Skip to content

mepepin/ReductomiRs

Folders and files

NameName
Last commit message
Last commit date

Latest commit

 

History

14 Commits
 
 
 
 
 
 
 
 
 
 

Repository files navigation

title Script Author date output header-includes mainfont fontsize always_allow_html editor_options
Supplemental Methods - ReductomiRs – micro-RNA Signatures in a Reductive Stress Mouse Heart
Mark E. Pepin MD, PhD
12 February, 2021
html_document
keep_md code_folding toc toc_float
true
hide
true
true
\usepackage{booktabs}
\usepackage{longtable}
\usepackage{array}
\usepackage{multirow}
\usepackage[table]{xcolor}
\usepackage{wrapfig}
\usepackage{float}
\usepackage{colortbl}
\usepackage{pdflscape}
\usepackage{tabu}
\usepackage{threeparttable}
Times
10pt
true
markdown
wrap
72

"ReductomiRs – micro-RNA Signatures in a Reductive Stress Mouse Heart"

Justin M. Quiles, Mark E. Pepin, Sini Sunny, Sandeep B. Shelar, Anil K. Challa, Brian Dalley, John R. Hoidal, Steven M. Pogwizd, Adam R. Wende and Namakkal S. Rajasekarana

Transgenic vs. Non-Transgenic Comparison

Data Pre-Processing

After alignment of the fastq files to the annotated genome assembly (mm10), the first step in the analysis is to consolidate the raw data from the provided files into data matrix that can be used to generate a normalized count matrix and differential expression dataset.

Count Normalization

DESeq2 (version 1.18.1) was used to perform the raw count normalization within R (version 3.4.2)

######### RUN DESeq2
dds<-DESeqDataSetFromMatrix(countData=countData, colData = colData, design= ~Transgene)
dds
## class: DESeqDataSet 
## dim: 36855 10 
## metadata(1): version
## assays(1): counts
## rownames(36855): ENSMUSG00000074183 ENSMUSG00000074181 ...
##   ENSMUSG00000064336 ENSMUSG00000064354
## rowData names(0):
## colnames(10): Counts_control0 Counts_control1 ... Counts_TGH1
##   Counts_TGH2
## colData names(3): Sample_ID Transgene Treatment
dds$Transgene<-relevel(dds$Transgene, ref = "NO") # setting the reference to wild-type genotype. only relevant for factors.
#Determine the Dispersion Relationship (determines which distribution to use for the differential analysis) - should take about 2 minutes
dds <- estimateSizeFactors(dds)
dds <- estimateDispersions(dds)
plotDispEsts(dds)

\Dispersion Plot Illustrating the corrective effect of count normalization on the dispersion estimates.

There appears to be a linear negative correlation between the mean and dispersion estimates, so the parametric "Wald" model should be an appropriate fit for differential expression analysis. Furthermore, we could get away with the parametric fit-type, but the run-time is not significantly impaired, allowing us to use the 'local' fit-type. NOTE: If it were nonlinear throughout, we would require a 'local' nonparametric fit-type.

Differential Expression Analysis

##Pre-Filter to reduce the size of this dataset (according to the DESeq2 document reccomendations)
dds <- dds[ rowSums(counts(dds)) > 1, ]
dds
## class: DESeqDataSet 
## dim: 21222 10 
## metadata(1): version
## assays(2): counts mu
## rownames(21222): ENSMUSG00000074183 ENSMUSG00000074181 ...
##   ENSMUSG00000090756 ENSMUSG00000064336
## rowData names(10): baseMean baseVar ... dispOutlier dispMAP
## colnames(10): Counts_control0 Counts_control1 ... Counts_TGH1
##   Counts_TGH2
## colData names(4): Sample_ID Transgene Treatment sizeFactor
################Run DESeq2 differential quantification (Likelihood ratio test (LRT), instead of the wald test - easier for large datasets)
dds<-DESeq(dds, test="Wald", fitType="parametric")
#compile the results tables
res<-DESeq2::results(dds)
resdf<-data.frame(res)
resdf$external_gene_name<-row.names(resdf)
resdf$ensembl_gene_id<-resdf$external_gene_name

Once the differential Expression analysis was performed, the following were compiled into a results data matrix: Log2FoldChange, P-value, Bonferroni-Adjusted P-Value (Q-value), and normalized counts for each sample.

####Add Annotation to the results file (this will take some time, about 5 minutes...)
##Add Gene Information
library(biomaRt)
mmusculus <- biomaRt::useEnsembl(biomart = "ENSEMBL_MART_ENSEMBL",
                                     host = "www.ensembl.org",
                                     dataset = "mmusculus_gene_ensembl",
                                     version = 94)
bm <- getBM(attributes=c("ensembl_gene_id", "external_gene_name", "chromosome_name", "start_position", "end_position"), filter="ensembl_gene_id", values= rownames(dds), mart=mmusculus)
results<-dplyr::left_join(resdf, bm, by = "ensembl_gene_id")
####Add normalized count data (for heatmap and sota)
normcount<-counts(dds)
normcount<-as.data.frame(normcount)
normcount$ensembl_gene_id<-row.names(normcount)
results<-dplyr::left_join(results, normcount, by="ensembl_gene_id")
write.csv(results, "../2_Output/mRNA/results_CaNRF2_mRNA_TG.v.NTG.csv")

QQ Plot

Before we examined the gene networks and pathways differentially regulated by NRF2 knockout, the first task was to determine whether transgene induction resulted in global changes. An effective way of determining this is the QQ plot, which compares the P-value distribution produced by the pairwise comparison (transgenic vs. WT mouse) to that of a random normal distribution. Below, it is evident that the two experimental groups produce robustly divergent expression patterns consistent with a true population difference worthy of differential expression analysis.

#Create Q-Q plot
test<-results
test<-test[complete.cases(test),]
pQQ(test$pvalue, lim=c(0,10))

Heatmap Visualization of Transgenic vs. WT Comparison (P < 0.05)

In order to visualize the distribution of differentially expressed genes, as well as determine the effect of transgenic intensity (TGH vs. TGL), hierarchical clustering and heatmap visualization were performed at the Q < 0.05 statistical level. This analysis reveals that P < 0.05 is sufficient to separate all samples by genotype. In particular, it is apparent that the TGH group display more robust differential expression than TGL when compared to control, in a sort of dose-dependent manner.

library(pheatmap)
results_p05<-filter(results, padj<0.01)
##Index file for annotating samples
rownames(colData)<-colData$Sample_ID
Index<-dplyr::select(colData, Transgene, Treatment)
Index<-as.data.frame(Index)

rownames(results_p05)<-results_p05$external_gene_name.x
counts_p05<-dplyr::select(results_p05, Counts_control0:Counts_TGH2)

paletteLength <- 100
myColor <- colorRampPalette(c("dodgerblue4", "white", "gold2"))(paletteLength)
pheatmap(counts_p05, 
         cluster_cols=T, 
         border_color=NA, 
         cluster_rows=T, 
         scale = 'row', 
         show_colnames = T, 
         show_rownames = F, 
         color = myColor,
         annotation_col = Index)

Principal Components Analysis

Once we established that the populations under consideration truly display divergene expression patterns, we sought to determine whether unbiased global gene expression patterns recapitulate TGL versus TGH phenotypes within the transgenic group. To accomplish this, an unsupervised Principal Components Analysis (PCA) was initially used with normalized counts.

PCA Features

Before running the principal components analysis, it was necessary to first determine the number of PC's required to account for 80% of the variance, a machine-learning algorithmm benchmark that provides sufficient confidence in the analysis.

#Plot Features of the PCA
library(readxl)
library(dplyr)
library(plotly)
##Import the data to be used for PCA
results_DEG<-dplyr::select(results, Counts_control0:Counts_TGH2)
results_DEG<-results_DEG[order(-rowSums(results_DEG)),]
#transpose the dataset (required for PCA)
data.pca<-t(results_DEG)
data.pca<-as.data.frame(data.pca)
##Import the data to be used for annotation
rownames(colData)<-colData$Sample_ID
Index<-dplyr::select(colData, Transgene, Treatment)
Index<-as.data.frame(Index)
##merge the file
data.pca_Final<-merge(Index, data.pca, by=0)
rownames(data.pca_Final)<-data.pca_Final$Row.names
pca.comp<-prcomp(data.pca_Final[,(ncol(Index)+2):ncol(data.pca_Final)])

pcaCharts=function(x) {
    x.var <- x$sdev ^ 2
    x.pvar <- x.var/sum(x.var)
    par(mfrow=c(2,2))
    plot(x.pvar,xlab="Principal component", 
         ylab="Proportion of variance", ylim=c(0,1), type='b')
    plot(cumsum(x.pvar),xlab="Principal component", 
         ylab="Cumulative Proportion of variance", 
         ylim=c(0,1), 
         type='b')
    screeplot(x)
    screeplot(x,type="l")
    par(mfrow=c(1,1))
}
pcaCharts(pca.comp)

3-Dimensional PCA

From the previous calculations, it is seens that only 2 principal components are necessary (accounting for >80% cumulative variance). Nonetheless, below is a 3-D PCA to ensure that all groups are characterize to higher-degree of stringency.

##Create a 3D-PCA for Inspection
PCs<-merge(pca.comp$x, Index, by=0)
rownames(PCs)<-PCs$Row.names
ax_text<-list(
  family = "times",
  size = 12,
  color = "black")
t <- list(
  family = "times",
  size = 14,
  color = "black")
p <- plot_ly(PCs, x = ~PC1, y = ~PC2, z = ~PC3,
   marker = list(color = ~Treatment, 
                 colorscale = c('#FFE1A1', '#683531'), 
                 showscale = FALSE)) %>%
  add_markers() %>% 
  layout(scene = list(
     xaxis = list(title = 'PC1', zerolinewidth = 4, 
        zerolinecolor="darkgrey", linecolor="darkgrey", 
        linewidth=4, titlefont=t, tickfont=ax_text),
     yaxis = list(title = 'PC2', zerolinewidth = 4, 
        zerolinecolor="darkgrey", linecolor="darkgrey", 
        linewidth=4, titlefont=t, tickfont=ax_text),
    zaxis = list(title = 'PC3', zerolinewidth = 4, 
        zerolinecolor="darkgrey",  linecolor="darkgrey", 
        linewidth=4, titlefont=t, tickfont=ax_text)),
  annotations = list(
           x = 1.13,
           y = 1.03,
           text = 'Transgene',
           xref = '1',
           yref = '0',
           showarrow = FALSE))
p #must comment out for PDF generation via knitr (Pandoc)
<div id="htmlwidget-31e876b1dcf983ad8560" style="width:672px;height:480px;" class="plotly html-widget"></div>
<script type="application/json" data-for="htmlwidget-31e876b1dcf983ad8560">{"x":{"visdat":{"24163516c15f":["function () ","plotlyVisDat"]},"cur_data":"24163516c15f","attrs":{"24163516c15f":{"x":{},"y":{},"z":{},"marker":{"color":{},"colorscale":["#FFE1A1","#683531"],"showscale":false},"alpha_stroke":1,"sizes":[10,100],"spans":[1,20],"type":"scatter3d","mode":"markers","inherit":true}},"layout":{"margin":{"b":40,"l":60,"t":25,"r":10},"scene":{"xaxis":{"title":"PC1","zerolinewidth":4,"zerolinecolor":"darkgrey","linecolor":"darkgrey","linewidth":4,"titlefont":{"family":"times","size":14,"color":"black"},"tickfont":{"family":"times","size":12,"color":"black"}},"yaxis":{"title":"PC2","zerolinewidth":4,"zerolinecolor":"darkgrey","linecolor":"darkgrey","linewidth":4,"titlefont":{"family":"times","size":14,"color":"black"},"tickfont":{"family":"times","size":12,"color":"black"}},"zaxis":{"title":"PC3","zerolinewidth":4,"zerolinecolor":"darkgrey","linecolor":"darkgrey","linewidth":4,"titlefont":{"family":"times","size":14,"color":"black"},"tickfont":{"family":"times","size":12,"color":"black"}}},"annotations":[{"x":1.13,"y":1.03,"text":"Transgene","xref":"1","yref":"0","showarrow":false}],"hovermode":"closest","showlegend":false},"source":"A","config":{"showSendToCloud":false},"data":[{"x":[-80685.8062266134,-179159.155038288,-71174.6020569514,-98837.6818655239,107209.915862281,67172.1023848943,126782.66993385,64335.4461343561,57861.2685138884,6495.84235810865],"y":[23486.2585286078,-39290.1380681,29022.5261011266,-26215.9471145263,-6260.94379780434,-117205.227779094,-31131.4968746382,43324.0712417056,62823.1246480386,61447.7731146841],"z":[62003.199332036,8027.62969924111,-102319.112373534,19828.7311181967,4883.69474409674,-25376.6388502875,26310.5409484113,7892.67591266029,-29904.3191763238,28653.5986455029],"marker":{"color":[0,0,0,0,2,2,2,1,1,1],"colorscale":["#FFE1A1","#683531"],"showscale":false,"line":{"color":"rgba(31,119,180,1)"}},"type":"scatter3d","mode":"markers","error_y":{"color":"rgba(31,119,180,1)"},"error_x":{"color":"rgba(31,119,180,1)"},"line":{"color":"rgba(31,119,180,1)"},"frame":null}],"highlight":{"on":"plotly_click","persistent":false,"dynamic":false,"selectize":false,"opacityDim":0.2,"selected":{"opacity":1},"debounce":0},"shinyEvents":["plotly_hover","plotly_click","plotly_selected","plotly_relayout","plotly_brushed","plotly_brushing","plotly_clickannotation","plotly_doubleclick","plotly_deselect","plotly_afterplot","plotly_sunburstclick"],"base_url":"https://plot.ly"},"evals":[],"jsHooks":[]}</script>

2-D PCA

library(ggfortify)
library(cluster)
autoplot(pca.comp, data = data.pca_Final, colour = "Treatment")

Correlation of Differential Gene Expression

# Format for Correlation
library(corrplot)
library(Hmisc)
cor<-data.matrix((counts_p05))
cor.m<-rcorr(cor)
cor.r<-cor(cor)
paletteLength <- 100
myColor <- colorRampPalette(c("dodgerblue4", "white", "brown4"))(paletteLength)
p.mat<-cor.mtest(cor.r)$p
paletteLength <- 100
myColor <- colorRampPalette(c("black", "white","firebrick"))(paletteLength)
pheatmap(cor.r, 
         clustering_method = "single",
         cutree_rows = 3,
         cutree_cols = 3,
         cluster_cols=T,
         border_color=NA, 
         cluster_rows=T, 
         scale = "none", 
         show_colnames = F, 
         show_rownames = F, 
         color = myColor,
         annotation_col = Index)

miRNA-Sequencing Analysis

Data Pre-Processing

To determine the effect of miRNA, as well as identify the putative miRNA disregulated in a dose-dependent manner, miRNA-sequencing was performed on the same samples as before.

Count Normalization

DESeq2 (version 1.18.1) was used to perform the raw count normalization within R (version 3.4.2)

######### RUN DESeq2
dds_mir<-DESeqDataSetFromMatrix(countData=countData_mir, colData = colData_mir, design= ~Transgene)
dds_mir
## class: DESeqDataSet 
## dim: 623 9 
## metadata(1): version
## assays(1): counts
## rownames(623): mmu-miR-1929-5p mmu-miR-1930-5p ... mmu-miR-215-3p
##   mmu-miR-7236-3p
## rowData names(0):
## colnames(9): Counts_control0 Counts_control1 ... Counts_TGH1
##   Counts_TGH2
## colData names(3): Sample_ID Transgene Treatment
dds_mir$Transgene<-relevel(dds_mir$Transgene, ref = "NO") # setting the reference to wild-type genotype. only relevant for factors.
#Determine the Dispersion Relationship (determines which distribution to use for the differential analysis) - should take about 2 minutes
dds_mir <- estimateSizeFactors(dds_mir)
dds_mir <- estimateDispersions(dds_mir)
plotDispEsts(dds_mir)

There appears to be a linear negative correlation between the mean and dispersion estimates, so the parametric "Wald" model should be an appropriate fit for differential expression analysis. Furthermore, we could get away with the parametric fit-type, but the run-time is not significantly impaired, allowing us to use the 'local' fit-type. NOTE: If it were nonlinear throughout, we would require a 'local' nonparametric fit-type.

Differential Expression Analysis

##Pre-Filter to reduce the size of this dataset (according to the DESeq2 document reccomendations)
dds_mir <- dds_mir[ rowSums(counts(dds_mir)) > 1, ]
dds_mir
## class: DESeqDataSet 
## dim: 623 9 
## metadata(1): version
## assays(2): counts mu
## rownames(623): mmu-miR-1929-5p mmu-miR-1930-5p ... mmu-miR-215-3p
##   mmu-miR-7236-3p
## rowData names(10): baseMean baseVar ... dispOutlier dispMAP
## colnames(9): Counts_control0 Counts_control1 ... Counts_TGH1
##   Counts_TGH2
## colData names(4): Sample_ID Transgene Treatment sizeFactor
################Run DESeq2 differential quantification (Likelihood ratio test (LRT), instead of the wald test - easier for large datasets)
dds_mir<-DESeq(dds_mir, test="Wald", fitType="parametric")
#compile the results tables
res_mir<-DESeq2::results(dds_mir)
resdf_mir<-data.frame(res_mir)
resdf_mir$external_gene_name<-row.names(resdf_mir)
resdf_mir$ensembl_gene_id<-resdf_mir$external_gene_name

Once the differential Expression analysis was performed, the following were compiled into a results data matrix: Log2FoldChange, P-value, Bonferroni-Adjusted P-Value (Q-value), and normalized counts for each sample.

####Add normalized count data (for heatmap and sota)
normcount_mir<-counts(dds_mir)
normcount_mir<-as.data.frame(normcount_mir)
normcount_mir$ensembl_gene_id<-row.names(normcount_mir)
results_mir<-dplyr::left_join(resdf_mir, normcount_mir, by="ensembl_gene_id")
rownames(results_mir)<-results_mir$external_gene_name

QQ Plot

Before we examined the gene networks and pathways differentially regulated by NRF2 knockout, the first task was to determine whether transgene induction resulted in global changes. An effective way of determining this is the QQ plot, which compares the P-value distribution produced by the pairwise comparison (transgenic vs. WT mouse) to that of a random normal distribution. Below, it is evident that the two experimental groups produce robustly divergent expression patterns consistent with a true population difference worthy of differential expression analysis.

#Create Q-Q plot
results_mir<-results_mir[complete.cases(results_mir),]
write.csv(results_mir, "../2_Output/miRNA/results_miRNA_TG.v.NTG.csv")
pQQ(results_mir$pvalue, lim=c(0,10))

Heatmap Visualization of Transgenic vs. WT Comparison (P < 0.05)

In order to visualize the distribution of differentially expressed genes, as well as determine the effect of transgenic intensity (TGH vs. TGL), hierarchical clustering and heatmap visualization were performed at the Q < 0.05 statistical level. This analysis reveals that P < 0.05 is sufficient to separate all samples by genotype. In particular, it is apparent that the TGH group display more robust differential expression than TGL when compared to control, in a sort of dose-dependent manner.

library(pheatmap)
results_p05_mir<-filter(results_mir, padj<.01)
rownames(results_p05_mir)<-results_p05_mir$ensembl_gene_id
##Index file for annotating samples
rownames(colData_mir)<-colData_mir$Sample_ID
Index_mir<-dplyr::select(colData_mir, Transgene, Treatment)
Index_mir<-as.data.frame(Index_mir)
counts_p05_mir<-dplyr::select(results_p05_mir, Counts_control0:Counts_TGH2)

paletteLength <- 100
myColor <- colorRampPalette(c("dodgerblue4", "white", "gold2"))(paletteLength)
pheatmap(counts_p05_mir, 
         cluster_cols=T, 
         border_color=NA, 
         cluster_rows=T, 
         scale = 'row', 
         show_colnames = T, 
         show_rownames = T, 
         color = myColor,
         annotation_col = Index_mir)

Principal Components Analysis

Once we established that the populations under consideration truly display divergene expression patterns, we sought to determine whether unbiased global gene expression patterns recapitulate TGL versus TGH phenotypes within the transgenic group. To accomplish this, an unsupervised Principal Components Analysis (PCA) was initially used with normalized counts.

PCA Features

Before running the principal components analysis, it was necessary to first determine the number of PC's required to account for 80% of the variance, a machine-learning algorithmm benchmark that provides sufficient confidence in the analysis.

#Plot Features of the PCA
library(readxl)
library(dplyr)
library(plotly)
##Import the data to be used for PCA
results_dmir<-dplyr::select(results_mir, Counts_control0:Counts_TGH2)
results_dmir<-results_dmir[order(-rowSums(results_dmir)),]
#transpose the dataset (required for PCA)
data.pca_dmir<-t(results_dmir)
data.pca_dmir<-as.data.frame(data.pca_dmir)
##Import the data to be used for annotation
rownames(colData_mir)<-colData_mir$Sample_ID
Index_mir<-dplyr::select(colData_mir, Transgene, Treatment)
Index_mir<-as.data.frame(Index_mir)
##merge the file
data.pca_Final_dmir<-merge(Index_mir, data.pca_dmir, by=0)
rownames(data.pca_Final_dmir)<-data.pca_Final_dmir$Row.names
pca.comp_dmir<-prcomp(data.pca_Final_dmir[,(ncol(Index_mir)+2):ncol(data.pca_Final_dmir)])

pcaCharts=function(x) {
    x.var <- x$sdev ^ 2
    x.pvar <- x.var/sum(x.var)
    par(mfrow=c(2,2))
    plot(x.pvar,xlab="Principal component", 
         ylab="Proportion of variance", ylim=c(0,1), type='b')
    plot(cumsum(x.pvar),xlab="Principal component", 
         ylab="Cumulative Proportion of variance", 
         ylim=c(0,1), 
         type='b')
    screeplot(x)
    screeplot(x,type="l")
    par(mfrow=c(1,1))
}
pcaCharts(pca.comp_dmir)

3-Dimensional PCA of miRNA

From the previous calculations, it is seens that again only 2 principal components are necessary (accounting for >80% cumulative variance). Nonetheless, below is a 3-D PCA to ensure that all groups are characterize to higher-degree of stringency.

##Create a 3D-PCA for Inspection
PCs_mir<-merge(pca.comp_dmir$x, Index_mir, by=0)
rownames(PCs_mir)<-PCs_mir$Row.names
ax_text<-list(
  family = "times",
  size = 12,
  color = "black")
t <- list(
  family = "times",
  size = 14,
  color = "black")
p_mir <- plot_ly(PCs_mir, x = ~PC1, y = ~PC2, z = ~PC3,
   marker = list(color = ~Treatment, 
                 colorscale = c('#FFE1A1', '#683531'), 
                 showscale = TRUE)) %>%
  add_markers() %>% 
  layout(scene = list(
     xaxis = list(title = 'PC1', zerolinewidth = 4, 
        zerolinecolor="darkgrey", linecolor="darkgrey", 
        linewidth=4, titlefont=t, tickfont=ax_text),
     yaxis = list(title = 'PC2', zerolinewidth = 4, 
        zerolinecolor="darkgrey", linecolor="darkgrey", 
        linewidth=4, titlefont=t, tickfont=ax_text),
    zaxis = list(title = 'PC3', zerolinewidth = 4, 
        zerolinecolor="darkgrey",  linecolor="darkgrey", 
        linewidth=4, titlefont=t, tickfont=ax_text)),
  annotations = list(
           x = 1.13,
           y = 1.03,
           text = 'Transgene',
           xref = '1',
           yref = '0',
           showarrow = FALSE))
p_mir #must comment out for PDF generation via knitr (Pandoc)
<div id="htmlwidget-06f03b8417e95a29f241" style="width:672px;height:480px;" class="plotly html-widget"></div>
<script type="application/json" data-for="htmlwidget-06f03b8417e95a29f241">{"x":{"visdat":{"241669d94da1":["function () ","plotlyVisDat"]},"cur_data":"241669d94da1","attrs":{"241669d94da1":{"x":{},"y":{},"z":{},"marker":{"color":{},"colorscale":["#FFE1A1","#683531"],"showscale":true},"alpha_stroke":1,"sizes":[10,100],"spans":[1,20],"type":"scatter3d","mode":"markers","inherit":true}},"layout":{"margin":{"b":40,"l":60,"t":25,"r":10},"scene":{"xaxis":{"title":"PC1","zerolinewidth":4,"zerolinecolor":"darkgrey","linecolor":"darkgrey","linewidth":4,"titlefont":{"family":"times","size":14,"color":"black"},"tickfont":{"family":"times","size":12,"color":"black"}},"yaxis":{"title":"PC2","zerolinewidth":4,"zerolinecolor":"darkgrey","linecolor":"darkgrey","linewidth":4,"titlefont":{"family":"times","size":14,"color":"black"},"tickfont":{"family":"times","size":12,"color":"black"}},"zaxis":{"title":"PC3","zerolinewidth":4,"zerolinecolor":"darkgrey","linecolor":"darkgrey","linewidth":4,"titlefont":{"family":"times","size":14,"color":"black"},"tickfont":{"family":"times","size":12,"color":"black"}}},"annotations":[{"x":1.13,"y":1.03,"text":"Transgene","xref":"1","yref":"0","showarrow":false}],"hovermode":"closest","showlegend":false},"source":"A","config":{"showSendToCloud":false},"data":[{"x":[-364099.114849777,-27848.3270209532,685304.043075243,-306626.804485747,1042668.88413052,-1238285.56331604,135199.751481609,-111266.785230066,184953.91621521],"y":[-131098.197382159,-181984.00866072,-260451.615673919,140847.573845181,216038.02073061,9313.19811924191,104311.332558053,263336.513228046,-160312.816764333],"z":[220571.897722433,-71422.2706723823,56713.1727055869,-157348.735859851,-142619.069426904,-127041.807137686,190804.648758678,164776.726556951,-134434.562646827],"marker":{"color":[0,0,0,2,2,2,1,1,1],"colorscale":["#FFE1A1","#683531"],"showscale":true,"line":{"color":"rgba(31,119,180,1)"}},"type":"scatter3d","mode":"markers","error_y":{"color":"rgba(31,119,180,1)"},"error_x":{"color":"rgba(31,119,180,1)"},"line":{"color":"rgba(31,119,180,1)"},"frame":null}],"highlight":{"on":"plotly_click","persistent":false,"dynamic":false,"selectize":false,"opacityDim":0.2,"selected":{"opacity":1},"debounce":0},"shinyEvents":["plotly_hover","plotly_click","plotly_selected","plotly_relayout","plotly_brushed","plotly_brushing","plotly_clickannotation","plotly_doubleclick","plotly_deselect","plotly_afterplot","plotly_sunburstclick"],"base_url":"https://plot.ly"},"evals":[],"jsHooks":[]}</script>

2-D PCA

library(ggfortify)
library(cluster)
autoplot(pca.comp_dmir, data = data.pca_Final_dmir, colour = "Treatment")

Identifying Putative Nrf2 Binding Sites

In order to identify the response elements likely targeted by Nfe2l2 (Nrf2) we used the position-weighted matrix (PWM) generated by Brochley et al. We scanned the mus musculus genome (mm10) for all Nrf2 (Nfe2l2) response elements using the Nfe2l2 PWM via PWMScan (Ambrosini 2018); this process identified 80,756 Nrf2 response elements throughout the mouse genome. These genomic coordinates were then used to determine which differentially-expressed miRNA are likely under the control of Nrf2 based on the presents of Antioxidant Response Elements upstream of the miRNA coding region.

Nfe2l2 PWM (based on Brochley et al.) in Transfac format

AC MA0150.2
XX
ID Nfe2l2
XX DE MA0150.2 Nfe2l2 ; From JASPAR 2018
PO A C G T
01 278 23 103 6
02 0 2 0 408
03 0 0 400 10
04 410 0 0 0
05 14 287 74 35
06 52 11 11 336
07 26 315 30 39
08 329 2 47 32
09 3 3 404 0
10 3 398 6 3
11 346 13 15 36
XX
// \

Nfe2l2 response Element: Genomic Annotation

Once the Nfe2l2 response elements were identified, we used Hypergeometric Optimization for Motif Enrichment (HOMER) to annotate these genomic regions according to the most proximal gene. The following command was used: annotatePeaks pwmscan_mm10_40220_40766.bed mm10 > Nfe2l2_REs.Genome.txt.

Annotated Response Elements
PeakID..cmd.annotatePeaks.pl.pwmscan_mm10_40220_40766.bed.mm10. Chr Start End Strand Peak.Score Focus.Ratio.Region.Size Annotation Detailed.Annotation Distance.to.TSS Nearest.PromoterID Entrez.ID Nearest.Unigene Nearest.Refseq Nearest.Ensembl Gene.Name Gene.Alias Gene.Description Gene.Type
ATGACTCAGCA-1912 chr6 82702040 82702050 + 1959 Intergenic B2_Mm2|SINE|B2 -49180 NM_025882 66979 Mm.195753 NM_025882 ENSMUSG00000030042 Pole4 2400007P05Rik|5830430F06Rik polymerase (DNA-directed), epsilon 4 (p12 subunit) protein-coding
ATGACTCAGCA-4868 chr17 64662442 64662452 - 1959 intron (NM_008549, intron 6 of 21) B2_Mm2|SINE|B2 60798 NM_008549 17158 Mm.2433 NM_008549 ENSMUSG00000024085 Man2a1 Mana-2|Mana2|Map-2 mannosidase 2, alpha 1 protein-coding
ATGACTCAGCA-1928 chr6 87853595 87853605 + 1959 Intergenic Intergenic -2494 NM_001355195 12785 Mm.290251 NM_013493 ENSMUSG00000030057 Cnbp AA408710|Cnbp1|Znf9 cellular nucleic acid binding protein protein-coding
ATGACTCAGCA-405 chr1 191471513 191471523 - 1959 Intergenic RSINE1|SINE|B4 -6470 NR_151615 102634668 NR_151615 Gm32200 - predicted gene, 32200 ncRNA
ATGACTCAGCA-1617 chr5 100753629 100753639 + 1959 Intergenic MamSINE1|SINE|tRNA -33918 NM_152803 15442 Mm.265786 NM_152803 ENSMUSG00000035273 Hpse HSE1|Hpa|Hpr1 heparanase protein-coding
ATGACTCAGCA-4388 chr15 36657700 36657710 - 1959 Intergenic Intergenic -48732 NM_008774 18458 Mm.371570 NM_008774 ENSMUSG00000022283 Pabpc1 PABP|Pabp1|PabpI|Pabpl1|ePAB poly(A) binding protein, cytoplasmic 1 protein-coding

miRNA with Proximal Nrf2 Response Elements

We then inspected the list of miRNA that were only differentially-expressed in the Dose Effect (TgH vs. TgL, excluding Tg vs. NTg). From this, we found that 20 of the 40 differentially-expressed miRNA contained at least 1 Nrf2 response element in the most-proximal promoter region.

Determine predicted miRNA Targets

## Searching diana_microt ...
## Searching elmmo ...
## Searching microcosm ...
## Searching miranda ...
## Searching mirdb ...
## Searching pictar ...
## Searching pita ...
## Searching targetscan ...

miRNA-mRNA Network Analysis

The next component of this analysis was to determine whether upstream miRNA have overlapping predicted downstream mRNA targets. To accomplish this aim, a bipartite network analysis was created to depict (1) the differentially-expressed miRNA containing a proximal upstream Nrf2 response element, and (2) their downstream predicted mRNA targets identified via multiMiR.

Supplemental Table: R Session Information

All packages and setting are acquired using the following command:

##  setting  value                       
##  version  R version 4.0.3 (2020-10-10)
##  os       macOS Big Sur 10.16         
##  system   x86_64, darwin17.0          
##  ui       X11                         
##  language (EN)                        
##  collate  en_US.UTF-8                 
##  ctype    en_US.UTF-8                 
##  tz       Europe/Berlin               
##  date     2021-02-12
Packages and Required Dependencies
package ondiskversion loadedversion path loadedpath attached is_base date source md5ok library
annotate annotate 1.68.0 1.68.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/annotate /Library/Frameworks/R.framework/Versions/4.0/Resources/library/annotate FALSE FALSE 2020-10-27 Bioconductor /Library/Frameworks/R.framework/Versions/4.0/Resources/library
AnnotationDbi AnnotationDbi 1.52.0 1.52.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/AnnotationDbi /Library/Frameworks/R.framework/Versions/4.0/Resources/library/AnnotationDbi FALSE FALSE 2020-10-27 Bioconductor /Library/Frameworks/R.framework/Versions/4.0/Resources/library
askpass askpass 1.1 1.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/askpass /Library/Frameworks/R.framework/Versions/4.0/Resources/library/askpass FALSE FALSE 2019-01-13 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
assertthat assertthat 0.2.1 0.2.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/assertthat /Library/Frameworks/R.framework/Versions/4.0/Resources/library/assertthat FALSE FALSE 2019-03-21 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
backports backports 1.2.1 1.2.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/backports /Library/Frameworks/R.framework/Versions/4.0/Resources/library/backports FALSE FALSE 2020-12-09 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
base64enc base64enc 0.1.3 0.1-3 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/base64enc /Library/Frameworks/R.framework/Versions/4.0/Resources/library/base64enc FALSE FALSE 2015-07-28 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
Biobase Biobase 2.50.0 2.50.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/Biobase /Library/Frameworks/R.framework/Versions/4.0/Resources/library/Biobase TRUE FALSE 2020-10-27 Bioconductor /Library/Frameworks/R.framework/Versions/4.0/Resources/library
BiocFileCache BiocFileCache 1.14.0 1.14.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/BiocFileCache /Library/Frameworks/R.framework/Versions/4.0/Resources/library/BiocFileCache FALSE FALSE 2020-10-27 Bioconductor /Library/Frameworks/R.framework/Versions/4.0/Resources/library
BiocGenerics BiocGenerics 0.36.0 0.36.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/BiocGenerics /Library/Frameworks/R.framework/Versions/4.0/Resources/library/BiocGenerics TRUE FALSE 2020-10-27 Bioconductor /Library/Frameworks/R.framework/Versions/4.0/Resources/library
BiocManager BiocManager 1.30.10 1.30.10 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/BiocManager /Library/Frameworks/R.framework/Versions/4.0/Resources/library/BiocManager TRUE FALSE 2019-11-16 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
BiocParallel BiocParallel 1.24.1 1.24.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/BiocParallel /Library/Frameworks/R.framework/Versions/4.0/Resources/library/BiocParallel FALSE FALSE 2020-11-06 Bioconductor /Library/Frameworks/R.framework/Versions/4.0/Resources/library
biomaRt biomaRt 2.46.3 2.46.3 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/biomaRt /Library/Frameworks/R.framework/Versions/4.0/Resources/library/biomaRt TRUE FALSE 2021-02-09 Bioconductor /Library/Frameworks/R.framework/Versions/4.0/Resources/library
bipartite bipartite 2.16 2.16 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/bipartite /Library/Frameworks/R.framework/Versions/4.0/Resources/library/bipartite TRUE FALSE 2021-02-04 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
bit bit 4.0.4 4.0.4 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/bit /Library/Frameworks/R.framework/Versions/4.0/Resources/library/bit FALSE FALSE 2020-08-04 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
bit64 bit64 4.0.5 4.0.5 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/bit64 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/bit64 FALSE FALSE 2020-08-30 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
bitops bitops 1.0.6 1.0-6 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/bitops /Library/Frameworks/R.framework/Versions/4.0/Resources/library/bitops FALSE FALSE 2013-08-17 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
blob blob 1.2.1 1.2.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/blob /Library/Frameworks/R.framework/Versions/4.0/Resources/library/blob FALSE FALSE 2020-01-20 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
cachem cachem 1.0.3 1.0.3 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/cachem /Library/Frameworks/R.framework/Versions/4.0/Resources/library/cachem FALSE FALSE 2021-02-04 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
calibrate calibrate 1.7.7 1.7.7 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/calibrate /Library/Frameworks/R.framework/Versions/4.0/Resources/library/calibrate TRUE FALSE 2020-06-19 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
callr callr 3.5.1 3.5.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/callr /Library/Frameworks/R.framework/Versions/4.0/Resources/library/callr FALSE FALSE 2020-10-13 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
cellranger cellranger 1.1.0 1.1.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/cellranger /Library/Frameworks/R.framework/Versions/4.0/Resources/library/cellranger FALSE FALSE 2016-07-27 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
checkmate checkmate 2.0.0 2.0.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/checkmate /Library/Frameworks/R.framework/Versions/4.0/Resources/library/checkmate FALSE FALSE 2020-02-06 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
cli cli 2.3.0 2.3.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/cli /Library/Frameworks/R.framework/Versions/4.0/Resources/library/cli FALSE FALSE 2021-01-31 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
cluster cluster 2.1.0 2.1.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/cluster /Library/Frameworks/R.framework/Versions/4.0/Resources/library/cluster TRUE FALSE 2019-06-19 CRAN (R 4.0.3) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
coda coda 0.19.4 0.19-4 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/coda /Library/Frameworks/R.framework/Versions/4.0/Resources/library/coda FALSE FALSE 2020-09-30 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
codetools codetools 0.2.18 0.2-18 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/codetools /Library/Frameworks/R.framework/Versions/4.0/Resources/library/codetools FALSE FALSE 2020-11-04 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
colorspace colorspace 2.0.0 2.0-0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/colorspace /Library/Frameworks/R.framework/Versions/4.0/Resources/library/colorspace FALSE FALSE 2020-11-11 CRAN (R 4.0.3) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
corrplot corrplot 0.84 0.84 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/corrplot /Library/Frameworks/R.framework/Versions/4.0/Resources/library/corrplot TRUE FALSE 2017-10-16 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
crayon crayon 1.4.1 1.4.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/crayon /Library/Frameworks/R.framework/Versions/4.0/Resources/library/crayon FALSE FALSE 2021-02-08 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
crosstalk crosstalk 1.1.1 1.1.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/crosstalk /Library/Frameworks/R.framework/Versions/4.0/Resources/library/crosstalk FALSE FALSE 2021-01-12 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
curl curl 4.3 4.3 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/curl /Library/Frameworks/R.framework/Versions/4.0/Resources/library/curl FALSE FALSE 2019-12-02 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
data.table data.table 1.13.6 1.13.6 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/data.table /Library/Frameworks/R.framework/Versions/4.0/Resources/library/data.table TRUE FALSE 2020-12-30 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
DBI DBI 1.1.1 1.1.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/DBI /Library/Frameworks/R.framework/Versions/4.0/Resources/library/DBI FALSE FALSE 2021-01-15 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
dbplyr dbplyr 2.1.0 2.1.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/dbplyr /Library/Frameworks/R.framework/Versions/4.0/Resources/library/dbplyr FALSE FALSE 2021-02-03 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
DelayedArray DelayedArray 0.16.1 0.16.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/DelayedArray /Library/Frameworks/R.framework/Versions/4.0/Resources/library/DelayedArray FALSE FALSE 2021-01-22 Bioconductor /Library/Frameworks/R.framework/Versions/4.0/Resources/library
desc desc 1.2.0 1.2.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/desc /Library/Frameworks/R.framework/Versions/4.0/Resources/library/desc FALSE FALSE 2018-05-01 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
DESeq2 DESeq2 1.30.0 1.30.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/DESeq2 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/DESeq2 TRUE FALSE 2020-10-27 Bioconductor /Library/Frameworks/R.framework/Versions/4.0/Resources/library
devtools devtools 2.3.2 2.3.2 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/devtools /Library/Frameworks/R.framework/Versions/4.0/Resources/library/devtools FALSE FALSE 2020-09-18 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
digest digest 0.6.27 0.6.27 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/digest /Library/Frameworks/R.framework/Versions/4.0/Resources/library/digest FALSE FALSE 2020-10-24 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
dotCall64 dotCall64 1.0.0 1.0-0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/dotCall64 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/dotCall64 FALSE FALSE 2018-07-30 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
dplyr dplyr 1.0.4 1.0.4 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/dplyr /Library/Frameworks/R.framework/Versions/4.0/Resources/library/dplyr TRUE FALSE 2021-02-02 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
ellipsis ellipsis 0.3.1 0.3.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/ellipsis /Library/Frameworks/R.framework/Versions/4.0/Resources/library/ellipsis FALSE FALSE 2020-05-15 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
evaluate evaluate 0.14 0.14 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/evaluate /Library/Frameworks/R.framework/Versions/4.0/Resources/library/evaluate FALSE FALSE 2019-05-28 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
farver farver 2.0.3 2.0.3 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/farver /Library/Frameworks/R.framework/Versions/4.0/Resources/library/farver FALSE FALSE 2020-01-16 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
fastmap fastmap 1.1.0 1.1.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/fastmap /Library/Frameworks/R.framework/Versions/4.0/Resources/library/fastmap FALSE FALSE 2021-01-25 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
ff ff 4.0.4 4.0.4 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/ff /Library/Frameworks/R.framework/Versions/4.0/Resources/library/ff FALSE FALSE 2020-10-13 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
fields fields 11.6 11.6 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/fields /Library/Frameworks/R.framework/Versions/4.0/Resources/library/fields FALSE FALSE 2020-10-09 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
foreign foreign 0.8.81 0.8-81 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/foreign /Library/Frameworks/R.framework/Versions/4.0/Resources/library/foreign FALSE FALSE 2020-12-22 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
Formula Formula 1.2.4 1.2-4 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/Formula /Library/Frameworks/R.framework/Versions/4.0/Resources/library/Formula TRUE FALSE 2020-10-16 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
fs fs 1.5.0 1.5.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/fs /Library/Frameworks/R.framework/Versions/4.0/Resources/library/fs FALSE FALSE 2020-07-31 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
genefilter genefilter 1.72.1 1.72.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/genefilter /Library/Frameworks/R.framework/Versions/4.0/Resources/library/genefilter FALSE FALSE 2021-01-21 Bioconductor /Library/Frameworks/R.framework/Versions/4.0/Resources/library
geneplotter geneplotter 1.68.0 1.68.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/geneplotter /Library/Frameworks/R.framework/Versions/4.0/Resources/library/geneplotter FALSE FALSE 2020-10-27 Bioconductor /Library/Frameworks/R.framework/Versions/4.0/Resources/library
generics generics 0.1.0 0.1.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/generics /Library/Frameworks/R.framework/Versions/4.0/Resources/library/generics FALSE FALSE 2020-10-31 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
GenomeInfoDb GenomeInfoDb 1.26.2 1.26.2 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/GenomeInfoDb /Library/Frameworks/R.framework/Versions/4.0/Resources/library/GenomeInfoDb TRUE FALSE 2020-12-08 Bioconductor /Library/Frameworks/R.framework/Versions/4.0/Resources/library
GenomeInfoDbData GenomeInfoDbData 1.2.4 1.2.4 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/GenomeInfoDbData /Library/Frameworks/R.framework/Versions/4.0/Resources/library/GenomeInfoDbData FALSE FALSE 2020-11-16 Bioconductor /Library/Frameworks/R.framework/Versions/4.0/Resources/library
GenomicRanges GenomicRanges 1.42.0 1.42.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/GenomicRanges /Library/Frameworks/R.framework/Versions/4.0/Resources/library/GenomicRanges TRUE FALSE 2020-10-27 Bioconductor /Library/Frameworks/R.framework/Versions/4.0/Resources/library
ggfortify ggfortify 0.4.11 0.4.11 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/ggfortify /Library/Frameworks/R.framework/Versions/4.0/Resources/library/ggfortify TRUE FALSE 2020-10-02 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
ggplot2 ggplot2 3.3.3 3.3.3 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/ggplot2 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/ggplot2 TRUE FALSE 2020-12-30 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
glue glue 1.4.2 1.4.2 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/glue /Library/Frameworks/R.framework/Versions/4.0/Resources/library/glue FALSE FALSE 2020-08-27 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
gridExtra gridExtra 2.3 2.3 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/gridExtra /Library/Frameworks/R.framework/Versions/4.0/Resources/library/gridExtra FALSE FALSE 2017-09-09 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
gtable gtable 0.3.0 0.3.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/gtable /Library/Frameworks/R.framework/Versions/4.0/Resources/library/gtable FALSE FALSE 2019-03-25 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
Haplin Haplin 7.2.3 7.2.3 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/Haplin /Library/Frameworks/R.framework/Versions/4.0/Resources/library/Haplin TRUE FALSE 2020-09-07 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
highr highr 0.8 0.8 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/highr /Library/Frameworks/R.framework/Versions/4.0/Resources/library/highr FALSE FALSE 2019-03-20 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
Hmisc Hmisc 4.4.2 4.4-2 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/Hmisc /Library/Frameworks/R.framework/Versions/4.0/Resources/library/Hmisc TRUE FALSE 2020-11-29 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
hms hms 1.0.0 1.0.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/hms /Library/Frameworks/R.framework/Versions/4.0/Resources/library/hms FALSE FALSE 2021-01-13 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
htmlTable htmlTable 2.1.0 2.1.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/htmlTable /Library/Frameworks/R.framework/Versions/4.0/Resources/library/htmlTable FALSE FALSE 2020-09-16 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
htmltools htmltools 0.5.1.1 0.5.1.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/htmltools /Library/Frameworks/R.framework/Versions/4.0/Resources/library/htmltools FALSE FALSE 2021-01-22 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
htmlwidgets htmlwidgets 1.5.3 1.5.3 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/htmlwidgets /Library/Frameworks/R.framework/Versions/4.0/Resources/library/htmlwidgets FALSE FALSE 2020-12-10 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
httr httr 1.4.2 1.4.2 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/httr /Library/Frameworks/R.framework/Versions/4.0/Resources/library/httr FALSE FALSE 2020-07-20 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
igraph igraph 1.2.6 1.2.6 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/igraph /Library/Frameworks/R.framework/Versions/4.0/Resources/library/igraph FALSE FALSE 2020-10-06 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
IRanges IRanges 2.24.1 2.24.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/IRanges /Library/Frameworks/R.framework/Versions/4.0/Resources/library/IRanges TRUE FALSE 2020-12-12 Bioconductor /Library/Frameworks/R.framework/Versions/4.0/Resources/library
jpeg jpeg 0.1.8.1 0.1-8.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/jpeg /Library/Frameworks/R.framework/Versions/4.0/Resources/library/jpeg FALSE FALSE 2019-10-24 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
jsonlite jsonlite 1.7.2 1.7.2 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/jsonlite /Library/Frameworks/R.framework/Versions/4.0/Resources/library/jsonlite FALSE FALSE 2020-12-09 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
kableExtra kableExtra 1.3.1 1.3.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/kableExtra /Library/Frameworks/R.framework/Versions/4.0/Resources/library/kableExtra TRUE FALSE 2020-10-22 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
knitr knitr 1.31 1.31 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/knitr /Library/Frameworks/R.framework/Versions/4.0/Resources/library/knitr TRUE FALSE 2021-01-27 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
labeling labeling 0.4.2 0.4.2 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/labeling /Library/Frameworks/R.framework/Versions/4.0/Resources/library/labeling FALSE FALSE 2020-10-20 CRAN (R 4.0.3) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
lattice lattice 0.20.41 0.20-41 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/lattice /Library/Frameworks/R.framework/Versions/4.0/Resources/library/lattice TRUE FALSE 2020-04-02 CRAN (R 4.0.3) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
latticeExtra latticeExtra 0.6.29 0.6-29 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/latticeExtra /Library/Frameworks/R.framework/Versions/4.0/Resources/library/latticeExtra FALSE FALSE 2019-12-19 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
lazyeval lazyeval 0.2.2 0.2.2 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/lazyeval /Library/Frameworks/R.framework/Versions/4.0/Resources/library/lazyeval FALSE FALSE 2019-03-15 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
lifecycle lifecycle 0.2.0 0.2.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/lifecycle /Library/Frameworks/R.framework/Versions/4.0/Resources/library/lifecycle FALSE FALSE 2020-03-06 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
locfit locfit 1.5.9.4 1.5-9.4 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/locfit /Library/Frameworks/R.framework/Versions/4.0/Resources/library/locfit FALSE FALSE 2020-03-25 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
magrittr magrittr 2.0.1 2.0.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/magrittr /Library/Frameworks/R.framework/Versions/4.0/Resources/library/magrittr FALSE FALSE 2020-11-17 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
maps maps 3.3.0 3.3.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/maps /Library/Frameworks/R.framework/Versions/4.0/Resources/library/maps FALSE FALSE 2018-04-03 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
MASS MASS 7.3.53 7.3-53 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/MASS /Library/Frameworks/R.framework/Versions/4.0/Resources/library/MASS TRUE FALSE 2020-09-09 CRAN (R 4.0.3) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
Matrix Matrix 1.3.2 1.3-2 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/Matrix /Library/Frameworks/R.framework/Versions/4.0/Resources/library/Matrix FALSE FALSE 2021-01-06 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
MatrixGenerics MatrixGenerics 1.2.1 1.2.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/MatrixGenerics /Library/Frameworks/R.framework/Versions/4.0/Resources/library/MatrixGenerics TRUE FALSE 2021-01-30 Bioconductor /Library/Frameworks/R.framework/Versions/4.0/Resources/library
matrixStats matrixStats 0.58.0 0.58.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/matrixStats /Library/Frameworks/R.framework/Versions/4.0/Resources/library/matrixStats TRUE FALSE 2021-01-29 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
memoise memoise 2.0.0 2.0.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/memoise /Library/Frameworks/R.framework/Versions/4.0/Resources/library/memoise FALSE FALSE 2021-01-26 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
mgcv mgcv 1.8.33 1.8-33 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/mgcv /Library/Frameworks/R.framework/Versions/4.0/Resources/library/mgcv FALSE FALSE 2020-08-27 CRAN (R 4.0.3) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
multiMiR multiMiR 1.12.0 1.12.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/multiMiR /Library/Frameworks/R.framework/Versions/4.0/Resources/library/multiMiR TRUE FALSE 2020-10-27 Bioconductor /Library/Frameworks/R.framework/Versions/4.0/Resources/library
munsell munsell 0.5.0 0.5.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/munsell /Library/Frameworks/R.framework/Versions/4.0/Resources/library/munsell FALSE FALSE 2018-06-12 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
network network 1.16.1 1.16.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/network /Library/Frameworks/R.framework/Versions/4.0/Resources/library/network TRUE FALSE 2020-10-07 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
nlme nlme 3.1.152 3.1-152 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/nlme /Library/Frameworks/R.framework/Versions/4.0/Resources/library/nlme FALSE FALSE 2021-02-04 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
nnet nnet 7.3.15 7.3-15 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/nnet /Library/Frameworks/R.framework/Versions/4.0/Resources/library/nnet FALSE FALSE 2021-01-24 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
openssl openssl 1.4.3 1.4.3 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/openssl /Library/Frameworks/R.framework/Versions/4.0/Resources/library/openssl FALSE FALSE 2020-09-18 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
permute permute 0.9.5 0.9-5 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/permute /Library/Frameworks/R.framework/Versions/4.0/Resources/library/permute TRUE FALSE 2019-03-12 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
pheatmap pheatmap 1.0.12 1.0.12 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/pheatmap /Library/Frameworks/R.framework/Versions/4.0/Resources/library/pheatmap TRUE FALSE 2019-01-04 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
pillar pillar 1.4.7 1.4.7 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/pillar /Library/Frameworks/R.framework/Versions/4.0/Resources/library/pillar FALSE FALSE 2020-11-20 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
pkgbuild pkgbuild 1.2.0 1.2.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/pkgbuild /Library/Frameworks/R.framework/Versions/4.0/Resources/library/pkgbuild FALSE FALSE 2020-12-15 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
pkgconfig pkgconfig 2.0.3 2.0.3 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/pkgconfig /Library/Frameworks/R.framework/Versions/4.0/Resources/library/pkgconfig FALSE FALSE 2019-09-22 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
pkgload pkgload 1.1.0 1.1.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/pkgload /Library/Frameworks/R.framework/Versions/4.0/Resources/library/pkgload FALSE FALSE 2020-05-29 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
plotly plotly 4.9.3 4.9.3 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/plotly /Library/Frameworks/R.framework/Versions/4.0/Resources/library/plotly TRUE FALSE 2021-01-10 CRAN (R 4.0.3) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
png png 0.1.7 0.1-7 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/png /Library/Frameworks/R.framework/Versions/4.0/Resources/library/png FALSE FALSE 2013-12-03 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
prettyunits prettyunits 1.1.1 1.1.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/prettyunits /Library/Frameworks/R.framework/Versions/4.0/Resources/library/prettyunits FALSE FALSE 2020-01-24 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
processx processx 3.4.5 3.4.5 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/processx /Library/Frameworks/R.framework/Versions/4.0/Resources/library/processx FALSE FALSE 2020-11-30 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
progress progress 1.2.2 1.2.2 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/progress /Library/Frameworks/R.framework/Versions/4.0/Resources/library/progress FALSE FALSE 2019-05-16 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
ps ps 1.5.0 1.5.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/ps /Library/Frameworks/R.framework/Versions/4.0/Resources/library/ps FALSE FALSE 2020-12-05 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
purrr purrr 0.3.4 0.3.4 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/purrr /Library/Frameworks/R.framework/Versions/4.0/Resources/library/purrr FALSE FALSE 2020-04-17 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
R6 R6 2.5.0 2.5.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/R6 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/R6 FALSE FALSE 2020-10-28 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
rappdirs rappdirs 0.3.3 0.3.3 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/rappdirs /Library/Frameworks/R.framework/Versions/4.0/Resources/library/rappdirs FALSE FALSE 2021-01-31 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
RColorBrewer RColorBrewer 1.1.2 1.1-2 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/RColorBrewer /Library/Frameworks/R.framework/Versions/4.0/Resources/library/RColorBrewer TRUE FALSE 2014-12-07 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
Rcpp Rcpp 1.0.6 1.0.6 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/Rcpp /Library/Frameworks/R.framework/Versions/4.0/Resources/library/Rcpp FALSE FALSE 2021-01-15 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
RCurl RCurl 1.98.1.2 1.98-1.2 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/RCurl /Library/Frameworks/R.framework/Versions/4.0/Resources/library/RCurl FALSE FALSE 2020-04-18 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
readxl readxl 1.3.1 1.3.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/readxl /Library/Frameworks/R.framework/Versions/4.0/Resources/library/readxl TRUE FALSE 2019-03-13 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
remotes remotes 2.2.0 2.2.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/remotes /Library/Frameworks/R.framework/Versions/4.0/Resources/library/remotes FALSE FALSE 2020-07-21 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
rlang rlang 0.4.10 0.4.10 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/rlang /Library/Frameworks/R.framework/Versions/4.0/Resources/library/rlang FALSE FALSE 2020-12-30 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
rle rle 0.9.2 0.9.2 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/rle /Library/Frameworks/R.framework/Versions/4.0/Resources/library/rle FALSE FALSE 2020-09-25 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
rmarkdown rmarkdown 2.6 2.6 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/rmarkdown /Library/Frameworks/R.framework/Versions/4.0/Resources/library/rmarkdown FALSE FALSE 2020-12-14 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
rpart rpart 4.1.15 4.1-15 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/rpart /Library/Frameworks/R.framework/Versions/4.0/Resources/library/rpart FALSE FALSE 2019-04-12 CRAN (R 4.0.3) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
rprojroot rprojroot 2.0.2 2.0.2 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/rprojroot /Library/Frameworks/R.framework/Versions/4.0/Resources/library/rprojroot FALSE FALSE 2020-11-15 CRAN (R 4.0.3) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
RSQLite RSQLite 2.2.3 2.2.3 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/RSQLite /Library/Frameworks/R.framework/Versions/4.0/Resources/library/RSQLite FALSE FALSE 2021-01-24 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
rstudioapi rstudioapi 0.13 0.13 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/rstudioapi /Library/Frameworks/R.framework/Versions/4.0/Resources/library/rstudioapi FALSE FALSE 2020-11-12 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
rvest rvest 0.3.6 0.3.6 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/rvest /Library/Frameworks/R.framework/Versions/4.0/Resources/library/rvest FALSE FALSE 2020-07-25 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
S4Vectors S4Vectors 0.28.1 0.28.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/S4Vectors /Library/Frameworks/R.framework/Versions/4.0/Resources/library/S4Vectors TRUE FALSE 2020-12-09 Bioconductor /Library/Frameworks/R.framework/Versions/4.0/Resources/library
scales scales 1.1.1 1.1.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/scales /Library/Frameworks/R.framework/Versions/4.0/Resources/library/scales FALSE FALSE 2020-05-11 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
sessioninfo sessioninfo 1.1.1 1.1.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/sessioninfo /Library/Frameworks/R.framework/Versions/4.0/Resources/library/sessioninfo FALSE FALSE 2018-11-05 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
sna sna 2.6 2.6 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/sna /Library/Frameworks/R.framework/Versions/4.0/Resources/library/sna TRUE FALSE 2020-10-06 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
spam spam 2.6.0 2.6-0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/spam /Library/Frameworks/R.framework/Versions/4.0/Resources/library/spam FALSE FALSE 2020-12-14 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
statnet.common statnet.common 4.4.1 4.4.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/statnet.common /Library/Frameworks/R.framework/Versions/4.0/Resources/library/statnet.common TRUE FALSE 2020-10-03 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
stringi stringi 1.5.3 1.5.3 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/stringi /Library/Frameworks/R.framework/Versions/4.0/Resources/library/stringi FALSE FALSE 2020-09-09 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
stringr stringr 1.4.0 1.4.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/stringr /Library/Frameworks/R.framework/Versions/4.0/Resources/library/stringr FALSE FALSE 2019-02-10 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
SummarizedExperiment SummarizedExperiment 1.20.0 1.20.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/SummarizedExperiment /Library/Frameworks/R.framework/Versions/4.0/Resources/library/SummarizedExperiment TRUE FALSE 2020-10-27 Bioconductor /Library/Frameworks/R.framework/Versions/4.0/Resources/library
survival survival 3.2.7 3.2-7 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/survival /Library/Frameworks/R.framework/Versions/4.0/Resources/library/survival TRUE FALSE 2020-09-28 CRAN (R 4.0.3) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
testthat testthat 3.0.1 3.0.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/testthat /Library/Frameworks/R.framework/Versions/4.0/Resources/library/testthat FALSE FALSE 2020-12-17 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
tibble tibble 3.0.6 3.0.6 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/tibble /Library/Frameworks/R.framework/Versions/4.0/Resources/library/tibble FALSE FALSE 2021-01-29 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
tidyr tidyr 1.1.2 1.1.2 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/tidyr /Library/Frameworks/R.framework/Versions/4.0/Resources/library/tidyr FALSE FALSE 2020-08-27 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
tidyselect tidyselect 1.1.0 1.1.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/tidyselect /Library/Frameworks/R.framework/Versions/4.0/Resources/library/tidyselect FALSE FALSE 2020-05-11 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
usethis usethis 2.0.1 2.0.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/usethis /Library/Frameworks/R.framework/Versions/4.0/Resources/library/usethis FALSE FALSE 2021-02-10 CRAN (R 4.0.3) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
vctrs vctrs 0.3.6 0.3.6 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/vctrs /Library/Frameworks/R.framework/Versions/4.0/Resources/library/vctrs FALSE FALSE 2020-12-17 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
vegan vegan 2.5.7 2.5-7 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/vegan /Library/Frameworks/R.framework/Versions/4.0/Resources/library/vegan TRUE FALSE 2020-11-28 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
viridisLite viridisLite 0.3.0 0.3.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/viridisLite /Library/Frameworks/R.framework/Versions/4.0/Resources/library/viridisLite FALSE FALSE 2018-02-01 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
webshot webshot 0.5.2 0.5.2 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/webshot /Library/Frameworks/R.framework/Versions/4.0/Resources/library/webshot FALSE FALSE 2019-11-22 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
withr withr 2.4.1 2.4.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/withr /Library/Frameworks/R.framework/Versions/4.0/Resources/library/withr FALSE FALSE 2021-01-26 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
xfun xfun 0.20 0.20 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/xfun /Library/Frameworks/R.framework/Versions/4.0/Resources/library/xfun FALSE FALSE 2021-01-06 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
XML XML 3.99.0.5 3.99-0.5 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/XML /Library/Frameworks/R.framework/Versions/4.0/Resources/library/XML FALSE FALSE 2020-07-23 CRAN (R 4.0.2) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
xml2 xml2 1.3.2 1.3.2 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/xml2 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/xml2 FALSE FALSE 2020-04-23 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
xtable xtable 1.8.4 1.8-4 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/xtable /Library/Frameworks/R.framework/Versions/4.0/Resources/library/xtable FALSE FALSE 2019-04-21 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
XVector XVector 0.30.0 0.30.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/XVector /Library/Frameworks/R.framework/Versions/4.0/Resources/library/XVector FALSE FALSE 2020-10-28 Bioconductor /Library/Frameworks/R.framework/Versions/4.0/Resources/library
yaml yaml 2.2.1 2.2.1 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/yaml /Library/Frameworks/R.framework/Versions/4.0/Resources/library/yaml FALSE FALSE 2020-02-01 CRAN (R 4.0.0) /Library/Frameworks/R.framework/Versions/4.0/Resources/library
zlibbioc zlibbioc 1.36.0 1.36.0 /Library/Frameworks/R.framework/Versions/4.0/Resources/library/zlibbioc /Library/Frameworks/R.framework/Versions/4.0/Resources/library/zlibbioc FALSE FALSE 2020-10-28 Bioconductor /Library/Frameworks/R.framework/Versions/4.0/Resources/library

About

No description, website, or topics provided.

Resources

Stars

Watchers

Forks

Releases

No releases published

Packages

 
 
 

Languages