.99	0.48	ZNF713; ZNF713 (directAnnotation). HSF1; HSF2; HSF4; HSF5; HSFX1; HSFX2; HSFX3; HSFX4; HSFY1; HSFY2 (inferredBy_Orthology).	B cells
	metacluster_139.9	5.89	0.473	TFE3 (inferredBy_Orthology).	B cells
	tfdimers__MD00298	5.88	0.471	CEBPA; CEBPB; CEBPD; CEBPE; CEBPG; FOXL1 (directAnnotation).	B 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.)

TF	motif	Expression	Cell type	Timepoint
ZEB1	tfdimers__MD00527	up	CD4+ T cells	NA
MECP2	metacluster_135.10	up	CD8+ T cells	NA
E2F4	metacluster_45.6	down	Erythrocytes	NA
KLF13	hocomoco__KLF13_HUMAN.H11MO.0.D	down	Erythrocytes	NA
YBX1	metacluster_79.33	down	Erythrocytes	NA
BACH1	metacluster_22.37	up	Mono/Macro	NA
BACH1	metacluster_157.2	up	Mono/Macro	NA
BACH1	metacluster_30.4	up	Mono/Macro	NA
EGR1	cisbp__M01864	up	Mono/Macro	NA
EGR1	metacluster_131.7	up	Mono/Macro	NA

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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."
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