Introduction and Data files

This dataset contains nine tissues (heart, hippocampus, hypothalamus, kidney, liver, prefrontal cortex, skeletal muscle, small intestine, and spleen) from C57BL/6J mice that were fed 2-deoxyglucose (6g/L) through their drinking water for 96hrs or 4wks. 96hr mice were given their 2DG treatment 2 weeks after the other cohort started the 4 week treatment. The organs from the mice were harvested and processed for metabolomics and transcriptomics. The data in this document pertains to the transcriptomics data only. The counts that were used were FPKM normalized before being log transformed. It was determined that sample A113 had low RNAseq quality and through further analyses with PCA, MA plots, and clustering was an outlier and will be removed for the rest of the analyses performed. This document will look at modules that were significantly correlated with traits and had pathways identified within the WGCNA. Those modules will be assessed to see which modules from other tissues and their modules significantly overlapped.

Load in Packages and read in files

needed.packages <- c("tidyverse", "here", "functional", "gplots", "dplyr", "GeneOverlap", "R.utils", "reshape2","magrittr","data.table", "RColorBrewer","preprocessCore", "ARTool","emmeans", "phia", "gprofiler2", "rlist")
for(i in 1:length(needed.packages)){library(needed.packages[i], character.only = TRUE)}

source(here("source_files","WGCNA_source.R"))
Matched<-readRDS(here("Data","Chang_2DG_BL6_Matched_annotation_intersection_modules.RData"))

Tissue

Each tissue module was compared to the traits in the experiment. The modules that were significantly correlated for a trait were then compared within the jaccard index across all other tissues. The significant overlaps were then summarized to determine which pathways were most common. Below are the pathway lists and their frequency for each module within a tissue that was also correlated to a trait and their frequency bar plots.

Heart

Darkgreen

genes.heart.darkgreen <- genes.jaccard.pathways(Matched, "Heart_darkgreen")

Pathway Table

if(is.null(genes.heart.darkgreen)) {
    print("No significant pathways")
  } else {genes.heart.darkgreen <- genes.heart.darkgreen$result
  DT.table.jaccard(genes.heart.darkgreen[c(11,4:6,3)])
  
 }

Darkgrey

genes.heart.darkgrey <- genes.jaccard.pathways(Matched, "Heart_darkgrey")

Pathway Table

if(is.null(genes.heart.darkgrey)) {
    print("No significant pathways")
  } else {genes.heart.darkgrey <- genes.heart.darkgrey$result
  DT.table.jaccard(genes.heart.darkgrey[c(11,4:6,3)])
  
 }

Darkorange

genes.heart.darkorange <- genes.jaccard.pathways(Matched, "Heart_darkorange")

Pathway Table

if(is.null(genes.heart.darkorange)) {
    print("No significant pathways")
  } else {genes.heart.darkorange <- genes.heart.darkorange$result
  DT.table.jaccard(genes.heart.darkorange[c(11,4:6,3)])
  
 }
## [1] "No significant pathways"

Plum1

Server won’t run this module currently

#genes.heart.plum1 <- genes.jaccard.pathways(Matched, "Heart_plum1")

Pathway Table

# if(is.null(genes.heart.plum1)) {
#     print("No significant pathways")
#   } else {genes.heart.plum1 <- genes.heart.plum1$result
#   DT.table.jaccard(genes.heart.plum1[c(11,4:6,3)])
#   
#  }

Hippocampus

Green

genes.hippocampus.green <- genes.jaccard.pathways(Matched, "Hippocampus_green")

Pathway Table

if(is.null(genes.hippocampus.green)) {
    print("No significant pathways")
  } else {genes.hippocampus.green <- genes.hippocampus.green$result
  DT.table.jaccard(genes.hippocampus.green[c(11,4:6,3)])
  
 }

Coral1

genes.hippocampus.coral1 <- genes.jaccard.pathways(Matched, "Hippocampus_coral1")

Pathway Table

if(is.null(genes.hippocampus.coral1)) {
    print("No significant pathways")
  } else {genes.hippocampus.coral1 <- genes.hippocampus.coral1$result
  DT.table.jaccard(genes.hippocampus.coral1[c(11,4:6,3)])
  
 }

Darkslateblue

genes.hippocampus.darkslateblue <- genes.jaccard.pathways(Matched, "Hippocampus_darkslateblue")

Pathway Table

if(is.null(genes.hippocampus.darkslateblue)) {
    print("No significant pathways")
  } else {genes.hippocampus.darkslateblue <- genes.hippocampus.darkslateblue$result
  DT.table.jaccard(genes.hippocampus.darkslateblue[c(11,4:6,3)])
  
 }

Darkolivegreen

genes.hippocampus.darkolivegreen <- genes.jaccard.pathways(Matched, "Hippocampus_darkolivegreen")

Pathway Table

if(is.null(genes.hippocampus.darkolivegreen)) {
    print("No significant pathways")
  } else {genes.hippocampus.darkolivegreen <- genes.hippocampus.darkolivegreen$result
  DT.table.jaccard(genes.hippocampus.darkolivegreen[c(11,4:6,3)])
  
 }
## [1] "No significant pathways"

Khaki3

genes.hippocampus.khaki3 <- genes.jaccard.pathways(Matched, "Hippocampus_khaki3")

Pathway Table

if(is.null(genes.hippocampus.khaki3)) {
    print("No significant pathways")
  } else {genes.hippocampus.khaki3 <- genes.hippocampus.khaki3$result
  DT.table.jaccard(genes.hippocampus.khaki3[c(11,4:6,3)])
  
 }
## [1] "No significant pathways"

Hypothalamus

midnightblue

genes.hypothalamus.midnightblue <- genes.jaccard.pathways(Matched, "Hypothalamus_midnightblue")

Pathway Table

if(is.null(genes.hypothalamus.midnightblue)) {
    print("No significant pathways")
  } else {genes.hypothalamus.midnightblue <- genes.hypothalamus.midnightblue$result
  DT.table.jaccard(genes.hypothalamus.midnightblue[c(11,4:6,3)])
  
 }

Bisque4

genes.hypothalamus.bisque4 <- genes.jaccard.pathways(Matched, "Hypothalamus_bisque4")

Pathway Table

if(is.null(genes.hypothalamus.bisque4)) {
    print("No significant pathways")
  } else {genes.hypothalamus.bisque4 <- genes.hypothalamus.bisque4$result
  DT.table.jaccard(genes.hypothalamus.bisque4[c(11,4:6,3)])
  
 }

Kidney

Lightyellow

genes.kidney.lightyellow <- genes.jaccard.pathways(Matched, "Kidney_lightyellow")

Pathway Table

if(is.null(genes.kidney.lightyellow)) {
    print("No significant pathways")
  } else {genes.kidney.lightyellow <- genes.kidney.lightyellow$result
  DT.table.jaccard(genes.kidney.lightyellow[c(11,4:6,3)])
  
 }

Purple

genes.kidney.purple <- genes.jaccard.pathways(Matched, "Kidney_purple")

Pathway Table

if(is.null(genes.kidney.purple)) {
    print("No significant pathways")
  } else {genes.kidney.purple <- genes.kidney.purple$result
  DT.table.jaccard(genes.kidney.purple[c(11,4:6,3)])
  
 }
## [1] "No significant pathways"

Lightcyan

genes.kidney.lightcyan <- genes.jaccard.pathways(Matched, "Kidney_lightcyan")

Pathway Table

if(is.null(genes.kidney.lightcyan)) {
    print("No significant pathways")
  } else {genes.kidney.lightcyan <- genes.kidney.lightcyan$result
  DT.table.jaccard(genes.kidney.lightcyan[c(11,4:6,3)])
  
 }
## [1] "No significant pathways"

Blue

Server won’t run this module currently

#genes.kidney.blue <- genes.jaccard.pathways(Matched, "Kidney_blue")

Pathway Table

# if(is.null(genes.kidney.blue)) {
#     print("No significant pathways")
#   } else {genes.kidney.blue <- genes.kidney.blue$result
#   DT.table.jaccard(genes.kidney.blue[c(11,4:6,3)])
#   
#  }

Pink

genes.kidney.pink <- genes.jaccard.pathways(Matched, "Kidney_pink")

Pathway Table

if(is.null(genes.kidney.pink)) {
    print("No significant pathways")
  } else {genes.kidney.pink <- genes.kidney.pink$result
  DT.table.jaccard(genes.kidney.pink[c(11,4:6,3)])
  
 }

Liver

Darkturquoise

genes.liver.darkturquoise <- genes.jaccard.pathways(Matched, "Liver_darkturquoise")

Pathway Table

if(is.null(genes.liver.darkturquoise)) {
    print("No significant pathways")
  } else {genes.liver.darkturquoise <- genes.liver.darkturquoise$result
  DT.table.jaccard(genes.liver.darkturquoise[c(11,4:6,3)])
  
 }

Darkolivegreen

genes.liver.darkolivegreen <- genes.jaccard.pathways(Matched, "Liver_darkolivegreen")

Pathway Table

if(is.null(genes.liver.darkolivegreen)) {
    print("No significant pathways")
  } else {genes.liver.darkolivegreen <- genes.liver.darkolivegreen$result
  DT.table.jaccard(genes.liver.darkolivegreen[c(11,4:6,3)])
  
 }

Skyblue3

genes.liver.skyblue3 <- genes.jaccard.pathways(Matched, "Liver_skyblue3")

Pathway Table

if(is.null(genes.liver.skyblue3)) {
    print("No significant pathways")
  } else {genes.liver.skyblue3 <- genes.liver.skyblue3$result
  DT.table.jaccard(genes.liver.skyblue3[c(11,4:6,3)])
  
 }

Prefrontal Cortex

Limegreen

genes.prefrontal.limegreen <- genes.jaccard.pathways(Matched, "Prefrontal Cortex_limegreen")

Pathway Table

if(is.null(genes.prefrontal.limegreen)) {
    print("No significant pathways")
  } else {genes.prefrontal.limegreen <- genes.prefrontal.limegreen$result
  DT.table.jaccard(genes.prefrontal.limegreen[c(11,4:6,3)])
  
 }
## [1] "No significant pathways"

Rosybrown2

genes.prefrontal.rosybrown2 <- genes.jaccard.pathways(Matched, "Prefrontal Cortex_rosybrown2")

Pathway Table

if(is.null(genes.prefrontal.rosybrown2)) {
    print("No significant pathways")
  } else {genes.prefrontal.rosybrown2 <- genes.prefrontal.rosybrown2$result
  DT.table.jaccard(genes.prefrontal.rosybrown2[c(11,4:6,3)])
  
 }

Lavenderblush2

genes.prefrontal.lavenderblush2 <- genes.jaccard.pathways(Matched, "Prefrontal Cortex_lavenderblush2")

Pathway Table

if(is.null(genes.prefrontal.lavenderblush2)) {
    print("No significant pathways")
  } else {genes.prefrontal.lavenderblush2 <- genes.prefrontal.lavenderblush2$result
  DT.table.jaccard(genes.prefrontal.lavenderblush2[c(11,4:6,3)])
  
 }

Antiquewhite

genes.prefrontal.antiquewhite <- genes.jaccard.pathways(Matched, "Prefrontal Cortex_antiquewhite")

Pathway Table

if(is.null(genes.prefrontal.antiquewhite)) {
    print("No significant pathways")
  } else {genes.prefrontal.antiquewhite <- genes.prefrontal.antiquewhite$result
  DT.table.jaccard(genes.prefrontal.antiquewhite[c(11,4:6,3)])
  
 }
## [1] "No significant pathways"

Pink

genes.prefrontal.pink <- genes.jaccard.pathways(Matched, "Prefrontal Cortex_pink")

Pathway Table

if(is.null(genes.prefrontal.pink)) {
    print("No significant pathways")
  } else {genes.prefrontal.pink <- genes.prefrontal.pink$result
  DT.table.jaccard(genes.prefrontal.pink[c(11,4:6,3)])
  
 }

Goldenrod3

genes.prefrontal.goldenrod3 <- genes.jaccard.pathways(Matched, "Prefrontal Cortex_goldenrod3")

Pathway Table

if(is.null(genes.prefrontal.goldenrod3)) {
    print("No significant pathways")
  } else {genes.prefrontal.goldenrod3 <- genes.prefrontal.goldenrod3$result
  DT.table.jaccard(genes.prefrontal.goldenrod3[c(11,4:6,3)])
  
 }
## [1] "No significant pathways"

Aquamarine

genes.prefrontal.aquamarine <- genes.jaccard.pathways(Matched, "Prefrontal Cortex_aquamarine")

Pathway Table

if(is.null(genes.prefrontal.aquamarine)) {
    print("No significant pathways")
  } else {genes.prefrontal.aquamarine <- genes.prefrontal.aquamarine$result
  DT.table.jaccard(genes.prefrontal.aquamarine[c(11,4:6,3)])
  
 }

Skeletal Muscle

Grey

genes.skeletal.grey <- genes.jaccard.pathways(Matched, "Skeletal Muscle_grey")

Pathway Table

if(is.null(genes.skeletal.grey)) {
    print("No significant pathways")
  } else {genes.skeletal.grey <- genes.skeletal.grey$result
  DT.table.jaccard(genes.skeletal.grey[c(11,4:6,3)])
  
 }

Small Intestine

Green4

genes.intestine.green4 <- genes.jaccard.pathways(Matched, "Small Intestine_green4")

Pathway Table

if(is.null(genes.intestine.green4)) {
    print("No significant pathways")
  } else {genes.intestine.green4 <- genes.intestine.green4$result
  DT.table.jaccard(genes.intestine.green4[c(11,4:6,3)])
  
 }

Blue2

genes.intestine.blue2 <- genes.jaccard.pathways(Matched, "Small Intestine_blue2")

Pathway Table

if(is.null(genes.intestine.blue2)) {
    print("No significant pathways")
  } else {genes.intestine.blue2 <- genes.intestine.blue2$result
  DT.table.jaccard(genes.intestine.blue2[c(11,4:6,3)])
  
 }

Cornsilk

genes.intestine.cornsilk <- genes.jaccard.pathways(Matched, "Small Intestine_cornsilk")

Pathway Table

if(is.null(genes.intestine.cornsilk)) {
    print("No significant pathways")
  } else {genes.intestine.cornsilk <- genes.intestine.cornsilk$result
  DT.table.jaccard(genes.intestine.cornsilk[c(11,4:6,3)])
  
 }

Magenta2

genes.intestine.magenta2 <- genes.jaccard.pathways(Matched, "Small Intestine_magenta2")

Pathway Table

if(is.null(genes.intestine.magenta2)) {
    print("No significant pathways")
  } else {genes.intestine.magenta2 <- genes.intestine.magenta2$result
  DT.table.jaccard(genes.intestine.magenta2[c(11,4:6,3)])
  
 }
## [1] "No significant pathways"

Darkgoldenrod4

genes.intestine.darkgoldenrod4 <- genes.jaccard.pathways(Matched, "Small Intestine_darkgoldenrod4")

Pathway Table

if(is.null(genes.intestine.darkgoldenrod4)) {
    print("No significant pathways")
  } else {genes.intestine.darkgoldenrod4 <- genes.intestine.darkgoldenrod4$result
  DT.table.jaccard(genes.intestine.darkgoldenrod4[c(11,4:6,3)])
  
 }
## [1] "No significant pathways"

Spleen

Tan4

genes.spleen.tan4 <- genes.jaccard.pathways(Matched, "Spleen_tan4")

Pathway Table

if(is.null(genes.spleen.tan4)) {
    print("No significant pathways")
  } else {genes.spleen.tan4 <- genes.spleen.tan4$result
  DT.table.jaccard(genes.spleen.tan4[c(11,4:6,3)])
  
 }

Mediumpurple1

genes.spleen.mediumpurple1 <- genes.jaccard.pathways(Matched, "Spleen_mediumpurple1")

Pathway Table

if(is.null(genes.spleen.mediumpurple1)) {
    print("No significant pathways")
  } else {genes.spleen.mediumpurple1 <- genes.spleen.mediumpurple1$result
  DT.table.jaccard(genes.spleen.mediumpurple1[c(11,4:6,3)])
  
 }

Palevioletred3

genes.spleen.palevioletred3 <- genes.jaccard.pathways(Matched, "Spleen_palevioletred3")

Pathway Table

if(is.null(genes.spleen.palevioletred3)) {
    print("No significant pathways")
  } else {genes.spleen.palevioletred3 <- genes.spleen.palevioletred3$result
  DT.table.jaccard(genes.spleen.palevioletred3[c(11,4:6,3)])
  
 }

Analysis performed by Ann Wells

The Carter Lab The Jackson Laboratory 2023

ann.wells@jax.org