Sensitivity & Specificity
in Genomic Search
Thursday, August 27, 2020
Learn from the architects of Mastermind!
The Mastermind Genomic Search Engine was created to make it easy to find relevant genomic insight from the medical evidence. In the tug-of-war between Sensitivity and Specificity, Genomenon’s approach has been to first maximize sensitivity, and then optimize specificity within the scope of maximal sensitivity for the most efficient workflows and the best results.
Genomenon co-founders Dr. Mark Kiel and Steve Schwartz discuss how Mastermind optimizes specificity and then sensitivity when searching for insight into patient variants and resolving VUSs for optimal diagnostic yield. This approach provides insight for users to quickly validate (or invalidate) the search results.
- Best practices for genomic search to resolve Variants of Uncertain Significance (VUS) following AGMG guidelines
- Best practices when searching Mastermind to first maximize sensitivity, then strategically dial in the specificity of the search results
- How Mastermind continues to improve specificity for variants with less discrete biological effects, such as non-coding variants
ABOUT THE SPEAKERS:
Dr. Mark Kiel, Chief Science Officer – Genomenon
Mark Kiel completed his MD Ph.D. and Molecular Genetic Pathology Fellowship at the University of Michigan, where his research focused on stem cell biology, genomic profiling of hematopoietic malignancies, and clinical bioinformatics. He is the founder and CSO of Genomenon, where he supervises the scientific direction of the Mastermind suite of software tools.
Steve Schwartz, Chief Technology Officer – Genomenon
Steve is the CTO of Genomenon and key developer of the Mastermind technology. Steve is an engineer, developer, and open source software enthusiast. He co-founded several successful web-based software start-ups and brings deep domain expertise and extensive experience to the team.
How does this specificity approach apply to non-intronic variants?
With respect to the specificity of searching for variants at the nucleotide level, the same features of highlighting and preferentially prioritizing references that match the same nucleotide that the user searched for apply. Additionally, all of the features showcased in the webinar including categorical key terms, disease, phenotypes, therapies and free text searching also apply equally well to non-coding variants.
What happens if I don’t find my variant?
If your search result in Mastermind returns no results, this is highly useful on three fronts.
The first is that it very strongly suggests that the variant has never been described in the literature before given Mastermind’s comprehensive search of the entirety of the medical literature.
Second, Mastermind allows you very quickly to search for related variants (namely, of the same type or at the same residue, for instance) and review the references that cite these variants and determine how this information influences your decisions about the originally searched for variant.
Third, Mastermind allows your to create an Alert for the searched for variant to be notified the week that that variant is newly published and indexed in Mastermind.;
If you experience any difficulties finding references that cite a variant, please don’t hesitate to contact us to troubleshoot your search.
What human genome build been incorporated into your database?
Mastermind normalizes output results to GRCh38, but is capable of handling search queries for GRCh37 and earlier builds.
How does your database compare with the way that other databases index and display results?
Mastermind is a decision support tool that indexes the entirety of the medical literature using a sophisticated algorithm known as Genomics Language Processing (GLP) to very sensitively capture and organize all genetic variants irrespective of how they are described by authors – protein, cDNA or rsID, HGVS or non-standard descriptions, any transcript as well as legacy nomenclatures are all capture faithfully by Mastermind’s core technology. We then display all of these results in our interactive search interface that allows users to immediately verify the usefulness of any of the returned references for their variant interpretation.Mastermind is by far the most comprehensive database for literature curation and variant interpretation.
How are you different from PubMed?
Searches in PubMed return results limited to exact variant matches in the title and abstract of the references. Mastermind is a superset of such searches in that we index the entirety of the medical literature at the full-text and supplemental data. Searching in PubMed at the title and abstract level only returns around 6% of variants in the literature with a bias toward very well characterized variants.
Does Mastermind return relevant sentences in the main text even if my institution doesn’t have access?
Mastermind displays the sentence fragments of all references to all users irrespective of their access through their institution to any particular reference. Mastermind does NOT provide access to full copyrighted PDFs that users do not have their own independent access to.