News

Failed run when larger number of variants are passed via the free text box solved  (October 12th)

We have recently updated one of the variant mapping tools employed by the public MTBP system (the Ensembl Variant Effect Predictor). This new version raises a default error when a larger number of variants is inputted if they are not ordered by chromosome position. However, we did not have this in place for variants passed via the ‘free text’ box of the public MTBP interface, which therefore caused a run error. This issue has now been fixed.  

-- david.tamborero@scilifelab.se , October 12th 2020

New report to provide the public MTBP analyses results (September 29th, 2020)

The results of the functional and predictive variant analyses provided by the public MTBP portal are now both included in a single document (two different html reports for each were used before).

On the one hand, the evidence supporting a functional (or neutral) role of a given variant to (putatively) acquire tumor traits is shown in the ‘Functional relevance evidence’ column. Of note, the functional interpretation is variant/allele centric and thus no further considerations (e.g. the sample’s cancer type) are taken into account here (e.g. an allele loss-of-function is always classified as so regardless of the context in which it is observed). Biomarker information is also integrated for the functional relevance interpretation, under the premise that a specific variant acting as a cancer biomarker is a functionally relevant event by definition.

In addition, variant information that is not conclusive (or relevant) for the functional classification but has been curated by one the employed knowledgebases (such as in an inconclusive ClinVar assertion or reported with a low allele frequency in population genomics databases) is now also included in this column (previously, such information was only shown in the advanced gene-variant view).

On the other hand, information about the predictive relevance (cancer prognosis, diagnostic and/or drug response) of the variant is now included in a new column named ‘Reported biomarker(s)’. In the public version of the MTBP, this analysis is solely based on the biomarkers reported by several public knowledgebases (CIViC, OncoKB and CancerGenomeInterpreter), which are updated in the portal on a regular basis (but not accessed in real time). Please note that this information is automatically aggregated by the annotation pipeline, as opposed to the MTBP instances employed by clinical projects such as Cancer Core Europe, in which the main actionability flags are manually curated based on in-house criteria. The public MTBP report provides a summary of the available information and the access to the corresponding knowledgebase entry for each given assertion via interactive popups (see image below).  

Of note, the biomarker interpretation is a phenotype-centric analysis, and thus considerations such as the cancer match (i.e. whether the biomarker has been described for the sample’s cancer type or a subtype thereof) and the current clinical relevance of that biomarker (such as ‘reported by early clinical trials’) are taken into account here. In detail, the matched biomarkers are automatically tiered following a modified version of the ESMO-ESCAT scale of actionability.

-- david.tamborero@scilifelab.se , September 29th 2020