Analysis Pipeline to Investigate Diversity and Dynamics of Next-Generation Sequencing--Based T Cell Repertoire Data

• Activity Number: 356
• Type: Contributed
• Date/Time: Tuesday, August 2, 2016 : 10:30 AM to 12:20 PM
• Sponsor: Biometrics Section
• Author(s): Li Zhang* and Jason Cham and Nadeem Sheikh and Lawrence Fong
• Companies: University of California at San Francisco and University of California at San Francisco and Dendreon Corporation and University of California at San Francisco
• Keywords: Diversity ; Dynamics ; Differential Testing ; Next generation sequencing ; Analysis Pipeline ; T-cell receptor

Abstract

Cancer immunotherapy has demonstrated significant clinical activity in many cancers. T-cells represent a crucial component of the adaptive immune system. The part of the T-cell responsible for antigen-specific recognition is the T-cell receptor (TCR). Next generation sequencing (NGS) of the TCRs can be used as a platform to quantitate T cell clonotypes. We propose a "3D" analysis pipeline, consisting of assessing Diversity of T-cell repertoire, evaluating Dynamics of TCR sequencing across the time course or among different biological compartments, and performing Differential testing of the abundance of each clone between pre- and post-treatment. Applying the pipeline to a real example of prostate patients who received FDA-approved immunotherapy, we are able to detect the changes in TCR sequence frequency and diversity which demonstrates the treatment affects the TCR repertoire in the blood and increases the TCR diversity in the prostate tissue. We believe that the establishment of this analysis pipeline will provide researchers with a guideline and parameters to consider for future studies using NGS-based TCR repertoire profiling.