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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

ADH5

ENSG000001978940.3305858.09e-141.27e-090.3260.089CD8+ T cellsNA

RPL29

ENSG000001622440.3283951.49e-082.35e-040.9860.98CD8+ T cellsNA

COX7A2

ENSG000001126950.3268824.18e-086.59e-040.5870.333CD8+ T cellsNA

PPDPF

ENSG000001255340.3265684.07e-076.42e-030.5220.31CD8+ T cellsNA

RPL24

ENSG000001143910.3255626.57e-091.04e-040.9890.936CD8+ T cellsNA

SSBP1

ENSG000002627710.32481.38e-102.18e-060.4280.183CD8+ T cellsNA

ANKRD12

ENSG000001017450.323012.34e-073.68e-030.7860.567CD8+ T cellsNA

FAU

ENSG000001498060.3210628.96e-101.41e-050.9960.99CD8+ T cellsNA

NDUFA1

ENSG000001253560.3206359.96e-091.57e-040.5250.28CD8+ T cellsNA

RPL13A

ENSG000001425410.3171516.47e-101.02e-050.9960.972CD8+ T cellsNA

VPS26A

ENSG000001229580.3167716.00e-119.45e-070.3220.109CD8+ T cellsNA

RPS23

ENSG000001864680.3161319.24e-081.46e-030.9890.992CD8+ T cellsNA

RAB5IF

ENSG000001010840.3140426.88e-091.09e-040.4060.191CD8+ T cellsNA

PARK7

ENSG000001162880.3127554.77e-107.52e-060.3880.163CD8+ T cellsNA

COPE

ENSG000001056690.3116953.57e-105.62e-060.4860.221CD8+ T cellsNA

RAP1B

ENSG000001273140.3113513.91e-076.16e-030.5540.331CD8+ T cellsNA

CTSC

ENSG000001098610.3102131.11e-081.74e-040.3190.135CD8+ T cellsNA

RPL31

ENSG000000710820.3095157.97e-081.26e-030.8620.692CD8+ T cellsNA

TOMM7

ENSG000001966830.3085234.73e-077.45e-030.7610.504CD8+ T cellsNA

UQCRH

ENSG000001736600.3081091.63e-082.56e-040.5140.265CD8+ T cellsNA

SSR2

ENSG000001634790.3058472.33e-063.67e-020.5290.326CD8+ T cellsNA

RPL32

ENSG000001447130.3045455.45e-088.60e-040.9961CD8+ T cellsNA

RPS19BP1

ENSG000001870510.3040918.94e-091.41e-040.3660.165CD8+ T cellsNA

CNOT6L

ENSG000001387670.3006693.56e-075.61e-030.5620.323CD8+ T cellsNA

CMIP

ENSG000001538150.3000143.30e-085.20e-040.2680.102CD8+ T cellsNA

RPL4

ENSG000001744440.2990285.15e-078.12e-030.9060.791CD8+ T cellsNA

NDUFA4

ENSG000001890430.2985581.20e-061.89e-020.6230.407CD8+ T cellsNA

EIF3D

ENSG000001003530.2983576.39e-091.01e-040.3840.17CD8+ T cellsNA

SNRPD2

ENSG000001257430.2982151.36e-072.14e-030.420.216CD8+ T cellsNA

C11orf58

ENSG000001106960.2973592.31e-093.64e-050.4350.196CD8+ T cellsNA

NDUFA6

ENSG000002773650.2955099.10e-081.43e-030.3660.176CD8+ T cellsNA

EIF3H

ENSG000001476770.2953371.14e-081.79e-040.4890.244CD8+ T cellsNA

IL10RA

ENSG000001103240.2952381.75e-082.76e-040.2830.107CD8+ T cellsNA

PSMB8

ENSG000002306690.2951221.08e-091.70e-050.3410.137CD8+ T cellsNA

GOLGA7

ENSG000001475330.2924248.72e-101.37e-050.2540.079CD8+ T cellsNA

TMSB4X

ENSG000002055420.2921642.35e-083.70e-0410.995CD8+ T cellsNA

UXT

ENSG000001267560.2897973.19e-075.02e-030.3910.204CD8+ T cellsNA

GUK1

ENSG000001437740.2896332.11e-063.32e-020.6410.427CD8+ T cellsNA

KLRG1

ENSG000001391870.2891181.08e-091.70e-050.2720.094CD8+ T cellsNA

EEF1D

ENSG000002735940.2882292.17e-063.42e-020.9380.807CD8+ T cellsNA

DDHD1

ENSG000001005230.2874691.87e-072.95e-030.3660.173CD8+ T cellsNA

SERBP1

ENSG000001428640.2866946.77e-071.07e-020.5040.29CD8+ T cellsNA

SMC3

ENSG000001080550.2864681.77e-102.79e-060.3370.122CD8+ T cellsNA

RACK1

ENSG000002046280.2852852.18e-063.43e-020.9310.865CD8+ T cellsNA

PTPN4

ENSG000000881790.2846171.58e-112.48e-070.250.066CD8+ T cellsNA

PLAC8

ENSG000001452870.2836472.93e-104.61e-060.2540.074CD8+ T cellsNA

SLC25A3

ENSG000000754150.2811085.23e-078.25e-030.5830.338CD8+ T cellsNA

MAX

ENSG000001259520.2809014.71e-097.43e-050.3410.142CD8+ T cellsNA

ATP5MC3

ENSG000001545180.2804751.49e-072.35e-030.3840.188CD8+ T cellsNA

PTPRJ

ENSG000001491770.2801641.26e-091.98e-050.3150.117CD8+ T 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
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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."