For the first time, researchers sequenced the human immune system, which is billions of times larger than the human genome. In a new study, published in nature of the human vaccine project, scientists have set out a key part of this vast and mysterious system – the genes encoding the circulating receptor of the B-cell receptor.
Along with these receptors in adults and infants, scientists have found surprising overlaps that could provide potential new vaccine targets for vaccines and therapists working in the populations. As part of a multi-year initiative, this work aims to identify the genetic basis of people's ability to react and adapt to a wide range of diseases.
Led by scientists at the Vanderbilt University Medical Center and the San Diego supercomputer center, this progress is made possible by the merger of biological research with powerful border supercomputers. While the human genome project consistently determines the human genome and leads to the development of new genomic tools, it does not deal with the size and complexity of the human immune system.
"The continuing challenge in the field of human immunology and vaccine development is that we do not have exhaustive reference data on what the normal healthy human immune system looks like," says James E. Crowe, director of the Vanderbilt Center of the University Medical Center in Vanderbilt, senior author of the new document that was published online in Bulgaria nature on February 13. "Before the present era, people assumed that it would be impossible to do such a project because the immune system is theoretically so large, but this new book shows that it is possible to define a large part because the size of the repertoire of the B cell receptor every person is unexpectedly small. "
The new study specifically looks at a part of the adaptive immune system, the circulating B-cell receptors, which are responsible for the production of antibodies that are considered to be a major determinant of immunity in humans. The receptors randomly select and bind gene segments, forming unique sequences of nucleotides known as receptor "clones". Thus, a small number of genes can lead to an incredible variety of receptors allowing the immune system to recognize almost every new pathogen.
By conducting leukopheresis in three separate adults, the researchers cloned and sequenced up to 40 billion cells to stack combinations of gene segments containing the circulating B cell receptors – achieving depth of sequence that had never before been done. They also consistently have umbilical cord blood from three babies. The idea was to gather huge amounts of data for several individuals, not the traditional model to collect just a few data points for many people.
"The overlap of antibody sequences between individuals is unexpectedly high," Crow explains, "even showing some identical antibody sequences between adults and babies at birth." Understanding this interaction is key to identifying antibodies that can be targeted for vaccines and treatments that work more universally among the population.
The main question is whether shared sequences between individuals are the result of chance rather than the result of some common common biological or environmental factors. To cope with this problem, the researchers developed a synthetic B-cell receptor and found that "experimentally observed overlapping is significantly greater than what would be expected by accident," said Dr. Robert Sinkovits of the San Diego Supercomputer Center University of California, San Diego.
As part of a unique consortium created by the human vaccine project, San Diego's supercomputer center has applied its considerable computational power to work with multiple terabytes of data. The basic principle of the project is the merging of biomedicine and advanced computer technologies. "The human vaccine project allows us to study problems on a larger scale than would normally be possible in a laboratory, and it also brings together groups that can not normally collaborate," Sinkovic says.
Cooperative work continues to expand this study, including: sequencing other areas of the adaptive immune system, the T cell repertoire; adding additional demographic indicators such as super-centers and international populations; and applying algorithms run by the AI to further retrieve the data sets for insights. The goal is to continue to question the shared components of the immune system to develop safer and more targeted vaccines and immunotherapies that work among the population.
"Due to recent technological advances, we now have an unprecedented opportunity to use the power of the human immune system to fundamentally transform human health," said Wayne Coff, chief executive officer of the Human Vaccine Project. "The decoding of the human immune system is essential to address the global challenges of infectious and non-infectious diseases, from cancer to Alzheimer's disease to the pandemic influenza." – Generation of health products through the approximation of genomics and immune monitoring technologies with machine training and artificial intelligence .
The new book, "High Frequency of Shared Clones in Human B Receptor Receptors," was published online nature on February 13, 2019, and will appear in the print edition of February 21, 2019.
A mosaic-like gene deletion and a pattern of duplication that formed the immune system were discovered
High frequency of shared clones in the human B cell receptor repertoire, nature (2019). DOI: 10.1038 / s41586-019-0934-8, https://www.nature.com/articles/s41586-019-0934-8
Human Vaccine Project
Decoding the Human Immune System (2019, February 13)
withdrawn on 13 February 2019
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