Details

Autor(en) / Beteiligte

• 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

Titel

Rigorous benchmarking of T-cell receptor repertoire profiling methods for cancer RNA sequencing

Ist Teil von

• Briefings in bioinformatics, 2023-07, Vol.24 (4)

Ort / Verlag

England: Oxford University Press

Erscheinungsjahr

2023

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.