Loading…

Cross-Site Concordance Evaluation of Tumor DNA and RNA Sequencing Platforms for the CIMAC-CIDC Network

Whole-exome (WES) and RNA sequencing (RNA-seq) are key components of cancer immunogenomic analyses. To evaluate the consistency of tumor WES and RNA-seq profiling platforms across different centers, the Cancer Immune Monitoring and Analysis Centers (CIMAC) and the Cancer Immunologic Data Commons (CI...

Full description

Saved in:
Bibliographic Details
Published in:Clinical cancer research 2021-09, Vol.27 (18), p.5049-5061
Main Authors: Zeng, Zexian, Fu, Jingxin, Cibulskis, Carrie, Jhaveri, Aashna, Gumbs, Curtis, Das, Biswajit, Sanchez-Espiridion, Beatriz, Janssens, Sylvie, Taing, Len, Wang, Jin, Lindsay, James, Vilimas, Tomas, Zhang, Jianhua, Tokheim, Collin, Sahu, Avinash, Jiang, Peng, Yan, Chunhua, Duose, Dzifa Yawa, Cerami, Ethan, Chen, Li, Cohen, David, Chen, Qingrong, Enos, Rebecca, Huang, Xin, Lee, Jack J, Liu, Yang, Neuberg, Donna S, Nguyen, Cu, Patterson, Candace, Sarkar, Sharmistha, Shukla, Sachet, Tang, Ming, Tsuji, Junko, Uduman, Mohamed, Wang, Xiaoman, Weirather, Jason L, Yu, Jijun, Yu, Joyce, Zhang, Jianjun, Zhang, Jiexin, Meerzaman, Daoud, Thurin, Magdalena, Futreal, Andrew, Karlovich, Chris, Gabriel, Stacey B, Wistuba, Ignacio Ivan, Liu, X Shirley, Wu, Catherine J
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Whole-exome (WES) and RNA sequencing (RNA-seq) are key components of cancer immunogenomic analyses. To evaluate the consistency of tumor WES and RNA-seq profiling platforms across different centers, the Cancer Immune Monitoring and Analysis Centers (CIMAC) and the Cancer Immunologic Data Commons (CIDC) conducted a systematic harmonization study. DNA and RNA were centrally extracted from fresh frozen and formalin-fixed paraffin-embedded non-small cell lung carcinoma tumors and distributed to three centers for WES and RNA-seq profiling. In addition, two 10-plex HapMap cell line pools with known mutations were used to evaluate the accuracy of the WES platforms. The WES platforms achieved high precision (> 0.98) and recall (> 0.87) on the HapMap pools when evaluated on loci using > 50Ă— common coverage. Nonsynonymous mutations clustered by tumor sample, achieving an index of specific agreement above 0.67 among replicates, centers, and sample processing. A DV200 > 24% for RNA, as a putative presequencing RNA quality control (QC) metric, was found to be a reliable threshold for generating consistent expression readouts in RNA-seq and NanoString data. MedTIN > 30 was likewise assessed as a reliable RNA-seq QC metric, above which samples from the same tumor across replicates, centers, and sample processing runs could be robustly clustered and HLA typing, immune infiltration, and immune repertoire inference could be performed. The CIMAC collaborating laboratory platforms effectively generated consistent WES and RNA-seq data and enable robust cross-trial comparisons and meta-analyses of highly complex immuno-oncology biomarker data across the NCI CIMAC-CIDC Network.
ISSN:1078-0432
1557-3265
1557-3265
DOI:10.1158/1078-0432.CCR-20-3251