We have made updates to the Mastermind Genomic Search Engine interface to streamline the user experience and prepare the way for some exciting new developments – the first of which is the ability to search by Human Phenotype Ontology (HPO) terms!

Key features of the user interface changes:

Combined Search Fields: This single search field simplifies searching by allowing you to type what you need without having to navigate between different fields to enter your query.

Quick-Start Typing: Simply type what you want and Mastermind provides suggestions across genes, variants, diseases, phenotypes, and keywords, making it easier to realize the possibilities offered for your search.

Unified Search Mode: We’ve incorporated Mastermind’s “advanced search” mode (which allowed for multi-parameter and free-text searching), making it faster and easier to refine your search without needing to decide ahead of time what kind of search you’ll need. For instance, after you’ve added a gene, Mastermind automatically switches to advanced mode when you begin typing another.

Phenotypes are Here!

We are proud to announce the addition of Human Phenotype Ontology (HPO) terms to Mastermind. The ability to search by phenotype gives you even more power to discover which genes in patient sequencing data are most likely to be relevant based on empirical data in the medical literature.
When you search for a clinical phenotype or phenotypes, the Mastermind results page will show contextual sentence fragments from articles mentioning those phenotypes, enabling you to quickly move through matched results to narrow in on meaningful articles for further investigation. You can view them in the “Full-Text Matches” pane of the detail page by selecting “Phenotypes only” (or “All matches”). This helps you filter and prioritize the most relevant papers when you have a patient or biological pathway with known phenotypes but unknown disease.

This update to Mastermind was announced at ASHG this year in Houston and got rave reviews from attendees at the Genomenon booth. Here are some example search queries that will give you a sense for how this new capability can be applied.

USE CASE #1: Search for genes and articles related to a specific phenotype

PHENOTYPE SEARCH TERM: Axillary Freckling

GENE RESULTS:

NF1 RESULTS:

COMMENTS:
Axillary freckling is a common manifestation of neurofibromatosis – a disease of non-neuronal cells of the nervous system (known as Schwann cells) that surround neurons. Neurofibromatosis is caused by mutations in NF1 (or NF2) leading to numerous small to very large neurocutaneous and visceral nerve-cell tumors. Other symptoms of neurofibromatosis (or NF) include cafe-au-lait macules on the skin – usually several.

MASTERMIND HIGHLIGHT:
This search by phenotype delves into the full text and prioritizes the genes by article count and the articles by term count. Among the top-ranked genes is the NF1 gene. If this gene-phenotype association was unknown to you, searching Mastermind for this phenotype would have prioritized it for you and led you directly to the articles that demonstrate the link. Clicking on this will display the NF1 gene and the phrase “axillary freckling” in the sentence fragments from prioritized articles citing this association. Using only one phenotype is recommended ONLY if the phenotype is very specific and a gene-phenotype association is something you wish to investigate.

USE CASE #2: Search for genes and articles related to specific phenotypes

PHENOTYPE SEARCH TERM: Aortic Aneurysm and Arachnodactyly

GENE RESULTS:

FBN1 RESULTS:

COMMENTS:
Arachnodactyly and aortic aneurysm are hallmarks of Marfan syndrome. Other features include tall stature, long arm span, ectopia lentis, heart murmurs and pectus carinatum. It is caused by mutations in the fibrillin or FBN1 gene, but also has to do with TGFRB and ELN.

MASTERMIND HIGHLIGHT:
This search using multiple phenotypes allows users to see the toggle between “and” and “or” for multi-parametric searching, and demonstrates how to tailor a search to identify papers that may discuss a less-common feature of the disease (for instance, ectopia lentis) if this term were to be added to the search above.

USE CASE #3: Search for genes and articles related to complex phenotypes in a patient with a putative genetic syndrome

SEARCH TERMS: Sleep Disturbance and Delayed Speech and Language Development and Brachycephaly and Behavioral Abnormality and Brachydactyly

GENE RESULTS:

RAI1 RESULTS:

COMMENTS:
Smith-Magenis syndrome is caused by mutations in RAI1 and has effects on multiple body systems. Among the features of this disease are sleep disturbances and brachycephaly and brachydactyly and behavioral abnormalities and delayed speech. These features are individually not very specific for any one syndrome, but together are characteristic of Smith-Magenis Syndrome. Other features include a down-turned mouth and prominent jaw.

MASTERMIND HIGHLIGHT:
Entering all of these features using the boolean “and” operator returns RAI1 near the top of the list (below the gene SMS, which is a false positive for Smith Magenis Syndrome, also abbreviated as SMS). This false positive demonstrates the sensitivity of Mastermind as a tool for facilitating manual curation and literature review. The contextual sentence fragments in the interface make it easy to recognize the most relevant results quickly. The result for RAI1 with this list of phenotypes demonstrates the powerful and immediate insight gained from the use of Mastermind’s phenotype search capability.

The Wrap-Up

We are very proud to bring this new search interface and phenotype support to Mastermind, and know you will find it useful. We recognize how important using phenotypes is in clinical practice, especially for challenging genetics cases. This update is a milestone on our path of constant improvement, and lays the groundwork for more to come. What’s next? Stay tuned!

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