Overcoming the challenges of neoantigen identification
We deliver high quality, comprehensive genomic data and analytics to enable your neoantigen-based cancer vaccine development.
The first step of developing personalized vaccines is the identification of patient-specific neoantigens. These peptides can arise from anywhere in the genome, and methods for predicting which of these peptides will result in an efficacious vaccine are in early stages. That’s where we can help.
At Personalis, we’ve developed solutions to overcome the complexity of selecting neoantigens for personalized cancer vaccines. We provide whole exome and transcriptome sequencing, performed within timelines which make sense for vaccine development, as well as analytics to better inform your decisions:
Whole Exome and Transcriptome Sequencing
You need broad assays with comprehensive coverage, as existing cancer diagnostic panels are too limited for neoantigen detection (Garofalo et al., 2016). ACE ImmunoID is an analytically-validated whole exome and transcriptome sequencing platform using matched tumor and normal samples. Personalis exome capture methodology, based on ACE (Accuracy and Content Enhanced) Technology, augments sequencing coverage gaps to provide better detection of somatic mutations even in GC-rich regions (Patwardhan et al., 2015).
Neoantigen Identification Made Easy
Increasing your probability of designing a successful vaccine depends on accurate neoantigen identification. Personalis has developed a Neoantigen Discovery Analytics Engine and a Neoantigen Discovery Report, designed for use within the ImmunoID platform, to help you identify candidate neoantigens.
Clinical Trial Integration
Traditionally, whole exome and transcriptome sequencing has taken 6 weeks or more to perform. At Personalis, we’ve developed processes to reduce this to 14 calendar days, while still maintaining the highest quality standards.
ACE ImmunoID is an all-in-one immunogenomics platform. It combines our analytically validated ACE (Accuracy & Content Enhanced) Cancer Exome and ACE Cancer Transcriptome assays, in a tumor/normal configuration, to provide robust genomic data. Additionally, through our Neoantigen Discovery Engine, ACE ImmunoID provides analytics to elucidate the tumor’s neoantigen landscape.
ACE ImmunoID uses our patented ACE Technology which improves processes from nucleic acid extraction, through sequencing, to analytics. ACE ImmunoID stands apart by:
- Performing dual DNA/RNA extraction from FFPE samples: Maximizes the use of precious patient samples
- Providing augmented coverage to enhance neoantigen detection: Missed mutations lead to downstream inaccuracies in neoantigen predicitions
- Identifying neoantigens not only from SNVs, but also fusions and indels: Fusions and indels are a rich source of potential immunogenic peptides (Turajlic et al., 2017)
- Reporting HLA Class I and Class II typing: Validated in silico prediction from exome data to save time and sample
- Listing putative peptides which bind to the sample’s MHC Class I and Class II: Both are important in eliciting a sustained T-cell response as has been recently shown in first-human neoantigen-based vaccine trials (Sahin et al., 2017, Ott et al., 2017 )
ACE Cancer Exome
The ACE Cancer Exome assay provides high-coverage, high-accuracy sequencing of >20,000 genes, with improved coverage of > 1,400 cancer related genes, for superior neoantigen identification.
Gene-wide analysis of SYN1 (Figure 1, Panel B) shows the sequencing coverage provided by standard exome (blue regions) as well as the ACE-augmented coverage (green regions). ACE Cancer Exome coverage encompasses both the standard blue and the augmented green regions.
Positional analysis of peptide mutations and binding potential across the SYN1 genes (Figure 1, Panel A, highlighted region) indicates the number of predicted binding peptides that are captured in the augmented green region only (ACE supplementation)— these peptides would have been missed by the standard offering.
Figure 1. Superior coverage provided by the ACE Cancer Exome results in the identification of neoantigens that would have otherwise been missed by the standard exome.
ACE Cancer Transcriptome
The same accuracy and coverage are delivered with our ACE Cancer Transcriptome enrichment protocol. When compared to a standard exome enrichment protocol, the ACE Cancer Transcriptome shows more uniform and deeper coverage across the entire gene (see Figure 2). In addition, because we use the most current gene definitions, the ACE Cancer Transcriptome covers exons that are missing in the standard annotation and other exon capture methods (Figure 3).
Figure 2: Deeper, more even coverage. Samples were prepared with both a standard exome capture method (A) and the ACE Cancer Transcriptome protocol (B). Five exons of the BCR gene are shown. The ACE Cancer Transcriptome protocol shows deeper and more even coverage across all five exon regions.
Figure 3: Missing annotation. Samples were prepared with both a standard exome capture method (A) and the ACE Cancer Transcriptome protocol (B). Two exons of the AFF3 gene are shown. The standard exome capture method misses the second exon while the ACE Cancer Transcriptome protocol shows deeper and more even coverage of both.
Detecting tumor-specific neontigens and predicting those that will be presented is a complex problem. The scientists at Personalis developed the Neoantigen Discovery Engine to inform your translational research programs by consolidating molecular information thought to be critical for neoantigen prediction. The analytics engine provides an optional output from ACE ImmunoID, delivering comprehensive data for the evaluation of candidate neoantigens including:
- Identifies neoantigens resulting from SNVs, indels, and fusions
- Tumor mutational burden and neoantigen load
- Allelic fraction and gene expression of variants
- Phasing for allele–specific expression determination
- MHC Class I and MHC Class II peptide binding affinities (based on the sample’s HLA alleles)
Processes and systems to ensure your project is delivered within the agreed upon timelines:
One Point of Contact
- Dedicated project manager (PM) is your one point of contact for status updates and communication to Personalis
- PMs are PhD-level scientists with deep scientific and laboratory experience
Real-time Project and Sample Status
- Personalis’ Symphony Genomics Management System links LIMS, pipelines, databases, and other systems for real-time project status and sample-level tracking
- This allows your PM to ensure your project stays on track
Lock Down Assays and Pipeline Versions
- Symphony also locks down assays and analysis pipeline versions for the life of your study
- Additionaly, Symphony can globally accommodate reanalysis on updated pipelines, even after a study has closed
When you work with Personalis for neoantigen identification, you get a team of scientific and operational experts who are focused on your success.
Unlike other genomics providers that require multiple specimens, or the shipping of specimens to additional partner labs, ACE ImmunoID requires only one tumor sample and one normal sample—simplifying operations and decreasing risks.
ACE ImmunoID provides enhanced coverage of all coding genes to help you identify neoantigens that would otherwise be missed by standard exome assays. While we provide you with variant calls and raw data, we’ve also developed analytics for deeper insights into tumor biology.
Through our broad platform, advanced analytics, and project management we reliably deliver high quality genomic data to better inform your clinical and translational studies.