Enables Understanding of Viral Genome to Support Diagnostics Development

Bioinformatics is pivotal in the development of molecular and antigen test assays for viral respiratory diseases. Its use enables a wider and deeper understanding of the viral genome and its characteristics that might be relevant to designing effective diagnostic tools.

When looking at the genome of a virus, the sequence information embedded in the primer (or in the amplicon) is important to detection (or classification). There are various targets within the genome and the cell surface to target from an antibody perspective. There is a lot of information packaged into a single virion and it is important to select the optimal target for the intent of the assay, but bioinformatics is there to help hone in on that information.

https://doi.org/10.1038/s41374-021-00663-w

The Importance of High-Quality Genomic Data for Assay Design
The input of quality data and curation of the database for bioinformatics design is critical to the quality of the result. There are various publicly funded and publicly curated databases available. Their enormous scale creates an opportunity for errors to propagate. When finding the “in group” of targets and the “out group” to be exclusive to, making sure the records in the in group list and out group list are correctly labeled is important. Bioinformatics strategies and tools can specifically curate those databases to make sure the metadata labels are correct.

When checking this, we often find that there are errors in public databases. There are records that should be the inclusive group, but when searching for a given tax ID, some may be omitted because they’re not labeled at the appropriate taxonomic level.

We often see records that are in the taxa of interest, but their rank listed in the database is above or below the correct taxonomic level. The correct label might be captured in metadata fields that are not easily parsable. Scalable bioinformatics tools play a critical role in searching and parsing these metadata fields for potential information that would be beneficial for the assay design effort.

For more about the importance of “Point of Need” diagnostics like those for SARS-CoV-2, influenza, and RSV, listen to this episode of “Science Diction” from MRIGlobal.

Computational Modeling to Predict Assay Sensitivity and Specificity
Computational modeling is used to predict how sensitive and specific an assay will be. Bioinformatics tools enable virtual testing and optimization of assays against a range of viral strains, ensuring that they are effective across different virus variants.

Bioinformatics databases are now scaling to include an enormous amount of records. Manual manipulation of these vast databases is intractable, so the use of computational algorithms to automate this process is increasingly attractive.

Tools for Predicting Antigenic Epitopes
Predicting antigenic epitopes using bioinformatics tools is a critical step in designing antigen assays. These tools help in selecting antigens that are likely to elicit an immune response, thus enhancing the specificity and effectiveness of the assay.

Many tools are emerging to help us predict the actual structure of what a sequence will translate to in protein space. We can leverage that information in designing antigen-based assays that will interact with that structure in three-dimensional space. Through databases, we can align our targets to these protein sequences and then model those in three-dimensional space, understanding whether our intended antibody will interact with that molecule in a robust way. These tools are important in selecting those antigens to elicit that immune response, enhancing their specificity and effectiveness.

Bridging In Silico Prediction with Laboratory Testing
The transition from computational predictions to actual lab testing is crucial. This involves an iterative process where computational models are validated and refined based on lab testing results, ensuring that the final assay is both accurate and reliable.

Once we’ve used our bioinformatics tools, down selected our targets, tested them for their inclusivity and exclusivity in silico, and then have further down selected to those we believe are the best candidates to bring to testing in the laboratory, we work with our laboratory partners to validate those in the tube. There are several variables that in silico modeling has difficulty accounting for, making this an important step before validation and product launch.

For additional expertise on this topic, MRIGlobal’s Yvette Girard, MPH, Ph.D., Joe Russell, Ph.D., and Jennifer Stone, MS, hosted a free webinar on the development of rapid, accessible, and portable infectious disease diagnostics for seasonal respiratory diseases like influenza, RSV, and SARS-CoV-2. Watch the webinar recording at “Infectious Disease Diagnostics for Influenza, RSV and SARS-CoV-2.” You can also read about considerations for developing a disease diagnostic at “Six Stages to Developing a Novel Infectious Disease Assay.”

GETTING STARTED AT MRIGLOBAL

Contact MRIGlobal for further information about our work with infectious diseases. Through a multidisciplinary approach, we provide scientific and subject matter expertise for the development of medical countermeasures research against specific threats, while expanding and accelerating the delivery of high quality clinical diagnostic products.

To discuss how we can help your project be successful, contact us today.

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Bioinformatics in Assay Development

Enables Understanding of Viral Genome to Support Diagnostics Development