Rigorous benchmarking of T cell receptor repertoire profiling methods for cancer RNA sequencing
Rigorous benchmarking of T cell receptor repertoire profiling methods for cancer RNA sequencing
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 T cell receptor repertoires is generally referred to as TCR sequencing (TCR-Seq). However, the available TCR-Seq data is limited compared to 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 four cancer cohorts including both T cell rich and 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 to provide relative frequencies of clonotypes in T cell rich tissues and monoclonal repertoires. However, RNA-Seq-based TCR profiling methods have limited power in T cell poor tissues, especially in polyclonal repertoires of T cell poor tissues. The results of our benchmarking provide an additional appealing argument to incorporate the RNA-Seq into immune repertoire screening of cancer patients as it offers broader knowledge into the transcriptomic changes that exceed the limited information provided by TCR-Seq.
Nagareddy Anish、Pak Victoria M.、Burkhardt Amanda M.、Huang Yu-Ning、Nowicki Theodore Scott、Ribas Antoni、Abedalthagafi Malak S.、Miller Zachary、Peng Kerui、Alachkar Houda、Peng Dandan、Brito Jaqueline、Campbell Katie、Karlsberg Aaron、Mangul Serghei
Viterbi School of Engineering, University of Southern CaliforniaEmory Nell Hodgson School of Nursing, Emory University||Department of Epidemiology, Rollins School of Public Health, Emory UniversityDepartment of Clinical Pharmacy, School of Pharmacy, University of Southern CaliforniaDepartment of Clinical Pharmacy, School of Pharmacy, University of Southern CaliforniaDepartment of Pediatrics, Division of Pediatric Hematology/Oncology, University of California||Department of Microbiology, Immunology, & Molecular Genetics, University of CaliforniaDepartments of Medicine (Hematology-Oncology), Surgery (Surgical Oncology) and Molecular & Medical Pharmacology, University of CaliforniaGenomics Research Department, Saudi Human Genome Project, King Fahad Medical City and King Abdulaziz City for Science and Technology||King Salman Center for Disability Research||College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU)Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern CaliforniaDepartment of Clinical Pharmacy, School of Pharmacy, University of Southern CaliforniaDepartment of Clinical Pharmacy, School of Pharmacy, University of Southern CaliforniaDepartment of Quantitative and Computational Biology, Dana and David Dornsife College of Letters, Arts and Sciences, University of Southern CaliforniaDepartment of Clinical Pharmacy, School of Pharmacy, University of Southern CaliforniaDepartment of Medicine, Division of Hematology-Oncology, University of CaliforniaDepartment of Clinical Pharmacy, School of Pharmacy, University of Southern CaliforniaDepartment of Clinical Pharmacy, School of Pharmacy, University of Southern California
医学研究方法肿瘤学基础医学
Nagareddy Anish,Pak Victoria M.,Burkhardt Amanda M.,Huang Yu-Ning,Nowicki Theodore Scott,Ribas Antoni,Abedalthagafi Malak S.,Miller Zachary,Peng Kerui,Alachkar Houda,Peng Dandan,Brito Jaqueline,Campbell Katie,Karlsberg Aaron,Mangul Serghei.Rigorous benchmarking of T cell receptor repertoire profiling methods for cancer RNA sequencing[EB/OL].(2025-03-28)[2025-05-07].https://www.medrxiv.org/content/10.1101/2022.03.31.22273249.点此复制
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