Personalis Inc

Personalis, Inc. is a provider of advanced genomic sequencing and analytics solutions to support the development of personalized cancer vaccines and other next-generation cancer immunotherapies.

Our patented ACE (Accuracy and Content Enhanced) Technology forms the foundation of all Personalis products. ACE Technology improves every individual step in the next-generation sequencing (NGS) process, from nucleic acid extraction, to sequencing assays, to data analytics. This makes it possible for us to achieve augmented coverage of difficult-to-sequence genomic regions that are missed with the use of conventional sequencing techniques.

Using this comprehensive approach, we provide genomic data of the highest quality and accuracy to help biopharma drive their immuno-oncology clinical and biomarker discovery programs, thus enabling the rational design and development of effective cancer immunotherapies.

Personalis was founded in 2011 as a Stanford University spin-out by a team of internationally-renowned NGS thought leaders consisting of John West (our CEO), Dr. Euan Ashley, Dr. Atul Butte, Dr. Russ Altman, and Dr. Michael Snyder. Our headquarters – housing our CLIA-certified, CAP-accredited laboratory – is located in Menlo Park, CA.

Our patented ACE® (Accuracy and Content Enhanced) Technology is the foundation of the Personalis® NeXT Platform™ and all our proprietary products. ACE improves processes from nucleic acid preparation, to sequencing, to analytics for superior sequencing results.

By applying our ACE Technology to all ~20,000 genes, our NeXT Exome provides deeper, more uniform coverage at high depths than standard assays. Specifically, the NeXT Exome outperforms conventional exome assays by enhancing coverage across coding regions and supplementing, via a novel, proprietary probe design, more complex areas in the genomic architecture such as GC-rich content.

The Personalis solution provides targeted sequencing to augment coverage gaps present in typical exomes, thus reducing the likelihood of the non-detection of potentially significant somatic variants present in patients’ tumors. For example, in a paper published by van Buuren et al. in OncoImmunology, the PRDX5 gene is reported to harbor variants that result in immunogenic epitopes, the part of an antigen that can be recognized by the immune system. Figure 1 highlights the superior, uniform coverage of exonic regions achieved by the ACE-enabled exome (green plus blue) compared to the most widely-used standard exomes (blue) for clinical and translational oncology research. Variants residing in green regions (red rectangles) would likely be missed with a standard exome platform.

In addition to ACE augmentation, the unique NeXT Exome probe design also facilitates the enhanced targeting of areas of the genome that are particularly pertinent to modern precision oncology research and clinical applications including the HLA genes, exome-wide MSI-related loci, as well as oncoviral genomes. This enables the more accurate characterization of established and investigational oncology biomarkers in every tumor sample processed with the NeXT Exome.

The innovative assay design also incorporates boosted coverage of 247 targeted therapy cancer-related genes. Going to a sequencing depth of >1,000X in these genes enables the clinical-grade sensitivity and specificity that’s required to identify potentially clinically-significant small and structural variants for clinical diagnostic applications such as therapy selection and clinical trial matching.

Many clinical studies depend on tissue archives that have been fixed using FFPE procedures. This preservation process makes it difficult to obtain a pure sample and often leads to RNA degradation. To overcome this challenge, Personalis has developed our NeXT Transcriptome with an exome-capture protocol, again based on our ACE Technology, that allows us to produce consistently high-quality transcriptome sequencing results from FFPE samples and other challenging sample types.

Our enrichment protocol directly selects for transcripts using the optimized ACE capture probes, eliminating background and focusing the sequencing on regions of interest. Sequencing using the ACE-enabled transcriptome protocol demonstrated that >84% of the bases mapped within the coding region of the RNA (Figure 2). Thus, the ACE approach results in high quality data and low off-target reads, particularly impressive when compared to other conventional approaches such as ribosomal RNA (rRNA)-depletion-based methodologies.