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Estimating tumor mutational burden from RNA-sequencing without a matched-normal sample
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DOI：10.1038/s41467-022-30753-2.png)
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Abstract
En 中文
The identification of somatic point mutations in tumor samples is of high clinical value, such as for the development of targeted therapies. Here the authors develop a machine learning pipeline for detecting somatic point mutations from RNA sequencing without a matched-normal sample, and utilize the model's prediction for computing the tumor mutational burden. Detection of somatic mutations using patients sequencing data has many clinical applications, including the identification of cancer driver genes, detection of mutational signatures, and estimation of tumor mutational burden (TMB). We have previously developed a tool for detection of somatic mutations using tumor RNA and a matched-normal DNA. Here, we further extend it to detect somatic mutations from RNA sequencing data without a matched-normal sample. This is accomplished via a machine-learning approach that classifies mutations as either somatic or germline based on various features. When applied to RNA-sequencing of >450 melanoma samples high precision and recall are achieved, and both mutational signatures and driver genes are correctly identified. Finally, we show that RNA-based TMB is significantly associated with patient survival, showing similar or higher significance level as compared to DNA-based TMB. Our pipeline can be utilized in many future applications, analyzing novel and existing datasets where only RNA is available.
Keywords:
SOMATIC MUTATIONS
CTLA-4 BLOCKADE
CANCER
DATABASE
HETEROGENEITY
SIGNATURES
DISCOVERY
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