G3viz: an R package to interactively visualize genetic mutation data using a lollipop-diagram
Xin Guo <g3viz.group at gmail.com>
2019-04-06
1 Introduction
Intuitively and effectively visualizing genetic mutation data can help researchers to better understand genomic data and validate findings. G3viz is an R package which provides an easy-to-use lollipop-diagram tool. It enables users to interactively visualize detailed translational effect of genetic mutations in RStudio or a web browser, without having to know any HTML5/JavaScript technologies.
The features of g3viz include
- Interactive (zoom & pan, tooltip, brush selection tool, and interactive legend)
- Highlight and label positional mutations
- 8 ready-to-use chart themes
- Highly customizable with over 50 chart options and over 35 color schemes
- Save charts in PNG or high-quality SVG format
- Built-in function to retrieve protein domain information and resolve gene isoforms
- Built-in function to map genetic mutation type (a.k.a, variant classification) to mutation class
2 Install g3viz
Install from R repository
or install development version from github
3 Quick Start
3.1 Example 1: Visualize genetic mutation data from MAF file
Mutation Annotation Format (MAF) is a commonly-used tab-delimited text file for storing aggregated mutation information. It could be generated from VCF file using tools like vcf2maf. Translational effect of variant alleles in MAF files are usually in the column named Variant_Classification or Mutation_Type (i.e., Frame_Shift_Del, Split_Site). In this example, the somatic mutation data of the TCGA-BRCA study was originally downloaded from the GDC Data Portal.
# System file
maf.file <- system.file("extdata", "TCGA.BRCA.varscan.somatic.maf.gz", package = "g3viz")
# ============================================
# Read in MAF file
# In addition to read data in, g3viz::readMAF function does
# 1. parse "Mutation_Class" information from the "Variant_Classification"
# column (also named "Mutation_Type" in some files)
# 2. parse "AA_position" (amino-acid position) from the "HGVSp_Short" column
# (also named "amino_acid_change" in some files) (e.g., p.Q136P)
# ============================================
mutation.dat <- readMAF(maf.file)# ============================================
# Chart 1
# "default" chart theme
# ============================================
chart.options <- g3Lollipop.theme(theme.name = "default",
title.text = "PIK3CA gene (default theme)")
g3Lollipop(mutation.dat,
gene.symbol = "PIK3CA",
plot.options = chart.options,
output.filename = "default_theme")
#> Factor is set to Mutation_Class
#> legend title is set to Mutation_Class3.2 Example 2: visualize genetic mutation data from CSV or TSV file
In this example, we read genetic mutation data from CSV or TSV files, and visualize it using some customized chart options. Note this is equivalent to dark chart theme.
# load data
mutation.csv <- system.file("extdata", "ccle.csv", package = "g3viz")
# ============================================
# read in data
# "gene.symbol.col" : column of gene symbol
# "variant.class.col" : column of variant class
# "protein.change.col" : colum of protein change column
# ============================================
mutation.dat <- readMAF(mutation.csv,
gene.symbol.col = "Hugo_Symbol",
variant.class.col = "Variant_Classification",
protein.change.col = "amino_acid_change",
sep = ",") # column-separator of csv file
# set up chart options
plot.options <- g3Lollipop.options(
# Chart settings
chart.width = 600,
chart.type = "pie",
chart.margin = list(left = 30, right = 20, top = 20, bottom = 30),
chart.background = "#d3d3d3",
transition.time = 300,
# Lollipop track settings
lollipop.track.height = 200,
lollipop.track.background = "#d3d3d3",
lollipop.pop.min.size = 1,
lollipop.pop.max.size = 8,
lollipop.pop.info.limit = 5.5,
lollipop.pop.info.dy = "0.24em",
lollipop.pop.info.color = "white",
lollipop.line.color = "#a9A9A9",
lollipop.line.width = 3,
lollipop.circle.color = "#ffdead",
lollipop.circle.width = 0.4,
lollipop.label.ratio = 2,
lollipop.label.min.font.size = 12,
lollipop.color.scheme = "dark2",
highlight.text.angle = 60,
# Domain annotation track settings
anno.height = 16,
anno.margin = list(top = 0, bottom = 0),
anno.background = "#d3d3d3",
anno.bar.fill = "#a9a9a9",
anno.bar.margin = list(top = 4, bottom = 4),
domain.color.scheme = "pie5",
domain.margin = list(top = 2, bottom = 2),
domain.text.color = "white",
domain.text.font = "italic 8px Serif",
# Y-axis label
y.axis.label = "# of TP53 gene mutations",
axis.label.color = "#303030",
axis.label.alignment = "end",
axis.label.font = "italic 12px Serif",
axis.label.dy = "-1.5em",
y.axis.line.color = "#303030",
y.axis.line.width = 0.5,
y.axis.line.style = "line",
y.max.range.ratio = 1.1,
# Chart title settings
title.color = "#303030",
title.text = "TP53 gene (customized chart options)",
title.font = "bold 12px monospace",
title.alignment = "start",
# Chart legend settings
legend = TRUE,
legend.margin = list(left=20, right = 0, top = 10, bottom = 5),
legend.interactive = TRUE,
legend.title = "Variant classification",
# Brush selection tool
brush = TRUE,
brush.selection.background = "#F8F8FF",
brush.selection.opacity = 0.3,
brush.border.color = "#a9a9a9",
brush.border.width = 1,
brush.handler.color = "#303030",
# tooltip and zoom
tooltip = TRUE,
zoom = TRUE
)
g3Lollipop(mutation.dat,
gene.symbol = "TP53",
protein.change.col = "amino_acid_change",
btn.style = "blue", # blue-style chart download buttons
plot.options = plot.options,
output.filename = "customized_plot")
#> Factor is set to Mutation_Class3.3 Example 3: visualize genetic mutation data from cBioPortal
cBioPortal provides download for many cancer genomics data sets. g3viz has a convenient way to retrieve data directly from this portal.
In this example, we first retrieve genetic mutation data of TP53 gene for the msk_impact_2017 study, and then visualize the data using the built-in cbioportal theme, to miminc cBioPortal’s mutation_mapper.
# Retrieve mutation data of "msk_impact_2017" from cBioPortal
mutation.dat <- getMutationsFromCbioportal("msk_impact_2017", "TP53")
#> Found study msk_impact_2017
#> Found mutation data set msk_impact_2017_mutations
#> 10945 cases in this study
# "cbioportal" chart theme
plot.options <- g3Lollipop.theme(theme.name = "cbioportal",
title.text = "TP53 gene (cbioportal theme)",
y.axis.label = "# of TP53 Mutations")
g3Lollipop(mutation.dat,
gene.symbol = "TP53",
btn.style = "gray", # gray-style chart download buttons
plot.options = plot.options,
output.filename = "cbioportal_theme")
#> Factor is set to Mutation_Class
#> legend title is set to Mutation_Class3.3.0.1 Note:
- Internet access is required to download data from cBioPortal. This may take more than 10 seconds, or sometimes it may fail.
- To check what studies are available on cBioPortal
# Connect to CGDS (cancer Genomics Data Server)
cgds <- cgdsr::CGDS("http://www.cbioportal.org/")
# Test if connection is OK
cgdsr::test(cgds)
# To list all studies
all.studies <- cgdsr::getCancerStudies(cgds)
# Pick up a cancer study with mutation data
mutation.dat <- g3viz::getMutationsFromCbioportal("all_stjude_2016", "TP53")4 Usage
4.1 Read data
In g3viz, annotated mutation data can be loaded in three ways
from
CSVorTSVfiles, as in Example 2.from cBioPortal (internet access required), as in Example 3.
4.2 Map mutation type to mutation class
In addtion to reading mutation data, readMAF or getMutationFromCbioportal functions also map mutation type to mutation class and generate a Mutation_Class column by default. Mutation type is usually in the column of Variant_Classification or Mutation_Type. The default mapping table is,
| Mutation_Type | Mutation_Class | Short_Name |
|---|---|---|
| Inframe | ||
| In_Frame_Del | Inframe | IF del |
| In_Frame_Ins | Inframe | IF ins |
| Silent | Inframe | Silent |
| Targeted_Region | Inframe | IF |
| Missense | ||
| Missense_Mutation | Missense | Missense |
| Truncating | ||
| Frame_Shift | Truncating | FS |
| Frame_Shift_Del | Truncating | FS del |
| Frame_Shift_Ins | Truncating | FS ins |
| Nonsense_Mutation | Truncating | Nonsense |
| Nonstop_Mutation | Truncating | Nonstop |
| Splice_Region | Truncating | Splice |
| Splice_Site | Truncating | Splice |
| Other | ||
| 3’Flank | Other | 3’Flank |
| 3’UTR | Other | 3’UTR |
| 5’Flank | Other | 5’Flank |
| 5’UTR | Other | 5’UTR |
| De_novo_Start_InFrame | Other | de_novo_start_inframe |
| De_novo_Start_OutOfFrame | Other | de_novo_start_outofframe |
| Fusion | Other | Fusion |
| IGR | Other | IGR |
| Intron | Other | Intron |
| lincRNA | Other | lincRNA |
| RNA | Other | RNA |
| Start_Codon_Del | Other | Nonstart |
| Start_Codon_Ins | Other | start_codon_ins |
| Start_Codon_SNP | Other | Nonstart |
| Translation_Start_Site | Other | TSS |
| Unknown | Other | Unknown |
4.3 Retrieve Pfam domain inforamtion
Given a HUGO gene symbol, users can either use hgnc2pfam function to retrieve Pfam protein domain information first or use all-in-one g3Lollipop function to directly create lollipop-diagram. In case that the given gene has multiple isoforms, hgnc2pfam returns all UniProt entries, and users can specify one using the corresponding UniProt entry. If attribute guess is TRUE, the Pfam domain information of the longest UniProt entry is returned.
# Example 1: TP53 has single UniProt entry
hgnc2pfam("TP53", output.format = "list")
#> $symbol
#> [1] "TP53"
#>
#> $uniprot
#> [1] "P04637"
#>
#> $length
#> [1] 393
#>
#> $pfam
#> hmm.acc hmm.name start end type
#> 37815 PF08563 P53_TAD 5 29 Motif
#> 37816 PF00870 P53 95 289 Domain
#> 37817 PF07710 P53_tetramer 319 358 Motif
# Example 2: GNAS has multiple UniProt entries
# `guess = TRUE`: the Pfam domain information of the longest
# UniProt protein is returned
hgnc2pfam("GNAS", guess = TRUE)
#> GNAS maps to multiple UniProt entries:
#> symbol uniprot length
#> GNAS O95467 245
#> GNAS P63092 394
#> GNAS P84996 626
#> GNAS Q5JWF2 1037
#> Warning in hgnc2pfam("GNAS", guess = TRUE): Pick: Q5JWF2
#> {"symbol":"GNAS","uniprot":"Q5JWF2","length":1037,"pfam":[{"hmm.acc":"PF00503","hmm.name":"G-alpha","start":663,"end":1026,"type":"Domain"}]}4.4 Chart themes
The g3viz package contains 8 ready-to-use chart schemes: default, blue, simple, cbioportal, nature, nature2, ggplot2, and dark. Check this tutorial for examples and usage.
4.5 Color schemes
Figure 1 demonstrates all color schemes that g3viz supports for lollipop-pops and Pfam domains. More demos are available at demo 1, demo 2, and demo 3.
Figure 1. List of color schemes supported by g3viz
4.6 Chart options
Chart options can be specified using g3Lollipop.options() function (see example 2). Here is the full list of chart options,
| Option | Description |
|---|---|
| Chart settings | |
| chart.width |
chart width in px. Default 800.
|
| chart.type |
pop type, pie or circle. Default pie.
|
| chart.margin |
specify chart margin in list format. Default list(left = 40, right = 20, top = 15, bottom = 25).
|
| chart.background |
chart background. Default transparent.
|
| transition.time |
chart animation transition time in millisecond. Default 600.
|
| Lollipop track settings | |
| lollipop.track.height |
height of lollipop track. Default 420.
|
| lollipop.track.background |
background of lollipop track. Default rgb(244,244,244).
|
| lollipop.pop.min.size |
lollipop pop minimal size in px. Default 2.
|
| lollipop.pop.max.size |
lollipop pop maximal size in px. Default 12.
|
| lollipop.pop.info.limit |
threshold of lollipop pop size to show count information in middle of pop. Default 8.
|
| lollipop.pop.info.color |
lollipop pop information text color. Default #EEE.
|
| lollipop.pop.info.dy |
y-axis direction text adjustment of lollipop pop information. Default -0.35em.
|
| lollipop.line.color |
lollipop line color. Default rgb(42,42,42).
|
| lollipop.line.width |
lollipop line width. Default 0.5.
|
| lollipop.circle.color |
lollipop circle border color. Default wheat.
|
| lollipop.circle.width |
lollipop circle border width. Default 0.5.
|
| lollipop.label.ratio |
lollipop click-out label font size to circle size ratio. Default 1.4.
|
| lollipop.label.min.font.size |
lollipop click-out label minimal font size. Default 10.
|
| lollipop.color.scheme |
color scheme to fill lollipop pops. Default accent. Check color schemes for details.
|
| highlight.text.angle |
the rotation angle of on-click highlight text in degree. Default 90.
|
| Domain annotation track settings | |
| anno.height |
height of protein structure annotation track. Default 30.
|
| anno.margin |
margin of protein structure annotation track. Default list(top = 4, bottom = 0).
|
| anno.background |
background of protein structure annotation track. Default transparent.
|
| anno.bar.fill |
background of protein bar in protein structure annotation track. Default #E5E3E1.
|
| anno.bar.margin |
margin of protein bar in protein structure annotation track. Default list(top = 2, bottom = 2).
|
| domain.color.scheme |
color scheme of protein domains. Default category10. Check color schemes for details.
|
| domain.margin |
margin of protein domains. Default list(top = 0, bottom = 0).
|
| domain.text.font |
domain label text font in shorthand format. Default normal 11px Arial.
|
| domain.text.color |
domain label text color. Default #F2F2F2.
|
| Y-axis settings | |
| y.axis.label |
Y-axis label text. Default # of mutations.
|
| axis.label.font |
css font style shorthand (font-style font-variant font-weight font-size/line-height font-family). Default normal 12px Arial.
|
| axis.label.color |
axis label text color. Default #4f4f4f.
|
| axis.label.alignment |
axis label text alignment (start/end/middle). Default middle
|
| axis.label.dy |
text adjustment of axis label text. Default -2em.
|
| y.axis.line.color |
color of y-axis in-chart lines (ticks). Default #c4c8ca.
|
| y.axis.line.style |
style of y-axis in-chart lines (ticks), dash or line. Default dash.
|
| y.axis.line.width |
width of y-axis in-chart lines (ticks). Default 1.
|
| y.max.range.ratio |
ratio of y-axis range to data value range. Default 1.1.
|
| Chart title settings | |
| title.text | title of chart. Default "". |
| title.font |
font of chart title. Default normal 16px Arial.
|
| title.color |
color of chart title. Default #424242.
|
| title.alignment |
text alignment of chart title (start/middle/end). Default middle.
|
| title.dy |
text adjustment of chart title. Default 0.35em.
|
| Chart legend settings | |
| legend |
if show legend. Default TRUE.
|
| legend.margin |
legend margin in list format. Default list(left = 10, right = 0, top = 5, bottom = 5).
|
| legend.interactive |
legend interactive mode. Default TRUE.
|
| legend.title |
legend title. If NA, use factor name as factor.col. Default is NA.
|
| Brush selection tool settings | |
| brush |
if show brush. Default TRUE.
|
| brush.selection.background |
background color of selection brush. Default #666.
|
| brush.selection.opacity |
background opacity of selection brush. Default 0.2.
|
| brush.border.color |
border color of selection brush. Default #969696.
|
| brush.handler.color |
color of left and right handlers of selection brush. Default #333.
|
| brush.border.width |
border width of selection brush. Default 1.
|
| Tooltip and zoom tools | |
| tooltip |
if show tooltip. Default TRUE.
|
| zoom |
if enable zoom feature. Default TRUE.
|
4.7 Save chart as HTML
g3Lollipop also renders two buttons over the lollipop-diagram, allowing to save the resulting chart in PNG or vector-based SVG file. To save chart programmatically as HTML, you can use htmlwidgets::saveWidget function.
5 Session Info
sessionInfo()
#> R version 3.5.1 (2018-07-02)
#> Platform: x86_64-apple-darwin15.6.0 (64-bit)
#> Running under: macOS 10.14.4
#>
#> Matrix products: default
#> BLAS: /Library/Frameworks/R.framework/Versions/3.5/Resources/lib/libRblas.0.dylib
#> LAPACK: /Library/Frameworks/R.framework/Versions/3.5/Resources/lib/libRlapack.dylib
#>
#> locale:
#> [1] en_US.UTF-8/en_US.UTF-8/en_US.UTF-8/C/en_US.UTF-8/en_US.UTF-8
#>
#> attached base packages:
#> [1] stats graphics grDevices utils datasets methods base
#>
#> other attached packages:
#> [1] kableExtra_1.1.0 knitr_1.22 g3viz_1.1.0
#>
#> loaded via a namespace (and not attached):
#> [1] Rcpp_1.0.1 rstudioapi_0.10 xml2_1.2.0
#> [4] magrittr_1.5 hms_0.4.2 munsell_0.5.0
#> [7] rvest_0.3.2 viridisLite_0.3.0 colorspace_1.4-1
#> [10] R6_2.4.0 rlang_0.3.4 highr_0.8
#> [13] httr_1.4.0 stringr_1.4.0 tools_3.5.1
#> [16] webshot_0.5.1 xfun_0.6 R.oo_1.22.0
#> [19] htmltools_0.3.6 yaml_2.2.0 digest_0.6.18
#> [22] tibble_2.1.1 crayon_1.3.4 readr_1.3.1
#> [25] cgdsr_1.2.10 htmlwidgets_1.3 glue_1.3.1
#> [28] evaluate_0.13 rmarkdown_1.12 stringi_1.4.3
#> [31] pillar_1.3.1 compiler_3.5.1 scales_1.0.0
#> [34] R.methodsS3_1.7.1 jsonlite_1.6 pkgconfig_2.0.2