ggkegg
29 October 2024
1 ggkegg
This package aims to import, parse, and analyze KEGG data such as KEGG PATHWAY and KEGG MODULE. The package supports visualizing KEGG information using ggplot2 and ggraph through using the grammar of graphics. The package enables the direct visualization of the results from various omics analysis packages and the connection to the other tidy manipulation packages. In this documentation, the basic usage of ggkegg is presented. Please refer to the documentation for the detailed usage.
1.1 Introduction
There are many great packages performing KEGG PATHWAY analysis in R. pathview fetches KEGG PATHWAY information, enabling the output of images reflecting various user-defined values on the map. KEGGlincs can overlay LINCS data to KEGG PATHWAY, and examine the map using Cytoscape. graphite acquires pathways including KEGG and Reactome, convert them into graphNEL format, and provides an interface for topological analysis. KEGGgraph also downloads KEGG PATHWAY information and converts it into a format analyzable in R. Extending to these packages, the purpose of developing this package, ggkegg, is to allow for tidy manipulation of KEGG information by the power of tidygraph, to plot the relevant information in flexible and customizable ways using grammar of graphics, to examine the global and overview maps consisting of compounds and reactions.
1.2 Pathway
The users can obtain a KEGG PATHWAY tbl_graph by pathway function. If you want to cache the file, please specify use_cache=TRUE, and if you already have the XML files of the pathway, please specify the directory of the file with directory argument. Here, we obtain Cell cycle pathway (hsa04110) using cache. pathway_id column is inserted to node and edge by default, which allows for the identification of the pathway ID in the other functions.
library(ggkegg)
library(tidygraph)
library(dplyr)
graph <- ggkegg::pathway("hsa04110", use_cache=TRUE)
graph## # A tbl_graph: 134 nodes and 157 edges
## #
## # A directed acyclic multigraph with 40 components
## #
## # Node Data: 134 × 18 (active)
## name type reaction graphics_name x y width height fgcolor bgcolor
## <chr> <chr> <chr> <chr> <dbl> <dbl> <dbl> <dbl> <chr> <chr>
## 1 hsa:10… gene <NA> CDKN2A, ARF,… 532 -218 46 17 #000000 #BFFFBF
## 2 hsa:51… gene <NA> FZR1, CDC20C… 981 -630 46 17 #000000 #BFFFBF
## 3 hsa:41… gene <NA> MCM2, BM28, … 553 -681 46 17 #000000 #BFFFBF
## 4 hsa:23… gene <NA> ORC6, ORC6L.… 494 -681 46 17 #000000 #BFFFBF
## 5 hsa:10… gene <NA> ANAPC10, APC… 981 -392 46 17 #000000 #BFFFBF
## 6 hsa:10… gene <NA> ANAPC10, APC… 981 -613 46 17 #000000 #BFFFBF
## 7 hsa:65… gene <NA> SKP1, EMC19,… 188 -613 46 17 #000000 #BFFFBF
## 8 hsa:65… gene <NA> SKP1, EMC19,… 432 -285 46 17 #000000 #BFFFBF
## 9 hsa:983 gene <NA> CDK1, CDC2, … 780 -562 46 17 #000000 #BFFFBF
## 10 hsa:701 gene <NA> BUB1B, BUB1b… 873 -392 46 17 #000000 #BFFFBF
## # ℹ 124 more rows
## # ℹ 8 more variables: graphics_type <chr>, coords <chr>, xmin <dbl>,
## # xmax <dbl>, ymin <dbl>, ymax <dbl>, orig.id <chr>, pathway_id <chr>
## #
## # Edge Data: 157 × 6
## from to type subtype_name subtype_value pathway_id
## <int> <int> <chr> <chr> <chr> <chr>
## 1 118 39 GErel expression --> hsa04110
## 2 50 61 PPrel inhibition --| hsa04110
## 3 50 61 PPrel phosphorylation +p hsa04110
## # ℹ 154 more rowsThe output can be analysed readily using tidygraph and dplyr verbs. For example, centrality calculations can be performed as follows.
graph |>
mutate(degree=centrality_degree(mode="all"),
betweenness=centrality_betweenness()) |>
activate(nodes) |>
filter(type=="gene") |>
arrange(desc(degree)) |>
as_tibble() |>
relocate(degree, betweenness)## # A tibble: 112 × 20
## degree betweenness name type reaction graphics_name x y width
## <dbl> <dbl> <chr> <chr> <chr> <chr> <dbl> <dbl> <dbl>
## 1 11 144 hsa:7157 gene <NA> TP53, BCC7, … 590 -337 46
## 2 10 8 hsa:993 gene <NA> CDC25A, CDC2… 614 -496 46
## 3 9 0 hsa:983 gene <NA> CDK1, CDC2, … 689 -562 46
## 4 9 78.7 hsa:5925 gene <NA> RB1, OSRC, P… 353 -630 46
## 5 8 15 hsa:5347 gene <NA> PLK1, PLK, S… 862 -562 46
## 6 8 7 hsa:1111 h… gene <NA> CHEK1, CHK1,… 696 -393 46
## 7 7 0 hsa:983 gene <NA> CDK1, CDC2, … 780 -562 46
## 8 7 161. hsa:1026 gene <NA> CDKN1A, CAP2… 459 -407 46
## 9 7 5 hsa:994 hs… gene <NA> CDC25B... 830 -496 46
## 10 6 7 hsa:9088 gene <NA> PKMYT1, MYT1… 763 -622 46
## # ℹ 102 more rows
## # ℹ 11 more variables: height <dbl>, fgcolor <chr>, bgcolor <chr>,
## # graphics_type <chr>, coords <chr>, xmin <dbl>, xmax <dbl>, ymin <dbl>,
## # ymax <dbl>, orig.id <chr>, pathway_id <chr>1.2.1 Plot the pathway using ggraph
The parsed tbl_graph can be used to plot the information by ggraph using the grammar of graphics. The components in the graph such as nodes, edges, and text can be plotted layer by layer.
graph <- graph |> mutate(showname=strsplit(graphics_name, ",") |>
vapply("[", 1, FUN.VALUE="a"))
ggraph(graph, layout="manual", x=x, y=y)+
geom_edge_parallel(aes(linetype=subtype_name),
arrow=arrow(length=unit(1,"mm"), type="closed"),
end_cap=circle(1,"cm"),
start_cap=circle(1,"cm"))+
geom_node_rect(aes(fill=I(bgcolor),
filter=type == "gene"),
color="black")+
geom_node_text(aes(label=showname,
filter=type == "gene"),
size=2)+
theme_void()
Besides the default ordering, various layout functions in igraph and ggraph can be used.
graph |> mutate(x=NULL, y=NULL) |>
ggraph(layout="nicely")+
geom_edge_parallel(aes(color=subtype_name),
arrow=arrow(length=unit(1,"mm"), type="closed"),
end_cap=circle(0.1,"cm"),
start_cap=circle(0.1,"cm"))+
geom_node_point(aes(filter=type == "gene"),
color="black")+
geom_node_point(aes(filter=type == "group"),
color="tomato")+
geom_node_text(aes(label=showname,
filter=type == "gene"),
size=3, repel=TRUE, bg.colour="white")+
scale_edge_color_viridis(discrete=TRUE)+
theme_void()
1.3 Converting identifiers
In the above example, graphics_name column in the node table were used, which are available in the default KGML file. Some of them are truncated, and the user can convert identifiers using convert_id function to be used in mutate. One can pipe the functions to convert name column consisting of hsa KEGG gene IDs in node table of tbl_graph.
graph |>
activate(nodes) |>
mutate(hsa=convert_id("hsa")) |>
filter(type == "gene") |>
as_tibble() |>
relocate(hsa)## # A tibble: 112 × 20
## hsa name type reaction graphics_name x y width height fgcolor
## <chr> <chr> <chr> <chr> <chr> <dbl> <dbl> <dbl> <dbl> <chr>
## 1 CDKN2A hsa:10… gene <NA> CDKN2A, ARF,… 532 -218 46 17 #000000
## 2 FZR1 hsa:51… gene <NA> FZR1, CDC20C… 981 -630 46 17 #000000
## 3 MCM2 hsa:41… gene <NA> MCM2, BM28, … 553 -681 46 17 #000000
## 4 ORC6 hsa:23… gene <NA> ORC6, ORC6L.… 494 -681 46 17 #000000
## 5 ANAPC10 hsa:10… gene <NA> ANAPC10, APC… 981 -392 46 17 #000000
## 6 ANAPC10 hsa:10… gene <NA> ANAPC10, APC… 981 -613 46 17 #000000
## 7 SKP1 hsa:65… gene <NA> SKP1, EMC19,… 188 -613 46 17 #000000
## 8 SKP1 hsa:65… gene <NA> SKP1, EMC19,… 432 -285 46 17 #000000
## 9 CDK1 hsa:983 gene <NA> CDK1, CDC2, … 780 -562 46 17 #000000
## 10 BUB1B hsa:701 gene <NA> BUB1B, BUB1b… 873 -392 46 17 #000000
## # ℹ 102 more rows
## # ℹ 10 more variables: bgcolor <chr>, graphics_type <chr>, coords <chr>,
## # xmin <dbl>, xmax <dbl>, ymin <dbl>, ymax <dbl>, orig.id <chr>,
## # pathway_id <chr>, showname <chr>1.3.1 Highlighting set of nodes and edges
highlight_set_nodes() and highlight_set_edges() can be used to identify nodes that satisfy query IDs. Nodes often have multiple IDs, and user can choose how="any" (if one of identifiers in the nodes matches the query) or how="all" (if all of the identifiers in the nodes match the query) to highlight.
graph |>
activate(nodes) |>
mutate(highlight=highlight_set_nodes("hsa:7157")) |>
ggraph(layout="manual", x=x, y=y)+
geom_node_rect(aes(fill=I(bgcolor),
filter=type == "gene"), color="black")+
geom_node_rect(aes(fill="tomato", filter=highlight), color="black")+
geom_node_text(aes(label=showname,
filter=type == "gene"), size=2)+
geom_edge_parallel(aes(linetype=subtype_name),
arrow=arrow(length=unit(1,"mm"),
type="closed"),
end_cap=circle(1,"cm"),
start_cap=circle(1,"cm"))+
theme_void()
1.3.2 Overlaying raw KEGG image
We can use overlay_raw_map to overlay the raw KEGG images on the created ggraph.
The node and text can be directly customized by using various geoms, effects such as ggfx, and scaling functions.
The code below creates nodes using default parsed background color and just overlay the image.
graph |>
mutate(degree=centrality_degree(mode="all")) |>
ggraph(graph, layout="manual", x=x, y=y)+
geom_node_rect(aes(fill=degree,
filter=type == "gene"))+
overlay_raw_map()+
scale_fill_viridis_c()+
theme_void()
1.4 Module and Network
1.4.1 Parsing module
KEGG MODULE can be parsed and used in the analysis. The formula to obtain module is the same as pathway. Here, we use test pathway which contains two KEGG ORTHOLOGY, two compounds and one reaction.
This will create kegg_module class object storing definition and reactions.
mod <- module("M00002", use_cache=TRUE)
mod## M00002
## Glycolysis, core module involving three-carbon compounds1.4.2 Visualizing module
The module can be visualized by text-based or network-based, depicting how the KOs interact each other.
For text based visualization like the one shown in the original KEGG website, module_text can be used.
## Text-based
mod |>
module_text() |> ## return data.frame
plot_module_text()
For network based visualization, obtain_sequential_module_definition can be used.
## Network-based
mod |>
obtain_sequential_module_definition() |> ## return tbl_graph
plot_module_blocks()
We can assess module completeness, as well as user-defined module abundances. Please refer to the module section of documentation. The network can be created by the same way, and create kegg_network class object storing information.
1.4.3 Use with the other omics packages
The package supports direct importing and visualization, and investigation of the results of the other packages such as enrichment analysis results from clusterProfiler and differential expression analysis results from DESeq2. Pplease refer to use cases in the documentation for more detailed use cases.
1.5 Wrapper function ggkegg
ggkegg function can be used with various input. For example, if the user provides pathway ID, the function automatically returns the ggraph with the original layout, which can be used directly for stacking geoms. The other supported IDs are module, network, and also the enrichResult object, and the other options such as converting IDs are available.
ggkegg("bpsp00270") |> class() ## Returns ggraph## [1] "ggraph" "gg" "ggplot"ggkegg("N00002") ## Returns the KEGG NETWORK plot
sessionInfo()## R version 4.4.1 (2024-06-14)
## Platform: x86_64-pc-linux-gnu
## Running under: Ubuntu 24.04.1 LTS
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## time zone: America/New_York
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##
## attached base packages:
## [1] stats graphics grDevices utils datasets methods base
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## other attached packages:
## [1] dplyr_1.1.4 ggkegg_1.4.0 tidygraph_1.3.1 igraph_2.1.1
## [5] XML_3.99-0.17 ggraph_2.2.1 ggplot2_3.5.1 BiocStyle_2.34.0
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