학술논문
Rigorous benchmarking of T-cell receptor repertoire profiling methods for cancer RNA sequencing.
Document Type
Article
Author
Peng, Kerui; Nowicki, Theodore S; Campbell, Katie; Vahed, Mohammad; Peng, Dandan; Meng, Yiting; Nagareddy, Anish; Huang, Yu-Ning; Karlsberg, Aaron; Miller, Zachary; Brito, Jaqueline; Nadel, Brian; Pak, Victoria M; Abedalthagafi, Malak S; Burkhardt, Amanda M; Alachkar, Houda; Ribas, Antoni; Mangul, Serghei
Source
Subject
*RNA sequencing
*T cells
*TUMOR antigens
*T cell receptors
*EARLY detection of cancer
*CANCER research
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Language
ISSN
1467-5463
Abstract
The ability to identify and track T-cell receptor (TCR) sequences from patient samples is becoming central to the field of cancer research and immunotherapy. Tracking genetically engineered T cells expressing TCRs that target specific tumor antigens is important to determine the persistence of these cells and quantify tumor responses. The available high-throughput method to profile TCR repertoires is generally referred to as TCR sequencing (TCR-Seq). However, the available TCR-Seq data are limited compared with RNA sequencing (RNA-Seq). In this paper, we have benchmarked the ability of RNA-Seq-based methods to profile TCR repertoires by examining 19 bulk RNA-Seq samples across 4 cancer cohorts including both T-cell-rich and T-cell-poor tissue types. We have performed a comprehensive evaluation of the existing RNA-Seq-based repertoire profiling methods using targeted TCR-Seq as the gold standard. We also highlighted scenarios under which the RNA-Seq approach is suitable and can provide comparable accuracy to the TCR-Seq approach. Our results show that RNA-Seq-based methods are able to effectively capture the clonotypes and estimate the diversity of TCR repertoires, as well as provide relative frequencies of clonotypes in T-cell-rich tissues and low-diversity repertoires. However, RNA-Seq-based TCR profiling methods have limited power in T-cell-poor tissues, especially in highly diverse repertoires of T-cell-poor tissues. The results of our benchmarking provide an additional appealing argument to incorporate RNA-Seq into the immune repertoire screening of cancer patients as it offers broader knowledge into the transcriptomic changes that exceed the limited information provided by TCR-Seq. [ABSTRACT FROM AUTHOR]