The human body is able to defend itself from a wide array of invading pathogens through innate and adap-tive immune responses. The adaptive immune system possesses the extraordinary ability to generate specific defenses against never before seen pathogens. T-cells (and B-cells) are able to generate unique recep-tors through a process of combinatorial joining of DNA and random nucleotide addition, known as VDJ re-combination. Thus, every immature T-cell contains a unique receptor DNA sequence not present in any other cell in the human body. T-cells whose receptors are able to target an invading pathogen specifically are then given signals to divide.
With this phenomenon in mind, we have the ability to track the rise and fall of T-cell activity by identifying unique receptors via High Throughput Sequencing. Changes in fraction of T-cells in a blood sample dis-playing a particular receptor sequence indicate chang-es in activity of the immune system specific to a path-ogen. Although these experiments are in their infancy, one day we hope to be able to track the status of chronic autoimmune disorders and identify exact ill-nesses based on receptor sequence alone. One appli-cation of this methodology is the tracking of blood can-cers and sensitive detection of cancer reoccurrence.
To enable the discovery of disease specific receptor sequences, I have developed the UCSC TCR-B Browser. The Browser is a web-based tool that allows researchers to quickly compare the fractions of unique receptor sequences between samples. It also allows researchers to identify specific receptors that may be disease associated and allows them to track their rela-tive rise and fall over time. The tool is particularly use-ful for tracking of blood cancers, but is also applicable to tracking the disease state in a person affected by autoimmune disorders.
This demo shows the comparison view for 3 samples only. Adding new samples or filtering the existing samples requires connection to a backend database that is not feasible to include in this demo.
