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Center for Computational Systems Medicine
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Dataset summary

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Drug summary

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Umap of single cell types and conditions (resistant and sensitive)

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Comparison of cell composition between the resistant and sensitive groups (This dataset does not contain this module)

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Comparison of intra-tumor heterogeneity (ITH) and epithelial-mesenchymal transition (EMT) scores of malignant cells between the resistant and sensitive groups

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

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Differentially expressed genes (DEGs) 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 (This dataset does not contain this module)

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

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Mechanism analysis of drug resistance-related DEGs for each cell type in one patient or cell lines

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

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

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Differentially expressed genes act as transcription factors

Dataset: GSE164551

Dataset summary for GSE164551

Datast informationDatasetGSE164551
PMID33558511
Raw data ID/linkhttps://doi.org/10.7910/DVN/1RKYQ8
OrganismHomo sapiens
Sourcepatients
TissueBone marrow aspirate
Cancer type level1Multiple myeloma
Cancer type level2Refractory multiple myeloma (MM)
RegimenCAR-T
Drug typeImmunotherapy
Sample sizeresistant 1, sensitive 1
Cell number7736
Extract protocol10x genomics
Data processingCellRanger 3.1.0
Public datePublic on Jan 11, 2021
DescriptionThis 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 nameDrugBank IDDrug typeTargets nameTargets 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)

check buttonUmap 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 typesboxplotUmap of conditionsboxplot

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Comparison of cell composition between the resistant and sensitive groups

check buttonIn 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.)

check buttonIn 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

check buttonComparison 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 scoresboxplotComparison of EMT scoresboxplot

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

check buttonIn 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.)

check buttonIn 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.)

check buttonThis 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

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Dot plot of significant ligand-receptor pairs in the resistant groupDot 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

check buttonIn 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.

check buttonIn 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.

check buttonThis 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 symbolGene idavg_log2FCp_valp_val_adjpct.1pct.2Cell typeTimepoint

GLIPR1

ENSG00000139278-0.3050281.39e-152.19e-110.2860.47Mono/MacroNA

ENG

ENSG00000106991-0.30791.35e-162.12e-120.1510.324Mono/MacroNA

PTMA

ENSG00000187514-0.3099911.83e-132.89e-090.8960.941Mono/MacroNA

CAPN2

ENSG00000162909-0.3105182.48e-203.90e-160.210.425Mono/MacroNA

HNRNPA2B1

ENSG00000122566-0.3117492.67e-204.21e-160.7170.86Mono/MacroNA

TUBA1C

ENSG00000167553-0.3121751.03e-211.63e-170.0890.286Mono/MacroNA

TAGLN2

ENSG00000158710-0.3137383.21e-145.06e-100.4760.658Mono/MacroNA

ACSL3

ENSG00000123983-0.3146181.09e-191.72e-150.1210.314Mono/MacroNA

HMGN2

ENSG00000198830-0.3156791.39e-102.20e-060.4740.622Mono/MacroNA

ATP5MD

NA-0.3157131.37e-162.15e-120.2470.432Mono/MacroNA

RANBP2

ENSG00000153201-0.3171172.53e-213.99e-170.2340.467Mono/MacroNA

AP2S1

ENSG00000042753-0.3177012.61e-184.12e-140.3220.529Mono/MacroNA

RHOA

ENSG00000067560-0.3191674.45e-167.02e-120.5280.718Mono/MacroNA

TNFRSF1A

ENSG00000067182-0.3195281.95e-173.07e-130.2840.48Mono/MacroNA

SH3BP5

ENSG00000131370-0.3200848.82e-221.39e-170.1360.352Mono/MacroNA

FGL2

ENSG00000127951-0.3201557.67e-201.21e-150.0990.286Mono/MacroNA

NDUFA3

ENSG00000276061-0.3202652.76e-244.35e-200.1340.361Mono/MacroNA

EIF4E

ENSG00000151247-0.3205167.74e-241.22e-190.0910.302Mono/MacroNA

LIMS1

ENSG00000169756-0.3205263.31e-205.22e-160.1510.353Mono/MacroNA

IQGAP1

ENSG00000140575-0.321093.56e-195.61e-150.5130.725Mono/MacroNA

PPT1

ENSG00000131238-0.3224153.48e-185.49e-140.3220.52Mono/MacroNA

PNPLA8

ENSG00000135241-0.3230267.24e-201.14e-150.1970.405Mono/MacroNA

CFL1

ENSG00000172757-0.3231894.54e-177.15e-130.7530.87Mono/MacroNA

CFP

ENSG00000126759-0.3241582.11e-193.33e-150.4110.625Mono/MacroNA

RPL27A

ENSG00000166441-0.3243892.20e-183.46e-140.820.9Mono/MacroNA

SLC25A37

ENSG00000147454-0.3250171.43e-172.25e-130.630.796Mono/MacroNA

SEC61B

ENSG00000106803-0.3250414.02e-186.34e-140.4540.658Mono/MacroNA

UQCRC1

ENSG00000010256-0.3252843.10e-234.89e-190.1390.357Mono/MacroNA

VAPA

ENSG00000101558-0.325411.55e-172.44e-130.580.778Mono/MacroNA

HLA-DRB1

ENSG00000228080-0.3257571.17e-251.84e-210.6410.847Mono/MacroNA

POLR2L

ENSG00000177700-0.3257941.93e-153.03e-110.4330.615Mono/MacroNA

HLA-DRA

ENSG00000277263-0.3264962.65e-224.18e-180.7360.892Mono/MacroNA

CALM1

ENSG00000198668-0.328379.25e-181.46e-130.3850.587Mono/MacroNA

RPL39

ENSG00000198918-0.3285572.58e-134.06e-090.9140.948Mono/MacroNA

ANKH

ENSG00000154122-0.3290442.86e-234.50e-190.0560.252Mono/MacroNA

NRIP1

ENSG00000180530-0.3292061.97e-153.11e-110.3550.537Mono/MacroNA

IRAK1

ENSG00000184216-0.3293956.91e-191.09e-140.2270.434Mono/MacroNA

TALDO1

ENSG00000177156-0.3308782.09e-173.30e-130.3220.517Mono/MacroNA

NRGN

ENSG00000154146-0.3309892.32e-213.66e-170.2250.443Mono/MacroNA

LPAR6

ENSG00000139679-0.3315921.28e-132.01e-090.1880.343Mono/MacroNA

ANXA11

ENSG00000122359-0.3329045.53e-228.72e-180.3460.588Mono/MacroNA

RPS21

ENSG00000171858-0.3340932.21e-163.49e-120.790.872Mono/MacroNA

TLR2

ENSG00000137462-0.3348469.48e-211.49e-160.2660.497Mono/MacroNA

MS4A7

ENSG00000166927-0.3355119.58e-221.51e-170.1360.347Mono/MacroNA

CAPNS1

ENSG00000126247-0.3369122.20e-203.47e-160.3640.587Mono/MacroNA

CTDSP1

ENSG00000144579-0.3369482.13e-213.36e-170.1840.403Mono/MacroNA

IRS2

ENSG00000185950-0.3382212.50e-213.95e-170.1320.337Mono/MacroNA

CXCL2

ENSG00000081041-0.338769.02e-071.42e-020.2190.327Mono/MacroNA

ARPC3

ENSG00000111229-0.3418121.90e-173.00e-130.5520.778Mono/MacroNA

GNA15

ENSG00000060558-0.3435666.16e-249.71e-200.2750.523Mono/MacroNA
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Mechanism analysis of drug resistance-related DEGs for each cell type in the pre-treatment samples

check buttonEnrichment 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.)

check buttonHallmark, 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.)

check buttonHallmark, 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

check buttonEnrichment 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.)

check buttonHallmark, 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.)

check buttonHallmark, 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

check buttonThis 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
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MechnismPvalFDRSignatureGenesetOverlapBackgroundCell typeEnriched Genes
Unusual Activation of Pro-survival Pathway5.90e-022.90e-0112781223467Malignant cellsEGR1,CXCL8
Epigenetic Alteration of DNA, RNA or Protein2.10e-015.20e-0112455123467Malignant cellsCXCL8
Aberration of the Drug's Therapeutic Target1.00e+001.00e+001290023467Malignant cells
Drug Inactivation by Structure Modification1.00e+001.00e+001227023467Malignant cells
Irregularity in Drug Uptake and Drug Efflux1.00e+001.00e+001237023467Malignant cells

Enrichment results for 1 known drug resistance mechanisms in TME cells

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MechnismPvalFDRSignatureGenesetOverlapBackgroundCell typeEnriched Genes
Regulation by the Disease Microenvironment1.00e+001.00e+003186023467B cellsNA
Regulation by the Disease Microenvironment6.60e-036.60e-03148186523467CD4+ T cellsBRAF,TGFB1,SOCS3,VIM,ZEB1
Regulation by the Disease Microenvironment1.80e-011.80e-01276186423467CD8+ T cellsNFKB1,TGFB1,CXCR4,VIM
Regulation by the Disease Microenvironment5.10e-015.10e-01467186423467ErythrocytesBCL2L1,MTDH,HNRNPA2B1,MALAT1
Regulation by the Disease Microenvironment9.20e-039.20e-035241861023467Mono_MacroBRAF,CTNNB1,TGFB1,VEGFA,ZEB2,IL1B,HNRNPA2B1,SOCS3,VIM,MALAT1
Regulation by the Disease Microenvironment4.80e-014.80e-0181186123467NK cellsVIM

check buttonHallmark, 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 HallmarkUp-regulated KEGGUp-regulated GO BP

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check buttonHallmark, 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 HallmarkDown-regulated KEGGDown-regulated GO BP

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

check buttonIn 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.)

check buttonIn 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.)

check buttonThis 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 groupRegulating 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.boxplot

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

check buttonIn 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.)

check buttonIn 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.)

check buttonThis 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
motifmotifNESAUCTF_highConfCell_type
motiftransfac_pro__M028484.050.193EGR1 (inferredBy_Orthology). CD4+ T cells
motiftaipale_tf_pairs__ETV5_HES7_NNCACGTGNNNNCCGGAANN_CAP4.020.192ETV5; HES7 (directAnnotation). CD4+ T cells
motiftransfac_pro__M074753.810.185TBX5 (inferredBy_Orthology). CD4+ T cells
motifcisbp__M007753.790.184ZBTB1 (inferredBy_Orthology). CD4+ T cells
motifmetacluster_84.23.760.183RARA (directAnnotation). CD4+ T cells
motiftaipale_tf_pairs__E2F1_ELK1_SGCGCNNNNNNNNNNCGGAAGN_CAP_repr3.740.182E2F1; ELK1 (directAnnotation). CD4+ T cells
motifmetacluster_141.53.710.181NR3C1; 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
motifjaspar__MA1650.13.680.18ZBTB14 (directAnnotation). CD4+ T cells
motiftransfac_pro__M020903.620.178E2F4 (directAnnotation). CD4+ T cells
motiftransfac_pro__M080053.560.176TCFL5 (inferredBy_Orthology). CD4+ T cells
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Motifs and TFs regulating down-regulated DEGs in resistant group
motifmotifNESAUCTF_highConfCell_type
motiftransfac_pro__M012527.710.61E2F6 (directAnnotation). B cells
motiftfdimers__MD003107.020.558IKZF1; OTX1; OTX2 (directAnnotation). B cells
motifmetacluster_76.16.650.53ZNF345; ZNF345 (directAnnotation). MYB; MYBL1 (inferredBy_Orthology). B cells
motifmetacluster_156.26.560.523ATF3; ATF4; ATF4; ATF4; ATF4; ATF4; ATF4; CEBPG; CEBPG; DDIT3; MYC (directAnnotation). ATF4; ATF4; ATF4; CEBPG; DDIT3 (inferredBy_Orthology). B cells
motiftransfac_pro__M055316.50.518IKZF5 (inferredBy_Orthology). B cells
motiftfdimers__MD001036.440.514ZNF333 (directAnnotation). B cells
motifcisbp__M008386.020.482FOXP1 (directAnnotation). B cells
motifmetacluster_130.15.990.48ZNF713; ZNF713 (directAnnotation). HSF1; HSF2; HSF4; HSF5; HSFX1; HSFX2; HSFX3; HSFX4; HSFY1; HSFY2 (inferredBy_Orthology). B cells
motifmetacluster_139.95.890.473TFE3 (inferredBy_Orthology). B cells
motiftfdimers__MD002985.880.471CEBPA; CEBPB; CEBPD; CEBPE; CEBPG; FOXL1 (directAnnotation). B cells
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Differentially expressed genes act as transcription factors

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

ZEB1

tfdimers__MD00527upCD4+ T cellsNA

MECP2

metacluster_135.10upCD8+ T cellsNA

E2F4

metacluster_45.6downErythrocytesNA

KLF13

hocomoco__KLF13_HUMAN.H11MO.0.DdownErythrocytesNA

YBX1

metacluster_79.33downErythrocytesNA

BACH1

metacluster_22.37upMono/MacroNA

BACH1

metacluster_157.2upMono/MacroNA

BACH1

metacluster_30.4upMono/MacroNA

EGR1

cisbp__M01864upMono/MacroNA

EGR1

metacluster_131.7upMono/MacroNA
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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."