An integrated transcriptomic and proteomic approach to antibody sequencing and repertoire characterization

Period of Performance: 02/16/2017 - 01/31/2018

$388K

Phase 2 SBIR

Recipient Firm

Digital Proteomics, LLC
LA JOLLA, CA 92037
Principal Investigator

Abstract

Antibodies are ideal drug candidates due to their high specificity for target molecules. Monoclonal antibodies represent one of the fastest growing segments of the drug market, however, recent attention has focused on polyclonal antibodies and monoclonal mixtures to reduce the opportunity for a disease to become drug resistant. Polyclonal antibodies sampled from disease survivors or immunized hosts offer a wealth of new drug candidates. Current pipelines for investigating the immune response rely on hybridoma technology, which is time- ?consuming and does not come close to mimicking the diversity of antibodies present in the organism. Next generation sequencing of B- ?cells can deeply interrogate the immune response, however, this technology falls short of providing insight into the best antibody drug candidates. We propose the development of Valens- ?Poly, which will integrate mass spectrometry- ?based proteomics data with next generation sequencing of B- ?cells, an emerging field called immunoproteogenomics. By interrogating the immune response at the protein- ?level, Valens- ?Poly will be able to rank antibody sequences based on their abundance, which is a proxy for specificity to the antigen of interest. It is impossible to sequence all memory B- ?cells in a host organism, therefore the antibody sequences reported would only represent a small fraction of the antibodies that could be present. Using our patented spectral network approach, pioneered in our monoclonal antibody sequencing tool, Valens, we will be able to recover complementarity- ?defining regions (CDRs) of antibodies even when the B- ?cell was not captured for next generation sequencing. Finally, we will characterize the broad spectrum of antibodies produced as part of the immune response, called the antibody repertoire. Identifying changes in germline gene usage and tracking clone abundance and lineage in response to immunization or across patients is an important component of characterizing diseases and guiding drug discovery.