Author: Myles Lewis

# Zoom browser

#### Myles Lewis

Here we demonstrate how to use the zoom browser to interactively browse whole genome GWAS or eQTL data within an R session. Via a shiny/plotly interface, users can click on peaks in a whole genome manhattan plot to zoom in and out of regions and pan left or right using the interactive browser.

### Example GWAS data

Example whole genome summary statistics from an SLE GWAS study can be downloaded from EBI here and loaded as follows. The main locuszoomr vignette shows how this data is formatted.

    # FTP download full summary statistics (308 MB) from SLE GWAS from
    # https://www.ebi.ac.uk/gwas/studies/GCST003156
    library(data.table)
    SLE_gwas <- fread('../bentham_2015_26502338_sle_efo0002690_1_gwas.sumstats.tsv')

The zoom browser is started using `zoom()`. Like the `locus()` function, `zoom()` tries to autodetect the columns for SNP id, chromosome, position and p-value. If you have complex or ambiguous column names, then the arguments `chrom`, `pos`, `p` and `labs` can be used to specify the appropriate columns in your dataset.

An appropriate hg19 or hg38 (or other species) ensembl database of genome information must be specified. In the example below, the GWAS data is hg19.

    library(locuszoomr)
    library(EnsDb.Hsapiens.v75)

    zoom(SLE_gwas, ens_db = "EnsDb.Hsapiens.v75")

### Navigation

Click on points in the whole genome or individual chromosome manhattan plots to explore a particular locus. Alternatively, enter a gene name or SNP id or chromosome position and location into the input text box. The locus plot can be navigated by zooming in/out, or moving left/right using the navigation icons. Dragging the locus plot will move the locus window. Also, the plotly selection tool can be used to select a specific region.

The icon allows users to toggle options such as showing the recombination rate (only if recomb data has been provided via `recomb` argument), expanding the gene tracks to show all genes, or selecting individual genes in eQTL data (if the `eqtl_gene` argument has been set).

### Add recombination rate

Recombination rate can be shown on a secondary y axis. Whole recombination rate track data file (around 30 MB) should be downloaded from UCSC genome browser (documented here).

The download site can be accessed at https://hgdownload.soe.ucsc.edu/gbdb/hg38/recombRate/. For hg38, download `recomb1000GAvg.bw`.

For hg19, the link is https://hgdownload.soe.ucsc.edu/gbdb/hg19/decode/ and the default track we use is `hapMapRelease24CombinedRecombMap.bw`.

The .bw track file can then be loaded into R as a `GRanges` object using `import.bw()`, and then used directly by `zoom()`.

    library(rtracklayer)
    recomb.hg19 <- import.bw("/../hapMapRelease24CombinedRecombMap.bw")

    zoom(SLE_gwas, ens_db = "EnsDb.Hsapiens.v75", recomb = recomb.hg19)

### Add LD via LDlink

The LDlink API can be queried from within the zoom browser. This requires an LDlink API access token, which can be obtained from the LDlink website. The token is then supplied via the `ld_token` argument when calling `zoom()`.

    zoom(SLE_gwas, ens_db = "EnsDb.Hsapiens.v75", recomb = recomb.hg19, ld_token = "my_token")

This enables extra buttons for `Get LD` in the settings dropdown menu. LD API requests are cached and retained during an R session, so subsequent requests for the same SNP are much faster. At each locus, the SNP with the lowest p-value is presumed to be the index SNP for LD requests. But clicking on other points can re-base the LD to alternative SNPs.

### Citation

If you use this package please cite as:

Lewis MJ, Wang S. (2025) locuszoomr: an R package for visualising publication-ready regional gene locus plots. Bioinformatics Advances 2025; vbaf006, doi:10.1093/bioadv/vbaf006