Abstract: The disclosure provides methods for predicting surface-presenting peptides using binding and surface-presentation characteristics. The method can include accessing a trained machine-learning model that is configured to generate an output that indicates an extent to which the one or more expression levels and the one or more peptide-presentation metrics are related in accordance with a population-level relationship between expression and presentation. For each peptide of the set of peptides for a tissue sample, a score can be determined using the machine-learning model and genomic and transcriptomic data corresponding to the peptide. The score is predictive of whether a corresponding peptide is a surface-presenting peptide that binds to an MHC molecule and is presented on a cell surface.

Abstract: Methods for generating a composite biomarker that identifies a predicted level of responsiveness of a subject to a particular type of an immunotherapy treatment is provided. The method can include generating genomic metrics that represent one or more characteristics corresponding to one or more DNA sequences. The method can also include generating transcriptomic metrics represent one or more characteristics corresponding to a set of peptides that are translated from a corresponding RNA sequence of the one or more RNA sequences. The method can also include generating a composite biomarker score derived from the set of genomic metrics and the set of transcriptomic metrics. The method can also include determining, based on the composite biomarker score, a predicted level of responsiveness of the subject to a particular type of an immunotherapy treatment.