Integrated RNA and DNA sequencing improves mutation detection in low purity tumors.
Bottom Line: In simulation, the integrated DNA and RNA model outperformed the DNA-WES only model.RNA provided greater mutation signal than DNA in expressed mutations.Compared to earlier studies on this cohort, UNCeqR increased mutation rates of driver and therapeutically targeted genes (e.g. PIK3CA, ERBB2 and FGFR2).
Affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA email@example.com.Show MeSH
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Mentions: To validate the superior performance of integrated DNA-WES and RNA-seq mutation detection (UNCeqRMETA) over DNA-WES only detection (UNCeqRDNA), tumor and germline whole genome DNA sequencing (DNA-WGS) was used as an independent measure of truth for evaluating DNA-WES and RNA-seq mutation detections. Following a published validation procedure (4), mutation detections were interrogated in patient-matched DNA-WGS to determine if a mutation detection was a true positive, that is present in the tumor specimen and absent from the germline specimen, or false positive, that is absent from the tumor specimen or present in the germline specimen. For each mutation model, true positives and false positives were summed at each discrimination threshold (e.g. P-value) to generate a performance curve by which true positive rates could be compared at the same false positive rates (see methods for further description). These curves demonstrated that UNCeqRMETA achieved overall superior performance than UNCeqRDNA (difference in area under the curve, P < 0.01) and at fixed false positive thresholds (250, 500 and 1000), thus, validating the result from simulated tumor genomes (Figure 2). Therefore, in real tumor sequencing, integrated DNA and RNA mutation detection by UNCeqRMETA outperformed DNA-only mutation detection.
Affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA firstname.lastname@example.org.