10. Biomarkers Tab

The Biomarkers tab has a similar workflow with the biomarker information in the body of the tab and a biomarker snapshot and navigation section on the right sidebar. As the user scrolls down the body of this tab, the sections become more specialized as the sections cover first the gene level and then the biomarker level, and finally incorporate any clinical evidence. The top of the sidebar shows small cards for the biomarkers in this project (taken from the Biomarkers and Genes with Significant Wild-Types section of the Mutation Profile tab). As mentioned previously, we have 3 biomarkers in this project, and the first is the BRAF V600E Small Variant.

biomarkers summary example 2

Figure 10-1: The AMP Guidelines Biomarkers tab Summary section for Example 2.

The BRAF Gene Summary section is where we collect data about the BRAF gene, especially using the different catalog tools on the right. These descriptions and interpretations can be expanded and then copied using the plus signs at the end of each entry and pasted into the Interpretation on the left. Note that generally this is not a tumor type specific interpretation and will be re-used for all biomarkers in this gene.

biomarkers gene summary example 2

Figure 10-2: The AMP Guidelines Biomarkers tab Gene Summary section for Example 2.

The next section is BRAF Alteration Frequency and Outcomes and goal of this section is to analyze the gene in terms of the related tissue and tumor types and describe the frequency of mutation and prognostic outcomes related to biomarkers in this gene.

Also note that the interpretation information is specific to tumor type and will only show up with new samples with the same tumor type. The drop-down menu on the top of the section allows users to switch to a more broad tumor type if the selected one is too specific for the interpretation being written. Once changes are made to any of these interpretation sections, it is important to select the Review & Save Now… button to compare and save any changes.

biomarkers altertion frequency and outcomes

Figure 10-3: The AMP Guidelines Biomarkers tab Alteration Frequency and Outcomes section for Example 2.

The next section as we scroll down now moves from the broader gene level impact to the more specific biomarker level in *BRAF* V600E Biomarker Summary.

It is important to note that the biomarker interpretation is still specific to a tumor type as well as a biomarker scope. The scope should be changed at this point if the following clinical interpretation is not specific to the exact variant but more of a class of variants in a region or for the entire gene. For example, a loss-of-function variant in a tumor supressor gene should be interpreted at the broadest scope of “Gene LoF” so future variants in this gene that are loss-of-function share the same interpretation. In this case, BRAF V600E has specific clinical evidence and we will keep the scope at the level of this codon change.

The tabs on the Variant Classification and Details card present various sources of information about the current biomarker to assist in writting a high level summary of the biomarker (save clinical evidence for the remaining type-specific sections). If there are entries for this variant or other related variants in CancerKB or your own interpretation catalog, the will show up in the Related Interpretations and Related Interpretations in Other Tumor Type cards.

biomarkers biomarker summary example 2

Figure 10-4: The AMP Guidelines Biomarkers tab Biomarker Summary section for Example 2.

The final section in the biomarker page gets to the Clinical Evidence. This includes information covering Drug Sensitivity, Drug Resistance, Prognostic data, and Diagnostic data. These tables can also be sorted by drug name, tissue type, and type of evidence.

biomarkers clinical evidence example 2

Figure 10-5: The AMP Guidelines Biomarkers tab Clinical Evidence section for Example 2.

This information is used to start filling in the interpretation for the final report, including important drugs, and specifying the clinical evidence tier value. In this example, there are multiple FDA approved drug therapies for BRAF V600E, so this definitely shows a Tier I biomarker entry. The table contains an integration of relevant clinical sources, specifically DrugBank, PMKB and CIViC and are sorted by the strength of their clinical assertions. The details of each assertion is on the right when selecting each row, and often includes citations.

Next, we will look at the next biomarker by selecting the second card at the top of the right sidebar.