Analysis of metabolic genes
Last updated: 2022-12-20
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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 Metablism
- Cytochrome p450 dependent monooxygenase (CYP)
- Flavin dependent monooxygenases (FMO)
- Monoamine oxidase (MAO)
- Cyclooxgenase (COX)
- Dihydrodioldehydrogenase (DH)
- DT-Diaphorase (NQOR)
- Alcohol- and Aldehyddehydrogenase (ADH/ALDH)
- Epoxidhydrolase (EPH)
- Phase II Metabolism
- Glutathiontransferase (GST)
- UDP-glucuronosyltransferase (UGT)
- Sulfotransferase (SULT)
- Acetyltransferase (NAT)
- Methyltransferase (MT)
- Carrier
- Blood side
- Canalicular side
Libraries and sources
These libraries and sources are used for this analysis.
# data wrangling
library(tidyverse)
# statistics
library(fgsea)
library(msigdf)
library(survcomp)
# plotting
library(cowplot)
library(lemon)
library(tidytext)
library(UpSetR)
library(plotly)
library(scales)
library(patchwork)
library(gtools)
# colors
library(AachenColorPalette)
library(RColorBrewer)
# display tables
library(DT)
library(knitr)
# development helpers
library(here)
library(devtools)
# other
library(htmltools)
# source scripts
source(here("code/plots.R"))
# source scripts from external projects
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.
Descriptive data 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, "^Eph") ~ "EPH",
str_detect(gene, "^Dh") ~ "DH",
TRUE ~ NA_character_
)) |>
drop_na(family) |>
mutate(phase = case_when(
family %in% c(
"CYP", "FMO", "MAO", "COX", "NQOR", "ADH/ALDH", "EPH", "DH"
) ~ "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)
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 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 | CYP | 126 | 40 | 0.3174603 |
| Phase I | ADH/ALDH | 29 | 9 | 0.3103448 |
| Phase I | EPH | 18 | 4 | 0.2222222 |
| Phase II | MT | 72 | 7 | 0.0972222 |
| Phase I | DH | 35 | 1 | 0.0285714 |
Carrier genes
Annotate carrier genes
Fraction of differentially expressed carrier genes
| side | size | n | fraction |
|---|---|---|---|
| Blood | 8 | 5 | 0.625 |
| Canalicular | 10 | 4 | 0.400 |
Overlap of metabolic, carrier and pericentral genes
| Version | Author | Date |
|---|---|---|
| bacff3d | christianholland | 2022-11-29 |
Top differentially expressed metabolic and carrier genes
Tranlational analysis
Translation of human genes to mouse genes
Trajectories
Metabolic genes
Only metabolic genes that are differentially expressed in at least one timepoint are considered.
Carrier genes
Only genes that are differentially expressed in at least one timepoint are considered.
Publication figures
Figure 1
PCA
Enrichemnt
Top DEGs
Warning: Removed 1 rows containing missing values (geom_text).Warning: Removed 2 rows containing missing values (geom_text).Warning: Removed 1 rows containing missing values (geom_text).
Removed 1 rows containing missing values (geom_text).Warning: Removed 2 rows containing missing values (geom_text).Warning: Removed 3 rows containing missing values (geom_text).Warning: Removed 6 rows containing missing values (geom_text).Warning: Removed 1 rows containing missing values (geom_text).Warning: Removed 5 rows containing missing values (geom_text).Warning: Removed 6 rows containing missing values (geom_text).Warning: Removed 5 rows containing missing values (geom_text).Warning: Removed 2 rows containing missing values (geom_text).# A tibble: 13 × 7
geneset phase geneset_label n data p pp
<fct> <fct> <chr> <int> <list> <list> <list>
1 Blood <NA> Blood side carrier 3 <tibble> <patchwrk> <tibble>
2 Canalicular <NA> Canalicular side car… 3 <tibble> <patchwrk> <tibble>
3 ADH/ALDH Phase I Alcohol- and aldehyd… 5 <tibble> <patchwrk> <tibble>
4 CYP Phase I Cytochrome p450 depe… 10 <tibble> <patchwrk> <tibble>
5 DH Phase I Dihydrodioldehydroge… 1 <tibble> <patchwrk> <tibble>
6 EPH Phase I Epoxidhydrolases (EP… 3 <tibble> <patchwrk> <tibble>
7 FMO Phase I Flavin dependent mon… 3 <tibble> <patchwrk> <tibble>
8 GST Phase II Glutathiontransferas… 7 <tibble> <patchwrk> <tibble>
9 MAO Phase I Monoamine oxidases (… 1 <tibble> <patchwrk> <tibble>
10 MT Phase II Methyltransferases (… 6 <tibble> <patchwrk> <tibble>
11 NAT Phase II Acetyltransferases (… 6 <tibble> <patchwrk> <tibble>
12 SULT Phase II Sulfotransferases (S… 7 <tibble> <patchwrk> <tibble>
13 UGT Phase II UDP-glucuronosyltran… 5 <tibble> <patchwrk> <tibble>Figure 2
Single correlations
Correlation heatmap
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 gtools_3.9.4
[10] patchwork_1.1.2 scales_1.2.1 plotly_4.10.0
[13] UpSetR_1.4.0 tidytext_0.3.4 lemon_0.4.5
[16] cowplot_1.1.1 survcomp_1.46.0 prodlim_2019.11.13
[19] survival_3.3-1 msigdf_7.4 fgsea_1.22.0
[22] forcats_0.5.2 stringr_1.4.1 dplyr_1.0.10
[25] purrr_0.3.5 readr_2.1.3 tidyr_1.2.1
[28] tibble_3.1.8 ggplot2_3.3.6 tidyverse_1.3.2
[31] workflowr_1.7.0
loaded via a namespace (and not attached):
[1] readxl_1.4.1 backports_1.4.1 fastmatch_1.1-3
[4] systemfonts_1.0.4 plyr_1.8.7 lazyeval_0.2.2
[7] splines_4.2.1 crosstalk_1.2.0 BiocParallel_1.30.4
[10] listenv_0.8.0 SnowballC_0.7.0 digest_0.6.30
[13] SuppDists_1.1-9.7 fansi_1.0.3 magrittr_2.0.3
[16] memoise_2.0.1 googlesheets4_1.0.1 tzdb_0.3.0
[19] remotes_2.4.2 globals_0.16.2 modelr_0.1.9
[22] prettyunits_1.1.1 colorspace_2.0-3 rvest_1.0.3
[25] textshaping_0.3.6 haven_2.5.1 xfun_0.34
[28] callr_3.7.2 crayon_1.5.2 jsonlite_1.8.3
[31] glue_1.6.2 gtable_0.3.1 gargle_1.2.1
[34] pkgbuild_1.3.1 future.apply_1.10.0 DBI_1.1.3
[37] miniUI_0.1.1.1 Rcpp_1.0.9 viridisLite_0.4.1
[40] xtable_1.8-4 lava_1.7.0 profvis_0.3.7
[43] htmlwidgets_1.5.4 httr_1.4.4 ellipsis_0.3.2
[46] farver_2.1.1 urlchecker_1.0.1 pkgconfig_2.0.3
[49] sass_0.4.2 dbplyr_2.2.1 utf8_1.2.2
[52] labeling_0.4.2 tidyselect_1.2.0 rlang_1.0.6
[55] later_1.3.0 munsell_0.5.0 cellranger_1.1.0
[58] tools_4.2.1 cachem_1.0.6 cli_3.4.1
[61] generics_0.1.3 broom_1.0.1 evaluate_0.17
[64] fastmap_1.1.0 ragg_1.2.3 yaml_2.3.6
[67] bootstrap_2019.6 processx_3.7.0 fs_1.5.2
[70] nlme_3.1-157 future_1.29.0 whisker_0.4
[73] mime_0.12 xml2_1.3.3 tokenizers_0.2.3
[76] compiler_4.2.1 rstudioapi_0.14 curl_4.3.3
[79] reprex_2.0.2 bslib_0.4.0 stringi_1.7.8
[82] highr_0.9 ps_1.7.1 lattice_0.20-45
[85] Matrix_1.4-1 survivalROC_1.0.3.1 vctrs_0.5.0
[88] pillar_1.8.1 lifecycle_1.0.3 jquerylib_0.1.4
[91] data.table_1.14.4 httpuv_1.6.6 R6_2.5.1
[94] promises_1.2.0.1 renv_0.16.0 KernSmooth_2.23-20
[97] gridExtra_2.3 janeaustenr_1.0.0 parallelly_1.32.1
[100] sessioninfo_1.2.2 codetools_0.2-18 assertthat_0.2.1
[103] pkgload_1.3.0 rprojroot_2.0.3 withr_2.5.0
[106] mgcv_1.8-40 parallel_4.2.1 hms_1.1.2
[109] grid_4.2.1 rmarkdown_2.17 googledrive_2.0.0
[112] git2r_0.30.1 getPass_0.2-2 shiny_1.7.2
[115] lubridate_1.8.0 rmeta_3.0