abstract |
Methods and systems for determining a subject's likelihood of responding to a treatment by assessing the subject's cell-free DNA (cfDNA) sample include receiving sequence data gathered from sequencing the cfDNA sample, generating a feature matrix of values that correspond to synonymous and nonsynonymous mutations detected in the sequence data, and predicting, based on analysis of the feature matrix at a TMB prediction model, a tumor mutational burden (TMB) for a tissue of interest at the subject. The predicted TMB is evaluated to determine whether a set of criteria indicating a likely response to treatment is met. The set of criteria can include criterion(s) that are met when the predicted TMB is high, when the predicted TMB corresponds to a predicted tumoral heterogeneity indicative of homogeneous tissue, when the predicted TMB corresponds to a tumor fraction indicative of a positive responder, or any combination thereof. |