Technologies for neoantigen discovery are critical for the development of personalized cancer therapies and neoantigen-based biomarkers. Precision neoantigen discovery entails comprehensive detection of tumor-specific genomic variants and accurate prediction of MHC presentation of epitopes originating from such variants. Our ImmunoID NeXT Platform® enables a comprehensive survey of putative neoantigens by combining highly sensitive exome- scale DNA and RNA sequencing with the NeoantigenID™ analytics engine.
The NeoantigenID analytics engine flows seamlessly from biological samples to neoantigen prediction (Figure 4), as follows:
- First, the sequencing data from the NeXT Exome and Transcriptome are run through the NeXT DNA and RNA pipeline in order to identify tumor-specific small variants and fusions.
- Highly accurate germline in silico HLA typing is performed, followed by somatic mutation and allele-specific loss of heterozygosity (LOH) detection in the HLA genes.
- Tumor-specific small variants and fusions are combined with the patient HLA types and gene expression information to predict neoantigens using our internally-developed Systematic HLA Epitope Ranking Pan Algorithm (SHERPA™).
- SHERPA has been integrated into Personalis’ NeoantigenID analytics engine along with additional secondary metrics that enable further prioritization of the predicted putative neoantigen candidates.
- Accurate neoantigen prediction with SHERPA enables the determination of candidate neoantigens for rapid development of personalized cancer therapies, as well as facilitating the generation of neoantigen burden-based composite biomarkers such as the Personalis NEOantigen Presentation Score (NEOPS) that can potentially better predict response to immunotherapies.
Figure 4: NeoantigenID Analytics Engine
The NeoantigenID reporting output consists of:
- A list of all putative neoantigens and their comprehensive characterization
- In silico HLA genotyping, as well as somatic alterations impacting HLA genes incuding SNVs, indels, and HLA LOH
- A NeoantigenID Summary Report containing NEOPs, neoantigen burden, and tumor mutational burden (TMB).