Next-generation Sequencing Research Solutions Overview

With Personalis’ extensive suite of advanced genomics and analytics offerings, drug developers can maximize the potential of their pipeline. We offer broad-content next-generation sequencing (NGS) assays that enable the generation and interpretation of high-quality molecular data to drive discovery, preclinical, clinical and translational research programs across many disease areas.

Personalis’ DNA and RNA NGS capabilities can assist in gaining deeper insights into a drug candidate’s mechanism of action and associated mechanisms of resistance, while also enabling the exploration of rational drug combinations at an expansive scale and competitive cost-effectiveness. Every step in the process from nucleic acid extraction and library preparation through to sequencing is performed in our CLIA-certified/CAP-accredited laboratory, with downstream analysis performed using our framework of advanced algorithms.

ACE Research Exome

Using our patented Accuracy and Content Enhanced (ACE) Technology, the ACE Research Exome outperforms conventional exome assays by augmenting coverage across intronic and difficult-to-sequence regions (including regions of high-GC content) of >8,000 biomedically-important genes, including >1,400 cancer-related genes. The application of this technology ensures the delivery of more complete and uniform coverage of targeted gene regions; resulting in the more accurate and reliable capture of both germline and somatic single-nucleotide variants (SNVs), insertions/deletions (indels), and copy number alterations (CNAs) that might otherwise be missed.

Personalis’ ability to extract the maximum amount of usable data from each sample is also empowered by our unique sample-sparing protocols for all sample types.

Technical Details
Genes covered>20,000
Genes augmented (with ACE Technology)>8,000 biomedically-relevant genes, including >1,400 cancer-related genes
Sequencing informationConfiguration: ~120X
Read length: 2x150bp
Instrumentation: Illumina NovaSeq
Cancer analysis configurationPaired tumor/normal or tumor only
SpeciesHuman
ACE Research Transcriptome

The same accuracy and coverage enhancements of the ACE Research Exome (see above) are also incorporated into RNA analysis using our unique ACE Research Transcriptome enrichment protocol.

Many clinical studies depend on tissue archives that have been fixed using formalin-fixed, paraffin-embedded (FFPE) procedures. This preservation process makes it difficult to obtain a pure sample and often leads to RNA degradation and/or cross-linking. To overcome this challenge, Personalis has developed an exome-capture transcriptome protocol based on our ACE Technology that allows us to produce high-quality transcriptome sequencing results from challenging samples.

This capability is enabled by the use of multiple probes targeting each transcript, which facilitates the capture of transcripts even when the poly-A tail is lost due to RNA degradation; making it ideal for FFPE and other problematic sample types. This exome-capture RNA-Seq protocol ensures that >95% of the bases are mapped within the coding and untranslated regions (UTRs) of the RNA, contributing to enhanced fusion detection and gene expression analysis. This is also complemented by Personalis’ sample sparing protocols for all sample types, including more challenging types such as FFPE, fresh frozen, fine-needle aspirates (FNAs), and peripheral blood mononuclear cells (PBMCs).

Technical Details
Genes covered>20,000
Genes augmented (with ACE Technology)>8,000 biomedically-relevant genes, including >1,400 cancer-related genes
Sequencing informationConfiguration: 25-50M paired-end (50-100M total) reads
Read length: 2x150bp
Instrumentation: Illumina NovaSeq
Cancer analysis configurationTumor only
SpeciesHuman
Whole Transcriptome

While we promote the use of the ACE Research Transcriptome in the majority of RNA-Seq-related projects due to the benefits mentioned above, we also provide whole transcriptome services that utilize ribosomal RNA (rRNA)-depletion or poly-A-selection methodologies for the profiling of intact (non-degraded) RNA starting material, where applicable.

Technical Details
Genes covered>20,000
Sequencing informationConfiguration: 25-50 paired-end (50-100M total) reads
Read length: 2x150bp
Instrumentation: Illumina NovaSeq
Cancer analysis configurationTumor only
SpeciesHuman
Mouse

In recent years, the declining cost of NGS has resulted in the increased use of broad genomic characterization approaches, including whole genome sequencing (WGS), for various research applications. This cost reduction has coincided with researchers’ need for more comprehensive molecular information in the disease areas of cardiology, endocrinology, rare disease, autoimmunity, and ever-increasingly, cancer. WGS is an attractive option for many researchers due to its ability to provide insights into non-coding variation as well as it’s unrivaled resolution of genome-wide structural variation, the impact of which is becoming more pronounced in many disease states, especially cancer.

Personalis is one of the largest processors of human whole genome sequences in the world today and is your ideal partner for any WGS project across multiple disease areas.

Technical Details
Genes coveredAll coding and non-coding regions
Sequencing informationConfiguration: 30X or 60X (custom depths also available)
Read length: 2×150bp
Instrumentation: Illumina NovaSeq
Cancer analysis configurationPaired tumor/normal or tumor only
SpeciesHuman
ACE Extended Cancer Panel for DNA

The ACE Extended Cancer Panel covers a core set of >1,400 cancer-related genes, including clinically-actionable* genes as well as genes that have been identified in the literature as having a role to play in tumorigenesis. The panel provides deep and uniform coverage of genes associated with functional pathways that are known to be involved in cancer biology and it can be used to identify SNVs, indels, and CNAs in these genes. The panel’s accuracy has been enhanced with the utilization of our proprietary ACE Technology, which augments and repairs coverage gaps, especially in problematic regions such as those with high-GC content. This results in the characterization of genes with more complete coverage and greater variant detection performance than that of standard targeted NGS panels.

*Genes referred to here as being clinically-actionable reflects the fact that the efficacy of cancer drugs, FDA-approved or in clinical trials, are thought to be modulated by variants in these genes. This does not imply that this panel is for clinical use – it is for Research Use Only.

Technical Details
Genes covered>1,400
Sequencing informationConfiguration: >500X (tumor)/>100X (normal)
Read length: 2x150bp
Instrumentation: Illumina NovaSeq
Assay sensitivity>99%
Assay specificity (PPA)>99%
Cancer analysis configurationPaired tumor/normal or tumor only
SpeciesHuman

 

ACE Extended Cancer Panel for RNA

The ACE Extended Cancer Panel for RNA provides highly-accurate detection performance for variant types that are more difficult to identify with DNA sequencing analysis alone. The panel enables the identification of gene fusions, SNVs, and indels in the same >1,400 cancer-associated genes as the ACE Extended Cancer Panel for DNA, while also providing gene expression information for each of these genes. This assay enables the discovery of both clinically-actionable fusions involving critical genes such as ALK, ROS1, and RET, as well as novel fusions involving other targeted genes that might be missed by NGS panels that either target a smaller number of genes or that don’t provide RNA information.

As has been discussed in previous sections, Personalis’ targeted approach to RNA sequencing provides researchers with higher quality RNA results compared to those achieved by conventional practices. We accomplish this by focusing only on genes related to cancer biology (by excluding intronic RNA from unspliced transcripts) and by using a capture method that can isolate degraded RNA (which is particularly common in tumor FFPE samples) better than alternative methods. This results in higher quality RNA reads with minimized background.

Technical Details
Genes covered>1,400
Sequencing informationConfiguration: 5M paired-end (10M total)
reads; 2x150bp
Instrumentation: Illumina NovaSeq
Cancer analysis configurationTumor only
SpeciesHuman

Micro RNAs (miRNAs) are a small non-coding type of RNA molecule (18-40 nucleotides in length) that play a functional role in the regulation of RNA silencing and post-transcriptional gene expression. miRNA-Seq enables the investigation of the function of small RNAs and the evaluation of regulatory networks of miRNAs and their target genes.

Technical Details
Sequencing informationConfiguration: 10M single-end reads
Read length: 2x150bp
Instrumentation: Illumina NovaSeq
SpeciesHuman

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