Since 2007, we have been working on developing technologies and software tools to study immune repertoires. We have studied more than 40,000 samples and accumulated the most complete set of database on normal and patient repertoires. Based on deep knowledge and vast data, we have developed many clinical applications, for example: (1) Sharing Index, describing a person repertoire overlapping with a disease signature, therefore, can be used for disease diagnoses; (2) Delta Index, describing the repertoire turn over rate and can be used to monitor treatment; (3) Essential and Diversity Indexes, evaluating repertoire diversity and provide an estimate of a person’s immune reserve; (4) Response Index, evaluate potential of responding to immune therapies.
There are many technical challenges for sequencing immune repertoires. The method of library construction need to be inclusive, quantitative, and noise free. We have developed several multiplex PCR technologies (tem-PCR, arm-PCR, and dam-PCR) that allow us to amplify all 7 chains of T and B cell receptors from one sample, quantitatively. It also allowed us to study single cell to pair multiple chains of receptors and providing phenotype information at the same time. Sequencing immune repertoire is quite different from sequencing genomic DNA: Rather than re-sequencing a pubic genome, we perform de novo sequencing of private repertoires; the size of genome is known, while the size of repertoire universe is unknown; the genome is static, the repertoire is dynamic and changing every day; sequencing genome is to learn about genotype and physiology, pathways, sequencing repertoire is to learn about interactions with the environment, and is more about pathology and biomarkers. Genome sequencing can predict the future risks of having diseases; repertoire sequencing is trying to find out what our immune system is working on today.