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Optimizing the evaluation of gene-targeted panels for tumor mutational burden estimation
1Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
Scientific Reports
|October 27, 2021
Summary
Angular distance offers a more accurate method for evaluating gene-targeted panels used in tumor mutational burden (TMB) estimation compared to the R-squared value. This new approach provides a more objective assessment of panel performance in cancer research.
Area of Science:
- Oncology
- Genomics
- Biostatistics
Background:
- Whole exome sequencing (WES) is the standard for tumor mutational burden (TMB) measurement.
- Gene-targeted panels offer a cost-effective alternative for TMB estimation in clinical trials.
- Current evaluation methods using R-squared may overestimate panel performance due to TMB data distribution.
Purpose of the Study:
- To introduce and validate angular distance as a superior metric for evaluating gene-targeted panels.
- To compare the performance of angular distance against the conventional R-squared value.
- To provide a more objective and sensitive method for assessing TMB estimation accuracy.
Main Methods:
- In silico analysis comparing R-squared and angular distance metrics.
- Evaluation of panel performance across varying panel sizes (0.5 Mb to 6 Mb).
- Assessment of metric sensitivity to TMB distribution, including hypermutated and non-hypermutated datasets.
Main Results:
- R-squared values plateau after 0.5 Mb panel size, failing to adequately characterize performance.
- Angular distance remains sensitive to panel size changes up to 6 Mb.
- Angular distance shows consistent results across different cancer types and mutation profiles, unlike R-squared.
Conclusions:
- Angular distance is a more objective and logical metric than R-squared for evaluating gene-targeted panels.
- This method provides a more reliable assessment of TMB estimation accuracy.
- Angular distance is crucial for comparing diverse gene panels in cancer research.
