Mastermind Masterclass:
CNV Search

Thursday, October 15th, 2020

The October 2020 release of the Mastermind Genomic Search Engine supports a long-awaited function: CNV Search! Watch the recording to learn from the architects of Mastermind how searching by CNV will accelerate your clinical workflow!

Copy-number variations (CNVs) cause 5-30% of genetic diseases, making them a vital component to any clinical interpretation pipeline. CNVs are highly heterogeneous, and currently available databases are difficult to navigate and contain limited or outdated information. This makes interpretation of CNVs extremely challenging and time-consuming. In addition, evolving and inconsistent nomenclature for CNV reporting over time has created significant challenges in searching for evidence in the literature, which can result in missing information relevant to diagnosis and interpretation.

This new feature allows users to identify CNV citations from full-text articles no matter how authors have described them, and to discover how they are associated with clinical diseases and phenotypes.

In this webinar, we take a use-case approach to highlighting the new CNV capability and showcase the benefits that Mastermind can provide to cytogeneticists and variant scientists when searching for CNVs, large and small.


  • How to search the medical literature for CNVs by karyotype, cytoband, chromosomal range, and gene/exon deletion/amplification using Mastermind
  • How to comprehensively review prioritized references citing a searched-for CNV for clinical interpretation and reporting
  • How to rapidly identify driver genes within a patient’s CNV based on phenotypic presentation

CNV search is available in Mastermind Professional Edition.

Questions & Answers About CNV Search

Q: How did you solve the problem which is caused by changed ref genome (different genome coordinates)?

A: We use GRCh38 by default for normalizing CNV references across different nomenclatures, but lift over coordinates from GRCH37 (hg19) when specified by either an author or user within their nomenclature.

Q: When you search CNVs in literature, do you perform reciprocal overlap or one way overlap? What is the overlap percent cutoff you use?

A: We do calculate reciprocal overlap and show both the percent reciprocal overlap and number of overlapping base-pairs when you hover over the overlap-type in the “Overlap” column.
The cutoff is 0% overlap; even a single-nucleotide overlapping CNV will be included in the results by default, but can easily be sorted to the bottom by sorting the CNV list on the “Overlap” column.

Q: Do you index articles based on legacy exon numbering, as well as systematic versus custom exon numbering? This is an issue I have struggled with quite a bit in performing literature searches for CNVs.

A: Right now, we are aware of issues with legacy exon numbering, as we have handled similar issues with variants for example using IVS nomenclature with legacy intron numbering. For now, CNVs are normalized by matching the exon numbers to the longest transcript and mapping that to the GRCh38 reference build.
You can easily see legacy citations using different exon numbers by searching for deletions or amplifications of the entire gene, then sorting the CNV list based on start position to see references using alternate exon numbers. You could then click the legacy exon numbers and sort the article list by publication date to focus on older articles more likely using legacy numbering.
If you are aware of specific genes and examples of this issue, please reach out to and let us know so that we can consider incorporating corrections for the genes into our Genomic Language Processing pipeline.

Q: If I search for a deletion in a certain region, would it also show any duplication associated with that region?

A: Currently, the default search functionality shows overlapping CNVs with the same effect (either deletion or duplication/amplification). If you want to see either/or, you can do an Advanced (Boolean) search for both the deletion and amplification and change the comparison operator between the two to “or”, which will show results citing either one or the other. The CNV list will also then show all overlapping CNVs of either deletion or amplification types.

Q: Is there a way to filter literature results by somatic vs germline?

A: Mastermind has keywords for “somatic” and “germline” that help filter less relevant content and prioritize more relevant content. Additionally, if there is a specific disease of interest, any specific disease or phenotype can be used as a filter as well.

Q: Is it possible to perform a batch query for a list of CNVs?

A: This will be possible with the API, coming soon

Q: Additional to the CNV feature I wonder if it is possible to search according to the Tier classification for somatic variants?

A: While Mastermind Genomic Search Engine does not itself have pre-categorized Tiers for CNV entries, there are a variety of search features that allow you to focus on identifying, for instance, functional studies that may have been performed to assess the consequences of a searched-for CNV.

Q: It looks as though the engine is optimised for CNV, but can it also work for fusions, inversions and translocations?

A: Mastermind allows you to search for evidence pertaining to known fusion pairs (NPM1 and ALK, for instance) using multi-parameter gene searching with “and” operator in addition to the “fusion” category of keywords. Later versions of Mastermind will allow for more flexible kayotype searching to uncover translocations and inversions leading to gene fusion events in a similar way as was illustrated for CNVs.

Q: Many users will be used to viewing a histogram for these SV, however the user interface seems to mirror searches for SNVs, is it possible to restructure the viewing panel according to a log scale histogram, with bars linking to relevant papers, as analysts may feel more comfortable with this format?

A: Yes. A conventional type of data visualization is planned for a future Mastermind release that will be more similar to the type of plot you describe.

Q: Can you search for HLA alleles including the HLA nomenclature for a high res. HLA NGS data. Including specific phenotypes.

A: We do not currently index the HLA nomenclatures for use in the context of tissue typing.

Q: Does the Mastermind CNV tool capture those CNVs from the large scale cancer genomics projects?

A: If the results of these CNV studies are described in the full-text, the answer is yes, they are captured in Mastermind. We are in the process of adding the supplemental data to our CNV indexing process as well. Please contact us at to bring to our attention any that are noted to NOT be captured so that we can address.

Q: Can I search for both losses and gains in one search?

A: Yes. Multiparameter searching for more than one CNV at a time is available including searching simultaneously for gain and loss of the same chromosomal element or region.

Q: Can you filter CNV search results by phenotype?

A: Yes, and indeed this is the recommended search strategy for instance when using Mastermind to uncover the most relevant evidence for chromosomal microarray results.

Q: Does MM take HPO term as an input for phenotype search? If the answer is no, can chance of adding this capability?

A: Yes. Phenotypes including HPO terms can be used as search parameters for filtering and prioritization.


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.