1. Initial plot options
Haplotype reference panel – Select a reference panel (e.g. 1000G)
Haplotype population set – Select the reference population to allow for data filtering and plotting based on linkage disequilibrium or minor allele frequencies. All populations and super populations from the 1000G reference set are available.
Imputation info threshold (inclusive) – Filter out variants with imputation info lower than this value. Range from 0 (plot all variants) to 1.
Minor allele frequency threshold (inclusive) – Filter out variants with MAF lower than this value in the selected population. Range from 0 (plot all variants) to 1.
Select View results.
2. Additional Manhattan plot viewing options
Once the required options have been configured and studies selected, they are rendered in the plotting area.
Further customise the plots with ‘Focal variant’ and ‘More plot options’ – located in the top bar, above the gene browser and plot viewing area (see figure 1).
Figure 1: Signal Explorer plot view, highlighting the Focal variant and More plot options features.
Focal variant – This defines the chromosome number, position of the variant, reference nucleotide base, and the alternative base (CPRA) used for linkage disequilibrium (LD) comparisons when colouring points by LD. If the CPRA falls within the defined region, it will be coloured cyan. If an LD-based ‘colour points by’ (see below) option is selected (including r, r2, D’), other variants are coloured based on the chosen LD metric, in respect of the focal CPRA. If no focal CPRA is specified, or the specified variant is not found in the LD reference panel, all points will instead be coloured grey.
To populate this field with the highest associated variant on the first plot, click the XXX button.
More plot options –
- Colour by – Choose from the following options:
- LD metrics r, r2, or D’ – values are shown in relation to the focal CPRA.
- MAF colours variants by minor allele frequency. LD and MAF options are dependent on the specified Haplotype Population Set.
- Info – colours each variant by the imputation info score. This value is based on Genomics imputation of summary-statistic imputation - not the info score reported by the original study. Variants imputed prior to acquisition by Genomics are reported as having an infoscore of 1.
- Y-axis maximum (optional): If set, the Y axis maximum of each plot will be set to this value. Points with a -log10(p) value greater than this will not be displayed.
- Variant effect highlighting: Coding variants can be highlighted, in green, depending on their VEP impact rating. HIGH/MODERATE/LOW or MODIFIER. This will override other colourings.
Plots are displayed in the order listed under ‘Selected datasets’ on the left. To reorder the plots, click and drag the listed datasets.
3. View the Manhattan plots
The plot area is composed of the Gene Browser panel and the Local Manhattan plot(s) (shown in figure 2).
Figure 2: Signal Explorer plot view, highlighting the Gene Browser panel and Manhattan plot areas.
Gene Browser panel – Indicates all the genes within the selected region, aligned with the plots beneath them. Protein-coding genes are represented by black bars while non-coding genes have grey bars.
Local Manhattan plot – Each variant is plotted according to its genomic position on the x-axis and -log10(p) of the association with the trait of interest on the y-axis. Points are coloured by the specified ‘colour by’ value (e.g. r2).
Key variant colouring and shape information is also displayed. The horizontal line drawn below -log10(p) = 10 represents the conventional genome wide significance threshold (-log10(p) = 7.3). Variants are plotted as triangles if they were imputed by Genomics at the summary statistic level, and circles otherwise. Variants highlighted in bright green are annotated as MEDIUM/HIGH impact missense variants in the Ensembl VEP database.
To identify a variant in the plot area, hover the cursor over a variant and click. An arrow will appear showing the CPRA ID. To copy the ID, hover over it and click.
To save the plot, click ‘Star view’, located xxx (see figure 3). Edit the name and description, as required, and click the save button.
Figure 3: Location of the save/star button in Signal Explorer.
To share the analysis, select the Share view button.
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