Analysis
Last updated: 2022-10-27
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Knit directory: cirrhosis-metabolism/
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Introduction
This script analyzes the expression of genes involved in the metabolism of xenobiotic substances in one of our previously published mouse model that develops chronic liver disease induced by administration of CCl4 for 2, 6 and 12 months (Holland et al. 2021).
The focus is on the following gene families:
- Phase I
- Cytochrome p450 dependent monooxygenase (CYP)
- Flavin dependent monooxygenases (FMO)
- Monoamine oxidase (MAO)
- Cyclooxgenase (COX)
- Dihydrodioldehydrogenase (Not yet implemented)
- DT-Diaphorase (NQOR)
- Alcohol- and Aldehyddehydrogenase (ADH/ALDH)
- Epoxidhydrolase (Not yet implemented)
- Phase II
- Glutathiontransferase (GST)
- UDP-glucuronosyltransferase (UGT)
- Sulfotransferase (SULT)
- Acetyltransferase (NAT)
- Methyltransferase (MT)
Libraries and sources
These libraries and sources are used for this analysis.
# data wrangling
library(tidyverse)
# statistics
library(fgsea)
# plotting
library(cowplot)
library(lemon)
library(tidytext)
library(UpSetR)
library(plotly)
library(scales)
# colors
library(AachenColorPalette)
library(RColorBrewer)
# display tables
library(DT)
library(knitr)
# development helpers
library(here)
library(devtools)
# other
library(htmltools)
base_url <- "https://raw.githubusercontent.com/saezlab/liver-disease-atlas"
source_url(file.path(base_url, "master", "code", "utils-plots.R"))
source_url(file.path(base_url, "master", "code", "utils-utils.R"))Definition of global variables that are used throughout this analysis.
Metabolic genes
Annotate metabolic genes
This table displays all genes that are considered in this analysis
# extract all possible genes
genes <- readRDS(here(data_path, "count_matrix.rds")) |>
rownames_to_column("gene") |>
as_tibble() |>
select(gene)
genes <- genes |>
mutate(family = case_when(
str_detect(gene, "^Cyp") ~ "CYP",
str_detect(gene, "^Ugt") ~ "UGT",
str_detect(gene, "^Fmo") ~ "FMO",
str_detect(gene, "^Mao") ~ "MAO",
str_detect(gene, "^Cox") ~ "COX",
str_detect(gene, "^Adh|Aldh") ~ "ADH/ALDH",
str_detect(gene, "^Sult") ~ "SULT",
str_detect(gene, "^Nat") ~ "NAT",
str_detect(gene, "^Mt") ~ "MT",
str_detect(gene, "^Nqor") ~ "NQOR",
str_detect(gene, "^Gst") ~ "GST",
# str_detect(gene, "^xxx") ~ "Epoxidhydrolasen",
# str_detect(gene, "^xxx") ~ "Dihydrodioldehydrogenase",
TRUE ~ NA_character_
)) |>
drop_na(family) |>
mutate(phase = case_when(
family %in% c("CYP", "FMO", "MAO", "COX", "NQOR", "ADH/ALDH") ~ "Phase I",
family %in% c("GST", "UGT", "SULT", "NAT", "MT") ~ "Phase II",
)) |>
mutate(
family = as_factor(family),
phase = as_factor(phase)
) |>
select(phase, family, gene)
saveRDS(genes, here(output_path, "metabolic_genes.rds"))
datatable(genes)Number of metabolic genes
Fraction of differentially expressed metabolic genes
| phase | family | size | n | fraction |
|---|---|---|---|---|
| Phase I | MAO | 2 | 1 | 0.5000000 |
| Phase I | FMO | 8 | 3 | 0.3750000 |
| Phase I | CYP | 126 | 46 | 0.3650794 |
| Phase II | UGT | 22 | 8 | 0.3636364 |
| Phase II | GST | 23 | 8 | 0.3478261 |
| Phase II | NAT | 18 | 6 | 0.3333333 |
| Phase II | SULT | 27 | 9 | 0.3333333 |
| Phase I | ADH/ALDH | 29 | 9 | 0.3103448 |
| Phase II | MT | 72 | 7 | 0.0972222 |
Differentially expressed metabolic families arcoss time points
Enrichment analysis
Trajectories of metabolic genes
Only metabolic genes that are differentially expressed in at least one timepoint are considered.
Metabolic genes with pericentral location
The list of pericentral genes is taken from one of our previous studies (Ghallab et al. 2019).
Overlap of metabolic and pericentral genes
Trajectories of metabolic genes with pericentral location
Only genes that are differentially expressed in at least one timepoint are considered.
References
R version 4.2.1 (2022-06-23)
Platform: x86_64-apple-darwin17.0 (64-bit)
Running under: macOS Big Sur ... 10.16
Matrix products: default
BLAS: /Library/Frameworks/R.framework/Versions/4.2/Resources/lib/libRblas.0.dylib
LAPACK: /Library/Frameworks/R.framework/Versions/4.2/Resources/lib/libRlapack.dylib
locale:
[1] de_DE.UTF-8/de_DE.UTF-8/de_DE.UTF-8/C/de_DE.UTF-8/de_DE.UTF-8
attached base packages:
[1] stats graphics grDevices datasets utils methods base
other attached packages:
[1] htmltools_0.5.3 devtools_2.4.5.9000 usethis_2.1.6
[4] here_1.0.1 knitr_1.40 DT_0.26
[7] RColorBrewer_1.1-3 AachenColorPalette_1.1.3 scales_1.2.1
[10] plotly_4.10.0 UpSetR_1.4.0 tidytext_0.3.4
[13] lemon_0.4.5 cowplot_1.1.1 fgsea_1.22.0
[16] forcats_0.5.2 stringr_1.4.1 dplyr_1.0.10
[19] purrr_0.3.5 readr_2.1.3 tidyr_1.2.1
[22] tibble_3.1.8 ggplot2_3.3.6 tidyverse_1.3.2
[25] workflowr_1.7.0
loaded via a namespace (and not attached):
[1] googledrive_2.0.0 colorspace_2.0-3 ellipsis_0.3.2
[4] rprojroot_2.0.3 fs_1.5.2 rstudioapi_0.14
[7] farver_2.1.1 remotes_2.4.2 SnowballC_0.7.0
[10] fansi_1.0.3 lubridate_1.8.0 xml2_1.3.3
[13] codetools_0.2-18 cachem_1.0.6 pkgload_1.3.0
[16] jsonlite_1.8.3 broom_1.0.1 dbplyr_2.2.1
[19] shiny_1.7.2 compiler_4.2.1 httr_1.4.4
[22] backports_1.4.1 assertthat_0.2.1 Matrix_1.4-1
[25] fastmap_1.1.0 lazyeval_0.2.2 gargle_1.2.1
[28] cli_3.4.1 later_1.3.0 prettyunits_1.1.1
[31] tools_4.2.1 gtable_0.3.1 glue_1.6.2
[34] fastmatch_1.1-3 Rcpp_1.0.9 cellranger_1.1.0
[37] jquerylib_0.1.4 vctrs_0.5.0 crosstalk_1.2.0
[40] xfun_0.34 ps_1.7.1 rvest_1.0.3
[43] mime_0.12 miniUI_0.1.1.1 lifecycle_1.0.3
[46] renv_0.16.0 googlesheets4_1.0.1 getPass_0.2-2
[49] hms_1.1.2 promises_1.2.0.1 parallel_4.2.1
[52] curl_4.3.3 yaml_2.3.6 memoise_2.0.1
[55] gridExtra_2.3 sass_0.4.2 stringi_1.7.8
[58] highr_0.9 tokenizers_0.2.3 pkgbuild_1.3.1
[61] BiocParallel_1.30.4 rlang_1.0.6 pkgconfig_2.0.3
[64] evaluate_0.17 lattice_0.20-45 labeling_0.4.2
[67] htmlwidgets_1.5.4 processx_3.7.0 tidyselect_1.2.0
[70] plyr_1.8.7 magrittr_2.0.3 R6_2.5.1
[73] profvis_0.3.7 generics_0.1.3 DBI_1.1.3
[76] pillar_1.8.1 haven_2.5.1 whisker_0.4
[79] withr_2.5.0 janeaustenr_1.0.0 modelr_0.1.9
[82] crayon_1.5.2 utf8_1.2.2 urlchecker_1.0.1
[85] tzdb_0.3.0 rmarkdown_2.17 grid_4.2.1
[88] readxl_1.4.1 data.table_1.14.4 callr_3.7.2
[91] git2r_0.30.1 reprex_2.0.2 digest_0.6.30
[94] xtable_1.8-4 httpuv_1.6.6 munsell_0.5.0
[97] viridisLite_0.4.1 bslib_0.4.0 sessioninfo_1.2.2