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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

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

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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: GSE207422_Sin

Dataset summary for GSE207422_Sin

Datast informationDatasetGSE207422_Sin
PMID36869384
Raw data ID/linkhttps://ngdc.cncb.ac.cn/gsa-human/browse/HRA001033
OrganismHomo sapiens
Sourcepatients
TissueTumor tissue
Cancer type level1Lung cancer
Cancer type level2EGFR/ALK mutation negative non-small cell lung cancer (NSCLC)
Regimensintilimab + carboplatin + (docetaxel or pemetrexed or emcitabine)
Drug typeImmunotherapy
Sample sizepost (resistant 5, sensitive 2)
Cell number22187
Extract protocolBD Rhapsody system
Data processing BD Rhapsody Whole Transcriptome Analysis (WTA) Pipeline
Public datePublic on Mar 21, 2023
DescriptionThis dataset has 7 patients with post-treatment samples.

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Drug summary for GSE207422_Sin

Drug nameDrugBank IDDrug typeTargets nameTargets uniprot ID
"Sintilimab"

DB15765

biotechPDCD1Q15116
"carboplatin" is not included in the drug list.
"Docetaxel"

DB01248

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

DB00642

small moleculeTYMS; ATIC; DHFR; GARTP04818; P31939; P00374; P22102
"emcitabine" 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.)

resistant vs. sensitive

boxplot
Dot plot of significant ligand-receptor pairs in the resistant groupDot plot of significant ligand-receptor pairs in the sensitive group
boxplotboxplot

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.
Gene symbolGene idavg_log2FCp_valp_val_adjpct.1pct.2Cell typeTimepoint

FKBP5

ENSG000000960601.309990.00e+000.00e+000.4810.07Neutrophilspost

CLEC4E

ENSG000001665231.228550.00e+000.00e+000.770.486Neutrophilspost

ALOX5AP

ENSG000001329651.198470.00e+000.00e+000.840.641Neutrophilspost

GRINA

ENSG000001787191.128040.00e+000.00e+000.560.163Neutrophilspost

FCER1G

ENSG000001588691.060040.00e+000.00e+000.8710.658Neutrophilspost

HLA-DRA

ENSG000002772631.05489.51e-432.28e-380.8380.52Neutrophilspost

IL1R2

ENSG000001155901.03596.73e-321.62e-270.6060.41Neutrophilspost

TNFAIP3

ENSG000001185030.9061221.13e-332.71e-290.4630.178Neutrophilspost

NFKBIA

ENSG000001009060.8972857.15e-421.72e-370.790.497Neutrophilspost

CCRL2

ENSG000001217970.882776.07e-361.46e-310.3570.068Neutrophilspost

C15orf48

ENSG000001669200.8641386.40e-231.54e-180.2590.057Neutrophilspost

CDKN1A

ENSG000001247620.8439369.83e-282.36e-230.2950.059Neutrophilspost

CTSB

ENSG000002851320.8385270.00e+006.52e-430.6910.342Neutrophilspost

CXCL16

ENSG000001619210.7866381.24e-292.98e-250.5690.34Neutrophilspost

TRIM22

ENSG000001322740.7828686.86e-351.65e-300.4860.212Neutrophilspost

IER3

ENSG000002350300.7308462.17e-255.20e-210.5130.272Neutrophilspost

CD74

ENSG000000195820.7249425.28e-121.27e-070.9860.928Neutrophilspost

CEBPD

ENSG000002218690.7196352.23e-165.35e-120.6290.518Neutrophilspost

SMIM25

NA0.713833.07e-347.37e-300.5970.338Neutrophilspost

PLSCR1

ENSG000001883130.7136845.22e-301.25e-250.4750.214Neutrophilspost

ANKRD22

ENSG000001527660.7065644.77e-301.15e-250.2520.019Neutrophilspost

IGKC

ENSG000002115920.6944997.58e-151.82e-100.3450.183Neutrophilspost

PHC2

ENSG000001346860.6914763.03e-287.27e-240.5120.293Neutrophilspost

GBP5

ENSG000001544510.6748781.00e-142.40e-100.530.372Neutrophilspost

SAMSN1

ENSG000001553070.6358081.65e-283.97e-240.4310.166Neutrophilspost

CYBB

ENSG000001651680.6337135.54e-171.33e-120.3910.21Neutrophilspost

CPD

ENSG000001085820.6323644.84e-211.16e-160.4780.297Neutrophilspost

FLOT1

ENSG000002236540.6264814.61e-261.11e-210.490.278Neutrophilspost

IFITM3

ENSG000001420890.6211072.73e-146.56e-100.8650.864Neutrophilspost

GRN

ENSG000000305820.6198541.48e-203.56e-160.5230.329Neutrophilspost

TSC22D3

ENSG000001575140.6101877.48e-101.80e-050.6640.662Neutrophilspost

CCL4L2

ENSG000002826040.6036982.28e-145.47e-100.2990.142Neutrophilspost

GBP4

ENSG000001626540.5892322.53e-166.07e-120.3880.208Neutrophilspost

HMGB2

ENSG000001641040.5862046.07e-081.46e-030.3520.261Neutrophilspost

TXNIP

ENSG000002659720.5793522.23e-165.36e-120.9510.947Neutrophilspost

CD53

ENSG000001431190.5789657.72e-301.85e-250.7810.654Neutrophilspost

BHLHE40

ENSG000001341070.5763481.96e-214.70e-170.3060.1Neutrophilspost

IFI6

ENSG000001267090.5736626.50e-191.56e-140.6340.427Neutrophilspost

BRI3

ENSG000001647130.5717462.07e-224.98e-180.6970.567Neutrophilspost

SLA

ENSG000001559260.5683071.21e-202.92e-160.6320.465Neutrophilspost

WSB1

ENSG000001090460.547271.59e-183.82e-140.4720.282Neutrophilspost

CTSD

ENSG000001179840.5375172.56e-096.14e-050.350.238Neutrophilspost

IFIT3

ENSG000001199170.5304953.30e-087.94e-040.5360.446Neutrophilspost

CEBPB

ENSG000001722160.524121.06e-222.55e-180.8950.817Neutrophilspost

TLR2

ENSG000001374620.515683.04e-187.30e-140.560.414Neutrophilspost

RAB20

ENSG000001398320.5054892.03e-224.87e-180.2690.066Neutrophilspost

IRS2

ENSG000001859500.4874555.69e-161.37e-110.4320.261Neutrophilspost

CD44

ENSG000000265080.4844171.01e-082.42e-040.330.225Neutrophilspost

IFNGR1

ENSG000000276970.4804988.35e-182.01e-130.5310.365Neutrophilspost

SKIL

ENSG000001366030.4801052.07e-154.97e-110.3440.178Neutrophilspost
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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.

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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.)
Enrichment results for 5 known drug resistance mechanisms in malignant cells
boxplot
MechnismPvalFDRSignatureGenesetOverlapBackgroundCell typeEnriched Genes
Unusual Activation of Pro-survival Pathway1.10e-035.30e-031997811623467Malignant cellsCDKN1A,GSTP1,SLC2A1,HSPA1A,ID1,YWHAZ,FOXA1,GAPDH,LDHA,LRIG1,NOTCH3,NQO1,RAC1,UCP2,ENO1,ALDH1A1
Drug Inactivation by Structure Modification2.10e-014.50e-0119927123467Malignant cellsGSTP1
Irregularity in Drug Uptake and Drug Efflux2.70e-014.50e-0119937123467Malignant cellsSLC2A1
Epigenetic Alteration of DNA, RNA or Protein9.80e-011.00e+00199455123467Malignant cellsGAPDH
Aberration of the Drug's Therapeutic Target1.00e+001.00e+0019990023467Malignant cells

Enrichment results for 1 known drug resistance mechanisms in TME cells

boxplot
MechnismPvalFDRSignatureGenesetOverlapBackgroundCell typeEnriched Genes
Regulation by the Disease Microenvironment3.90e-013.90e-01168186223467B cellsTP53INP1,CXCR4
Regulation by the Disease Microenvironment2.00e-012.00e-01194186323467CD4+ T cellsCXCR4,FYN,SOCS3
Regulation by the Disease Microenvironment3.00e-013.00e-01349186423467CD8+ T cellsCXCR4,RHOB,SOCS3,MALAT1
Regulation by the Disease Microenvironment1.00e+001.00e+007186023467FibroblastsNA
Regulation by the Disease Microenvironment1.00e+001.00e+0041186023467Mast cellsNA
Regulation by the Disease Microenvironment3.00e-013.00e-01456186523467Mono_MacroVEGFA,CXCR4,SOCS3,VIM,FBP1
Regulation by the Disease Microenvironment3.50e-013.50e-01266186323467NeutrophilsPAK1,CXCR4,RHOB
Regulation by the Disease Microenvironment1.90e-021.90e-0227186223467NK cellsCX3CR1,CXCR4
Regulation by the Disease Microenvironment9.20e-029.20e-0264186223467pDCsCX3CR1,CXCR4
Regulation by the Disease Microenvironment1.00e+001.00e+0058186023467Plasma cellsNA

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.)
Up-regulated HallmarkUp-regulated KEGGUp-regulated GO BP
boxplotboxplotboxplot

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.)
Down-regulated HallmarkDown-regulated KEGGDown-regulated GO BP
There is no signaficant down-regulated pathways in resistant groupboxplotboxplot

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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.)

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.)

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.)

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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.)
Regulating up-regulated DEGs in resistant groupRegulating down-regulated DEGs in resistant group
boxplotboxplot

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.)

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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.)
Motifs and TFs regulating up-regulated DEGs in resistant group of the post-treatment samples
motifmotifNESAUCTF_highConfCell_type
motifhocomoco__TYY2_HUMAN.H11MO.0.D4.860.0798YY2 (directAnnotation). B cells
motiftransfac_pro__M020804.550.0762ISL2 (directAnnotation). B cells
motifmetacluster_141.24.330.0737E2F2; E2F3 (directAnnotation). B cells
motiftransfac_pro__M065004.190.0722ZNF614 (directAnnotation). B cells
motiftaipale_tf_pairs__ETV2_HES7_RSCGGAANNNNNNNCACGTGNN_CAP_repr4.180.072ETV2; HES7 (directAnnotation). B cells
motiftransfac_pro__M063014.060.0706ZNF404 (directAnnotation). B cells
motiftaipale__YY2_DBD_NNCCGCCATNW_repr3.850.0683YY2 (directAnnotation). B cells
motiftaipale_tf_pairs__ELK1_TEF_NSCGGAWNTTACGTAAN_CAP3.730.0669ELK1; TEF (directAnnotation). B cells
motiftfdimers__MD000323.660.0661GFI1; GFI1B; NKX3-2 (directAnnotation). B cells
motiftaipale_cyt_meth__JUND_NRTGACGCATN_eDBD_repr3.640.0658JUND (directAnnotation). B cells
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Motifs and TFs regulating down-regulated DEGs in resistant group of the post-treatment samples
motifmotifNESAUCTF_highConfCell_type
motiftransfac_pro__M057315.270.232ZNF660 (directAnnotation). B cells
motiftransfac_pro__M060374.570.206ZNF197 (directAnnotation). B cells
motifmetacluster_103.24.480.203ZNF136; ZNF680 (directAnnotation). B cells
motiftransfac_pro__M055424.290.196SNAPC4 (directAnnotation). B cells
motiftransfac_pro__M065394.180.192ZNF483 (directAnnotation). B cells
motifmetacluster_52.133.940.183LEF1; LEF1; LEF1; LEF1; TCF7; TCF7; TCF7L1; TCF7L1 (directAnnotation). B cells
motiftfdimers__MD003753.820.179KLF4; PITX3 (directAnnotation). B cells
motiftransfac_pro__M066613.820.179ZNF426 (directAnnotation). B cells
motiftransfac_pro__M058213.490.167ZNF880 (directAnnotation). B cells
motiftaipale__ZNF524_full_ACCCTTGAACCC_repr3.470.166ZNF524 (directAnnotation). B cells
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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.)

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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

KLF2

metacluster_163.1upB cellspost

KLF2

metacluster_170.2upB cellspost

CREM

transfac_pro__M00801upCD4+ T cellspost

IKZF2

tfdimers__MD00029upCD4+ T cellspost

TCF7

metacluster_52.13downCD4+ T cellspost

JUND

taipale_cyt_meth__JUND_NRTGACGCATN_eDBD_reprupCD8+ T cellspost

PRDM1

metacluster_2.9upCD8+ T cellspost

FOXP1

hocomoco__FOXP1_HUMAN.H11MO.0.AdownMast cellspost

CEBPD

taipale_tf_pairs__ETV2_CEBPD_RSCGGANNTTGCGYAAN_CAP_reprupMono/Macropost

FOSL2

metacluster_157.2upMono/Macropost
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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."