Shoreline’s Immuno-bioinformatics will be a five-week hands on computer class that will demonstrate ways in which immunologists use bioinformatics. Topics will include receptor profiling, vaccine development, and reagent / drug development as described below.
Receptor Profiling - Receptor Profiling, made possible by high-throughput, massively parallel, DNA sequencing is used to study the immune response in disease and to antigens and vaccines. Common methods involve sequencing RNA from immune cells in blood and other tissues. After RNA is converted to cDNA, synthetic DNA primers that flank the common regions of V-gene and J-gene segments are used to amplify DNA molecules containing antibody (BCR; B-cell receptor) or T-cell receptor (TCR) sequences. As each molecule is sequenced independently, the collection of sequences obtained from an experiment, or assay, measures the ensemble of receptor sequences that were present in a sample. Bioinformatics tools are then used to determine the frequency of sequences as a way to measure if specific sequences from the receptors are being selected for as part of an immune response.
Vaccine Development - BCRs and TCRs bind to specific regions of molecules, commonly proteins. These regions, called epitopes, can be use to stimulate the immune system in short and long-term ways to create vaccines that protect us from disease and fight cancer. The biotechnology industry is deeply interested in developing new kinds of vaccines for viral and other diseases including cancer. In vaccine development, bioinformatics is used to predict epitopes from protein sequences and population responses to potential vaccines made from those epitopes.
Reagent / Drug Development - For many years, antibodies have been developed to be used as reagents in many kinds of assays. Due to the specificity of the antibody / antigen interaction, antibodies can be excellent detection reagents. In biotechnology, antibodies are developed for diagnostic and research applications. As noted above, they and TCRs are also developed into drugs. In cancer, antibodies can be used to bind to cancer cells to simulate a tumor destroying immune response. Antibodies can also block interactions between cells that help cancers grow. Hybrids of antibodies and TCRs (CAR-T technology) are also used direct immune cells to tumors in highly targeted ways. The bioinformatics related to developing diagnostics and reagents can use receptor profiling, epitope analysis, and other methods. In diagnostic and reagent development, statistical analyses are also important because data from many tests need to be analyzed overtime to ensure assay reproducibility and validity.
Most of the class time will be spent working with data and reviewing how the results of analyses measure the immune system and reinforce immunology concepts. In short, the data show the biology. Authentic data sets from scientific publications will be used in conjunction with web-based software systems that are used by scientists in industry and academia for receptor profiling and vaccine development. Such systems utilize many kinds of bioinformatics tools that perform specific data manipulations and analyses. Using the tools in organized systems makes it possible to learn how a tool its used to explore an aspect of the science without the distraction of how to set up the tool for use.
While the first part of the hands on experience focuses on the scientific end points of immuno-bioinformatics, it does not provide a full appreciation of all of the steps needed to understand the data and how data collection and quality can impact the results. In the case of receptor profiling this is particularity important as the process for collecting the data involves many steps that can produce artifacts if they are not performed well, or if the data are not processed with this understanding in mind. Hence, in the last part of the course will utilize cloud computing and command line tools to conduct the initial steps of a profiling experiment.
Through the class experience students will be exposed to several aspects of bioinformatics from data analysis to data processing to gain a deep appreciation of the power and richness of the immune system.