The Human Immune System Decoded | Technology Networks https://www.technologynetworks.com/immunology/news/the-human-immune-system-decoded-315418
For the first time ever, researchers are comprehensively sequencing the human immune system, which is billions of times larger than the human genome. In a new study published in Nature from the Human Vaccines Project, scientists have sequenced a key part of this vast and mysterious system — the genes encoding the circulating B cell receptor repertoire.
Decoding the human immune system is central to tackling the global challenges of infectious and non-communicable diseases, from cancer to Alzheimer’s to pandemic influenza. This study marks a key step toward understanding how the human immune system works, setting the stage for developing next-generation health products through the convergence of genomics and immune monitoring technologies with machine learning and artificial intelligence.”
The new study specifically looks at one part of the adaptive immune system, the circulating B cell receptors that are responsible for the production of antibodies that are considered the main determinant of immunity in people. The receptors randomly select and join gene segments, forming unique sequences of nucleotides known as receptor “clonotypes.” In this way, a small number of genes can lead to an incredible diversity of receptors, allowing the immune system to recognize almost any new pathogen.
Conducting leukapheresis on three individual adults, the researchers cloned and sequenced up to 40 billion cells to sequence the combinations of gene segments that comprise the circulating B cell receptors — achieving a depth of sequencing never before done. They also sequenced umbilical cord blood from three infants. The idea was to collect a vast amount of data on a few individuals, rather than the traditional model of collecting only a few points of data on many.
“The overlap in antibody sequences between individuals was unexpectedly high,” Crowe explains, “even showing some identical antibody sequences between adults and babies at the time of birth.” Understanding this commonality is key to identifying antibodies that can be targets for vaccines and treatments that work more universally across populations.
A central question was whether the shared sequences across individuals were the result of chance, rather than the result of some shared common biological or environmental factor. To address this issue, the researchers developed a synthetic B cell receptor repertoire and found that “the overlap observed experimentally was significantly greater than what would be expected by chance,” says Robert Sinkovits, Ph.D., of the San Diego Supercomputer Center at the University of California, San Diego.
As part of a unique consortium created by the Human Vaccines Project, the San Diego Supercomputer Center applied its considerable computing power to working with the multiple terabytes of data. A central tenet of the Project is the merger of biomedicine and advanced computing. “The Human Vaccines Project allows us to study problems at a larger scale than would be normally possible in a single lab and it also brings together groups that might not normally collaborate,” Sinkovits says