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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 (This dataset does not contain this module)

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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: GSE131984_Pac

Dataset summary for GSE131984_Pac

Datast informationDatasetGSE131984_Pac
PMID32393766
Raw data ID/linkPRJNA545508
OrganismHomo sapiens
SourceSUM159 cell line
TissueCell line
Cancer type level1Breast cancer
Cancer type level2Triple-negative breast cancer (TNBC)
Regimenpaclitaxel
Drug typeChemotherapy
Sample sizeresistant 1, sensitive 2
Cell number1813
Extract protocol10x genomics
Data processingCellRanger 2.1.0
Public datePublic on Apr 08, 2020
DescriptionThis dataset has 1 cell line with 2 sensitive pre-treatment samples and 1 resistant post-treatment sample.

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Drug summary for GSE131984_Pac

Drug nameDrugBank IDDrug typeTargets nameTargets uniprot ID
"Paclitaxel"

DB01229

small moleculeTUBB1; BCL2; MAP4; MAP2; MAPT; NR1I2Q9H4B7; P10415; P27816; P11137; P10636; O75469

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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
Umap of cell clustersboxplotCell ratio of drug-resistant and sensitive groups within each clusterboxplot

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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.)

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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

DUSP1

ENSG00000120129-0.7475871.90e-332.93e-290.5240.725Malignant cellsNA

NEAT1

ENSG00000245532-0.749121.03e-401.60e-360.9910.992Malignant cellsNA

AKR1B1

ENSG00000085662-0.8075820.00e+000.00e+0011Malignant cellsNA

HSPB1

ENSG00000106211-0.8088050.00e+000.00e+000.9710.992Malignant cellsNA

CEBPD

ENSG00000221869-0.8416110.00e+000.00e+000.7390.892Malignant cellsNA

IER2

ENSG00000160888-0.8461890.00e+000.00e+000.6210.828Malignant cellsNA

TUBA1A

ENSG00000167552-0.9084044.61e-367.10e-320.5310.713Malignant cellsNA

SOD2

ENSG00000291237-0.9388320.00e+000.00e+000.8630.952Malignant cellsNA

PNRC1

ENSG00000146278-0.9974510.00e+000.00e+000.3480.719Malignant cellsNA

NFKBIA

ENSG00000100906-1.033560.00e+000.00e+000.8160.96Malignant cellsNA

SCD

ENSG00000099194-1.059240.00e+000.00e+000.560.877Malignant cellsNA

JUNB

ENSG00000171223-1.10850.00e+000.00e+000.4560.808Malignant cellsNA

CXCL3

ENSG00000163734-1.120712.36e-423.65e-380.1490.436Malignant cellsNA

INSIG1

ENSG00000186480-1.164980.00e+000.00e+000.3630.811Malignant cellsNA

CYR61

NA-1.189440.00e+000.00e+000.6570.857Malignant cellsNA

IL6

ENSG00000136244-1.226910.00e+000.00e+000.1880.557Malignant cellsNA

EGR1

ENSG00000120738-1.240470.00e+000.00e+000.3010.747Malignant cellsNA

IER3

ENSG00000235030-1.240810.00e+000.00e+000.9640.994Malignant cellsNA

CXCL2

ENSG00000081041-2.11350.00e+000.00e+000.4720.899Malignant cellsNA

IL8

NA-2.839230.00e+000.00e+000.3950.91Malignant cellsNA
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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
boxplot
MechnismPvalFDRSignatureGenesetOverlapBackgroundCell typeEnriched Genes
Unusual Activation of Pro-survival Pathway1.10e-095.50e-098707816523467Malignant cellsAURKA,BBC3,BIRC5,CDK4,CFLAR,DNMT1,FADD,HMGA1,ID1,IFI27,IL6,ISG15,JUN,MAP1LC3B,PDGFRA,S100A4,STMN1,TIMP3,SLC25A5,ANXA1,BAG1,BTG1,CCND1,CCNG1,HSPD1,COL1A1,DKK1,DUSP1,EGR1,EIF3A,FUS,HNRNPU,HSPA8,HSPB1,IDH1,EIF4E,NFKBIA,IL18,LAMP2,MTDH,MAP3K8,MXD4,NF2,MYO10,PLK1,HRAS,RRM2,S100A11,SFPQ,SMC4,SOD2,TFAM,TMED3,TNFAIP3,TOP1,UBE2C,FASN,CEBPD,IDI1,INSIG1,SPHK1,SAFB2,EBP,NUPR1,ACAT2
Irregularity in Drug Uptake and Drug Efflux4.70e-021.20e-0187037423467Malignant cellsABCF2,ABCE1,SLC7A5,SLC29A1
Drug Inactivation by Structure Modification7.70e-021.30e-0187027323467Malignant cellsSOD2,CDA,NME1
Aberration of the Drug's Therapeutic Target2.40e-013.00e-0187090523467Malignant cellsCDK4,PDGFRA,IDH1,MAOA,AKR1B1
Epigenetic Alteration of DNA, RNA or Protein9.50e-019.50e-018704551123467Malignant cellsDNMT1,EIF4G2,IL6,PMAIP1,IDH1,MAP3K8,SMC4,TIMP1,MALAT1,PPP1R15A,DLEU1


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
boxplotboxplot

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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
motiftaipale_tf_pairs__ETS2_RCCGGAAGTG_HT5.520.0588ETS2 (directAnnotation). Malignant cells
motifmetacluster_34.45.390.0579ETS1; ETS1; ETS1; HCFC1; SIX5; SIX5; SIX5; SIX5; SMARCC2; SMARCC2; THAP11; THAP11; ZNF143; ZNF143; ZNF143; ZNF143 (directAnnotation). TBX2; THAP11; THAP11; ZNF143 (inferredBy_Orthology). Malignant cells
motiftaipale_tf_pairs__MEIS1_ELF1_NTGCCGGAAGTN_CAP_repr4.830.0541ELF1; MEIS1 (directAnnotation). Malignant cells
motifmetacluster_166.24.460.0516ELK4; ETS1; ETS1; ETV1; ETV3; ETV4; ETV5; ETV7 (directAnnotation). GABPA (inferredBy_Orthology). Malignant cells
motifmetacluster_191.34.260.0503EHF; ELF1; ELF1; ELF1; ELF4; ELK1; ELK3; ELK3; ELK4; ELK4; ERF; ETS1; ETS2; ETV3; ETV4; ETV5; FEV; FEV; FLI1; FLI1; GABPA; GABPA; GABPA; GABPA; GABPA; GABPA; SPDEF; ZNF200 (directAnnotation). ELK1; ELK1; ELK3; ELK3; ELK4; ELK4; ETV1; ETV1; ETV4; ETV4; ETV4; ETV5; GABPA; GABPA (inferredBy_Orthology). Malignant cells
motifmetacluster_34.34.240.0501EGR1; ETS1; SETDB1; SIX5; SIX5; ZNF143; ZNF76 (directAnnotation). Malignant cells
motifmetacluster_191.24.20.0499ELK4; NR2C2; NR2C2; NR2C2; NR2C2 (directAnnotation). GABPA (inferredBy_Orthology). Malignant cells
motifjaspar__MA1483.24.020.0486ELF2 (directAnnotation). Malignant cells
motiftaipale_tf_pairs__ETV5_HOXA2_RSCGGWAATKR_CAP3.920.0479ETV5; HOXA2 (directAnnotation). Malignant cells
motifmetacluster_166.43.880.0477BCLAF1; 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). Malignant cells
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Motifs and TFs regulating down-regulated DEGs in resistant group
motifmotifNESAUCTF_highConfCell_type
motifmetacluster_22.295.250.0693NFE2 (directAnnotation). Malignant cells
motifmetacluster_174.35.140.0685MBD2; NFYA; NFYB; NFYC; PBX3 (directAnnotation). Malignant cells
motifmetacluster_22.254.840.066NFE2L2 (directAnnotation). Malignant cells
motifmetacluster_2.74.810.0658IRF1; IRF1; IRF2; IRF2; IRF3; IRF4; IRF5; IRF6; IRF7; IRF7; IRF8; IRF8; IRF9; PRDM1; PRDM1; PRDM1; PRDM1; PRDM1; PRDM1; PRDM1; PRDM1; PRDM1; PRDM1; PRDM1; PRDM1; STAT1; STAT1; STAT2 (directAnnotation). PRDM1; PRDM1; PRDM1 (inferredBy_Orthology). Malignant cells
motifmetacluster_22.124.660.0645NFE2; NFE2L1 (directAnnotation). Malignant cells
motifjaspar__MA0502.24.510.0633NFYB (directAnnotation). Malignant cells
motifmetacluster_22.184.490.0632BACH2 (inferredBy_Orthology). Malignant cells
motifjaspar__MA0604.14.460.063ATF1 (inferredBy_Orthology). Malignant cells
motifhomer__GGAAATTCCC_NFkB-p65-Rel4.450.0629RELA (inferredBy_Orthology). Malignant cells
motifmetacluster_22.324.410.0626NFE2L2 (directAnnotation). Malignant 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

CEBPZ

metacluster_174.2upMalignant cellsNA

TEAD4

taipale_tf_pairs__TEAD4_HOXA13_GGWATGNNNRTAAA_CAP_reprupMalignant cellsNA

TEAD4

taipale_tf_pairs__TEAD4_DRGX_GGAATGTTAATTR_CAPupMalignant cellsNA

FOSL1

metacluster_137.2upMalignant cellsNA

PITX1

taipale_tf_pairs__TEAD4_PITX1_RCATWCNNNNNGGATTA_CAP_reprupMalignant cellsNA

TEAD4

taipale_tf_pairs__TEAD4_PITX1_RCATWCNNNNNGGATTA_CAP_reprupMalignant cellsNA

TEAD4

taipale_tf_pairs__TEAD4_HOXB13_GGWATGNNNRTAAA_CAPupMalignant cellsNA

TEAD4

taipale_tf_pairs__TEAD4_ETV4_RCCGGAAATRCC_CAPupMalignant cellsNA

TEAD4

taipale_tf_pairs__TEAD4_ERG_RSCGGAAATRCC_CAP_reprupMalignant cellsNA

TEAD4

taipale_tf_pairs__TEAD4_ERG_RSCGGAAATRCC_CAPupMalignant cellsNA
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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."