Variant Detail Page¶
Users can access more information about a particular variant using the Variant Detail page (see clip below). To access this page, click anywhere (except on a hyperlink) within that variant's row in the Omics Explorer table. This is available in the Omics Summary view or in the Omics Filtered view.
The details available will depend on the variant selected.
- Gene - Gene name
- NC Change
- Position - Refers to the numeric chromosome position
- Variant Class
- Gene ID
- Transcript ID
- Gene Class
- VCF Qual
- VCF Filter
- EXON Number
- COSMIC Nearby
Genes can have many different transcripts. While they are all the same gene, they have different splicing/different exons. If you click on the Transcripts tab, you will see an Alternate Transcripts table. Here we denote the canonical transcript with a blue "i" info icon beside the transcript id. All other transcripts are listed beneath it (see image below).
- Transcript ID – Most canonical transcripts have a blue info dot beside it. If there is no dot, it means there is no canonical transcript identified because the way it was annotated did not specify it was part of the same gene.
- NC Damage
- AA Change
- Variant Class
- EXON Number
The CKB tab is where you can view any drug matches that correlate with the tumor variants.
CKB/Drug Association Table Columns:
- CKB - In the Cancer Knowledge Base
- Gene – Gene name
- Feature - Mutation
- Source – Source external database (civic, cosmic_resistmut, docm, pmkb, cgi)
- Drug – Name of drug associated with it
- Response Type – Tells how responsive it is to the drug. (Resistant, Responsive, better outcome, poor outcome)
- Evidence Level – AB, A (clinical practice/standard of care), B (some sort of clinical trial/off-label use data), C (early clinical trials/one case showed benefit), D (preclinical/mouse studies)
- Source Evidence – 1, 2, 3, Clinical evidence, Preclinical evidence, Validated association, Case study, Early trials
- Disease – Disease information (location/type)
- Publication – Links out to pubmed article regarding any gene drug association
- Comment - Any additional information is noted here
The Gene tab gives more information about the gene. This information is brought in from an external source (referenced in the summary).
- Summary - Tells more information about the gene
Needle Plot Tab¶
The Needleplot is a visual representation of where that mutation occurs in the protein. Hovering the cursor over the needle will tell you which mutation is at the needlepoint.
Reference Tissue Expression Tab¶
For Expression variants only, you can click on this tab on the Variant Details page to see the Reference Tissue Expression in:
- TCGA Cancer Type Tumor Samples (as seen in image below)
- TCGA Normal Samples
- GTEx Normal Broad Tissues
- GTEx Normal Specific Tissues
- TreeHouse Tumor Samples (Pediatric)
In the example shown in the image above, the purple horizontal line is the Expression for this patient in this sequencing test. The plot allows you to see how this expression relates to other cancer types. In the center of the plot, the chartreuse bar is the sum of All Diseases/Tissues.
If the gene we were looking at is highly expressed such as KIT is in this example, we can return to the Filtering page, click on Outliers to filter the genes that are highly expressed – greater than 2 std. deviations above the mean for TCGA expression. To do this we:
- Scroll down the list of filters and click on Outliers
- Under Compare Against Source select "TCGA Tumor Samples", and select All Diseases/Tissues
- Set #of std deviations to "2", and select "Above the mean"
Click Add Filter
In the example below, we clicked on the Germline Variant tab, and clicked the checkbox for CKB. The MAPK1 gene came back as a Gene Match, but the Variant Detail page shows no info under Drug Association. This means this gene has a known gene drug association, but this particular variant in this patient sample didn’t have an exact match to a drug.
Standalone Blue Dots
Blue dots appearing alone in a field of the Omics Explorer table means the canonical transcript does not meet that column criteria, but it's alternative transcript does meet the criteria. It lets you know there is more information about this gene.
For instance, in the clip below, we filter for missense variants. The results in the Omics Explorer table shows a variant with a blue dot in a blank field under both AA Change and Variant Class. This is because the canonical transcript does not have a missense variant. However, if we hover over the blue dot, it shows the alternate transcript which does have a missense variant. This is why it came through as a result for that missense filter.
Affects Alternate Transcript Example
In the example below, we filtered for missense variants. The Omics Explorer table shows a variant with a blue dot beside "missense" under the Variant Class column and a blue dot beside the "A128V" under the AA Change column.
The canonical transcript is a "Missense", but if you hover over the blue dot beside the word "missense", the words “intron variant” appear, meaning there is another transcript that labels this mutation as an intron variant and not a missense. Likewise, hovering over the blue dot beside the "A128V" AA Change, we’ll see 2 different AA changes from the canonical AA change shown in the table, A65V and A85V.
If we click on the row to view the Variant Detail (see image below) we see 10 transcripts, there is a beside the canonical transcript and is the one displayed in the Omics Explorer table. There are eight total transcripts with a missense mutation. And there are two intron variant mutations (seen when we hovered over the blue dot beside "missense" in the Variant Class column) but since it’s an intron, there is no AA Change.