New algorithm could help investigate the genetic clues behind immunity

Scientists with UC San Diego's Jacobs School of Engineering and the Qualcomm Institute have developed a new gene prediction algorithm, called MINING-D, that could help researchers investigate the genetic clues behind the variation of symptoms shown in COVID-19 patients -; information that is key to creating a versatile and effective vaccine.

The findings and algorithm, which were published in PLOS Computational Biology on April 27, may give scientists a more comprehensive view of how the genes that form the foundation of our immune system create a personalized repertoire of antibodies to protect against invading pathogens. They may also shed light on why some people have a more effective immune response to an infection.

This study will be particularly helpful as dozens of groups begin testing potential COVID-19 vaccines, and see that the vaccine works on some people and not on others-;and the secret may be in the mutations in each individual's immune system. Without knowing the immune makeup of an individual, we won't be able to say why it worked or didn't work. MINING-D may help provide answers."

Pavel Pevzner, professor with UC San Diego's Department of Computer Science and Engineering and co-author on the paper

There are three groups of core immunoglobulin genes that are the building blocks of an individual's immune response: the variable (V), diversity (D) and joining (J) germline genes. MINING-D analyzes how those blocks, particularly the lesser-studied D gene, are shuffled and repackaged to create a large variety of antibodies. D genes play a critical role in creating the regions of antibodies that are responsible for recognizing pathogens.

"MINING-D will help researchers study mutations in D genes, which up until this point has been a challenge," said Vinnu Bhardwaj, the paper's lead author and a Ph.D. candidate with the Department of Electrical and Computer Engineering and Qualcomm Institute at UC San Diego. "Our initial study revealed that some variants of D genes are used more often than others in response to various infections. We hope this information will pave the way to unlocking clues about the role the D genes play in how difficult or easy it is for a patient to fight infection."

When a pathogen enters a healthy organism, it triggers an immune response that includes recombination of the germline genes and their random mutations. The process, which differs from individual to individual, results in roughly a billion antibodies circulating in each of us at any given moment. This personalized antibody repertoire is constantly changing to fight new infections.

"Our next step is to collaborate with leading immunogenomics experts at University of Louisville who are starting to sample antibody repertoires in patients with varying severity of COVID-19," said Yana Safonova, paper co-author and postdoctoral researcher in the Department of Computer Science and Engineering.

Safonova points out that, as in the case of flu, earlier studies showed a single mutation in a gene called IGHV1-69 resulted in an individual's reduced ability to recognize the flu virus and thus a failure to produce an immune response against it.

"Understanding similar genetic variations among COVID-19 patients may be the key to developing versatile vaccines that trigger the development of antibodies that recognize and neutralize the SARS-CoV-2 virus," Safonova said.

Source:
Journal reference:

Bhardwaj, V., et al. (2020) Automated analysis of immunosequencing datasets reveals novel immunoglobulin D genes across diverse species. PLOS Computational Biology. doi.org/10.1371/journal.pcbi.1007837.

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