ACE Cancer Research Services - Personalis · 2020. 11. 7. · total of 16 Gigabases (G) of sequencing. The ACE Cancer Research Exome covered greater than 99% of bases at ≥20X average

www.personalis.com | [email protected] | +1 855-GENOME4 (436-6634) | +1 650-752-1300

The most comprehensive tumor profiling and informatics services for research and clinical trials

ACE Cancer Research Services

Personalis, Inc.1330 O’Brien DriveMenlo Park CA 94025USA

September 2015

BRH_ACE_Cancer_Services_1.3.indd 1 8/26/15 12:37 PM

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Tumor Analysis for Cancer Research and Clinical Trialswith Accuracy and Content Enhanced (ACE) Technology

Personalis, Inc. ACE Services for Cancer

The Personalis expanded portfolio of cancer research solutions is the most comprehensive and accurate genomics and informatics service for

tumor profiling. Based on the ACE Platform®, our end-to-end cancer research services combine DNA and RNA analysis to provide a comprehensive

tumor genomic profile from a single sample.

ACE Extended Cancer Panel for DNA Analysis With >1,300 cancer genes and >200 miRNA genes, the panel provides more

coverage of gene pathways and functions known to be involved in cancer biology than any other commercially available panel

ACE Extended Cancer Panel for RNA Analysis Analyze RNA from the same sample to detect variant types not detected by

DNA analysis alone, with deep coverage of cancer-related transcripts

ACE Exome for Cancer Research Accuracy and Content Enhanced Whole Exome and Analysis, with

~8,000 biomedical genes enhanced, including enhanced coverage of >1,300 cancer genes (ideal for discovery research)

Whole Transcriptome for Cancer Research Perform RNA analysis on the same sample with high depth whole

transcriptome analysis to identify novel gene fusion events

Broad Services for Cancer Research

Support a wide variety of sequencing methodologies, including targeted high-depth sequencing, exome sequencing and RNA-Seq

Enhance DNA sequencing coverage using ACE Technology

Accept a variety of sample types, including Formalin-Fixed-Paraffin-Embedded (FFPE) samples and Fine Needle Aspirates (FNAs)

Perform paired tumor/normal and tumor-only analyses

Provide broad analysis including somatic small variant and indel calling, CNV analysis, fusion junction calling, and gene expression profiling, as well as germline small variant calling and annotation

Enhance interpretation by providing detailed annotation, including structural and functional information from over 40 public and proprietary databases including COSMIC, Cancer Gene Census, and The Cancer Genome Atlas

For Cancer Research Studies, We...

Sample TypesFor tumor/normal projects, many studies utilize tissue archives that have been fixed using FFPE procedures. FFPE induces protein–protein and protein–nucleic acid crosslinking, making it difficult to separate DNA from histones and to obtain a pure sample. This process can also lead to DNA fragmentation. Personalis scientists have optimized extraction methodologies for challenging cancer samples to achieve successful results. In addition to FFPE sample we also accept fresh frozen tissue, blood, FNAs, DNA, and RNA samples.


3Pioneering Genome-Guided Medicine

ACE PlatformAugmented Sequencing Methods for Improved Coverage and Accuracy

Cancer Research Studies

The Personalis mission is to provide the most accurate next-generation sequencing and interpretation services. To enable this, we have

developed the Accuracy and Content Enhanced (ACE) Platform to provide high accuracy sequencing, informatics and content.

Sample Prep and Sequencing

Variant Annotation

Analysis and Interpretation

Better Accuracy and Coverage

More Accurate Variant Detection

More Accurate and Comprehensive Annotation

Better Discovery

Research Services Clinical Services Cancer Services

Alignment and Variant Discovery

Improves coverage of biomedically important

regions including difficult to sequence

regions such as those with high GC

Provides best-in-class

alignment, enhanced reference, and variant calling for improved

accuracy

Curated proprietary databases, integrated

with over 40 additional public and commercial

databases

Comprehensive analysis and

interpretation

Higher Accuracy Enables Improved Discovery

ACE Platform


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ACE Exome Sequencing for Cancer Research

Personalis, Inc. ACE Exome Sequencing for Cancer Research

Personalis provides a wide range of sequencing

capabilities that are significantly enhanced with our

proprietary ACE technology. ACE provides targeted

sequencing to augment coverage gaps present

in typical panels and exomes, including enhanced

coverage for over 1,300 cancer genes. Improved

coverage with ACE translates into increased sensitivity

to detect known and novel cancer-associated variation

as part of a discovery study, and improved resolution in

studies of tumor stratification, metastatic evolution and

therapeutic response.

Whole Transcriptome for Cancer ResearchTranscriptome sequencing can provide complementarity information to your cancer studies, including data on gene expression levels, fusion transcripts, variants in expressed genes and allelic expression. RNA can be extracted from the same tissue sample used for exome sequencing, maximizing the data generated from limited samples.

FIGURE 1: Example exon coverage for cancer genes using the ACE Exome vs. standard exome sequencing.

ACE vs. Standard Coverage

ACE Exome 16GExome A 16GExome B 16GExome C 16GExome D 16G

909999.9200

400

600

800

1000

1200

1400

1600

Multi-assay Finishing of 1,600 Cancer Genes

Percent of Coding Bases with Coverage ≥20x, Sample Average

Num

ber

of G

enes

We investigated completeness of coverage over a list of 1,600 genes known to be involved in cancer biology (including the Cancer Gene Consensus list) by comparing the ACE Cancer Research Exome with current standard exome offerings from major commercial vendors. The ACE Cancer Research Exome and each standard exomes were run to a total of 16 Gigabases (G) of sequencing. The ACE Cancer Research Exome covered greater than 99% of bases at ≥20X average (mean) depth on 1,470 (92%) of the genes. Standard exomes only covered 1,314 (82%), 1,093 (68%), 897 (56%) and 1080 (68%), respectively.

FIGURE 2: Overall performance of ACE Cancer research Exome vs. standard exomes at 16G sequencing on 1,600 cancer genes.

Content Position

MAP2K1

with ACE Exome™ CoverageStandard Exome

TP53

NF1

BRAF



Pathways Panel 1 Panel 2 Panel 3ACE Extended Cancer Panel

Difference ≥

Notch 5 9 8 15 67%

P13K-Akt 67 67 103 125 21%

P53 18 19 24 31 30%

TGF-beta 11 12 20 30 50%

MAPK 37 46 58 90 55%

JAK-STAT 26 33 36 52 45%

Apoptosis 17 18 22 37 68%

Cell cycle 28 31 42 55 31%

Transcriptional misregulation

30 35 48 99 106%

miRNA 51 53 69 185 168%

ACE Extended Cancer Panel for DNA and RNA Analysis

ACE Extended Cancer Panel for DNA and RNA Analysis

* 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 a Research Use Only service.

TABLE 1: Example of the number of genes included in commercially available panels.

The accuracy of our ACE Cancer Panel has also been enhanced over standard NGS panel approaches by augmenting and repairing coverage gaps, especially in targeted regions with high-GC content. This is accomplished by performing separate targeted capture under optimized sample prep conditions and combining data from these separate targeted preps into a single high quality sequencing dataset. This results in genes with more complete coverage.

ACE Extended Cancer Panel for DNA Analysis

The most advanced of its kind, the ACE Extended Cancer Panel includes a core set of clinically actionable* genes, all genes in the Cancer Gene Census, genes from TCGA reports, those within canonical cancer pathways proposed by Vogelstein et al., (Science, Mar 29 2013) and other leading academic groups, as well as an additional 200 cancer related microRNA genes and important pharmacogenomic genes*.

The ACE Extended Cancer Panel has been designed to support both discovery research and clinical trials. It provides more coverage of gene pathways and functions known to be involved in cancer biology than any other panel commercially available. (TABLE 1). Until now discovery researchers have had to make a choice between the breadth of sequencing used to find novel variants in cancer-related genes and the depth of sequencing needed to identify variants present at low allelic fraction. The Personalis Extended Cancer Panel is the first service to combine the breadth of coverage for novel variant discovery across key cancer pathway genes and the sequencing depth needed to detect variants present at low allelic fraction.

The Personalis ACE Extended Cancer Panel is a comprehensive and augmented panel for cancer research and clinical trials. Covering more than

1,300 cancer genes, the Extended Panel is the most complete and accurate solution for tumor profiling.

>1,300 cancer genes plus >200 miRNA genes

Augmented for accuracy with ACE technology

Comprehensive coverage of key cancer pathway genes

>500x mean coverage over the extended footprint (DNA)

Sensitivity for both known and novel fusion events (RNA)

Complete informatics analysis

• Alterations reported include SNVs, CNVs, gene fusions and low-level variant expression

• Most accurate and extensive variant annotation with >40 public and proprietary databases including COSMIC, The Cancer Genome Atlas, and Cancer Gene Census


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Personalis, Inc. ACE Cancer Analysis and Annotation Pipeline

DNAExtraction

LibraryPrep

DNASequencing

TumorSample

Tumor Sample Analysis

PersonalisDNA Analysis

Pipeline

VariantCalls

AlignedReads

VariantAnnotations

DNAExtraction

LibraryPrep

DNASequencing

NormalSample

Normal Sample Analysis

PersonalisDNA Analysis

Pipeline

AlignedReads

VariantCalls

VariantAnnotations

Somatic Analysis

PersonalisSomatic

QC ReportEngine

SomaticVariantCalling

SomaticCNV

Calling

PersonalisCancer

AnnotationEngine

Data Deliverables

Raw Reads[Tumor & Normal

Samples]

Aligned Reads[Tumor & Normal

Samples]

Variant Calls[Tumor & Normal

Samples]

Variant Annotations[Tumor & Normal

Samples]

QC Report[Tumor & Normal

Samples]

SomaticVariant Calls

SomaticQC Report

Somatic Variant Annotations• All Variants• Cancer Relevant Variants• Low-frequency Somatic Variants

Somatic CNV Annotations• Somatic LOH Report*• Somatic CNV Report

* Available for ACE Exome only

ACE Extended Cancer Panel for RNA AnalysisThe Personalis ACE Extended Cancer Panel for RNA analysis allows for an unparalleled detection of unique variant types not identifiable by DNA sequencing analysis alone. Our panel is the first of its kind and targets the coding RNA of the >1,300 cancer panel genes, providing detection of important cancer associated features. For example, due to the breadth of our ACE Cancer Panel RNA sequencing, we are able to identify SNVs, Indels, gene expression levels, and gene fusion events in a very wide array of cancer-associated genes. Personalis’ ACE Extended Cancer Panel for RNA allows for extensive gene fusion discovery of both clinically actionable* fusions involving critical genes such as ALK, ROS1 and RET and novel fusions involving other targeted genes that might otherwise be missed.

The Personalis targeted approach to RNA sequencing benefits researchers in two ways, when compared with conventional (untargeted) RNAseq. First, it focuses sequencing on the genes actually involved in cancer biology, allowing deeper sequencing coverage of this RNA. Secondly, it largely excludes intronic RNA from unspliced transcripts. This eliminates a major source of background, again allowing deeper interrogation of the actual mRNA. For FFPE samples where the RNA may be degraded, targeted RNA sequencing has a third benefit : it can capture the RNA of exons distal to the poly-A tail, even if few transcript molecules remain intact connecting the two.

NOTE: Fusions 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 occurrence of these fusions. This does not imply that this panel is for clinical use – It is a Research Use Only service

ACE Cancer Analysis and Annotation Pipeline

DNA Analysis

The Personalis DNA Analysis Pipeline for Cancer performs high accuracy alignment and variant calling for both germline and somatic variants. Somatic variants can be identified in either Tumor/Normal, or from Tumor-only data sets. Somatic variant types including single nucleotide variants (SNVs), small insertions and deletions (indels), and copy number variants (CNVs) are reported. Loss of heterozygosity is also reported*. All of these variants are annotated against databases of known variants and cancer information and collated into reports. In addition, filtered and refined reports are generated for ease of use. Finally, QC reports delineating sequencing metrics as well as somatic analysis summary statistics are included in html format (TABLE 2).




ACE Services for Cancer

RNAExtraction

LibraryPrep

RNASequencing

TumorSample

RNA Tumor Sample Analysis

PersonalisRNA, QC Report

Engine

Data Deliverables

Variant Calls

Fusion List

RAW and AlignedReads

Variant Annotations

Cancer-specificVariant Calls

Gene ExpressionRead Counts

Cancer-specificVariant Annotations

RNA Summary Report• Fusion Junction Report• Variant QC Stats• Read QC Stats

• Cancer Variant Stats• Gene-based Expression Report

GeneExpressionDetection

RNA VariantCalling

unfiltered, filtered,& strictly filtered

FusionDetection

RNAAlignment

GeneExpression

Read Counts

FusionList

PersonalisCancer

AnnotationEngine TABLE 2: Data Analysis Deliverables

RNA Analysis

The Personalis RNA Analysis Pipeline for Cancer performs a high accuracy gapped alignment and variant calling. Personalis’ pipeline is capable of detecting a wide variety of important cancer related events from RNA sequencing data, including SNVs, Indels, and gene fusion events. Comparison of variants identified in RNA vs DNA, from the same sample, makes it clear which DNA variants are actually expressed, and at what level, in the tumor. RNA read depths can also be used to digitally quantify relative gene expression. To further empower researchers, our pipeline thoroughly annotates variants using a wide variety of sources, including information covering many important cancer features. As with the DNA analysis, detailed reports are provided for each variant class, easing accessibility (TABLE 2).

Comprehensive Annotation

We have created a comprehensive annotation engine that utilizes industry standard cancer databases (e.g., COSMIC, Cancer Gene Census, HGMD, etc.), pathway databases, drug-gene interaction databases (e.g., Drugbank), and hand-curated cancer gene annotations from the literature to generate annotated cancer variant reports for both somatic and germline variants.

Research Use OnlyThe Personalis genetic testing services for cancer applications are being initially offered for research use only. They have not yet been CLIA validated, and they have not been submitted for review by the US FDA or any other regulatory agency.

Cancer DNA Analysis Cancer RNA Analysis

Raw Data Files: FASTQ, BAM files Raw Data File: FASTQ, BAM files

Somatic Variant Calls: VCF files Variant Calls: VCF files

Somatic Variant Annotated Reports: VAR files• Cancer-relevant variant subsets and

annotations

Cancer-associated Filtered Variant Calls: VCF files

Annotated Copy Number Reports Cancer-associated Filtered Annotation Reports

Copy Number Plots Fusion Junction Reports

Somatic LOH Plots* Gene-based Expression Report

Sequencing and Alignment QC Reports Alignment QC Report

Somatic QC Report Variant QC Report



ACE Services for Cancer

Improving the Accuracy and Quality ofTumor Sequencing and Analysis

© 2015 Personalis, Inc. All rights reserved. Personalis®, ACE Platform®, ACE Exome®, ACE Clinical Exome®, and ACE Genome® are registered trademarks or trademarks of Personalis, Inc., (“Personalis”) in the United States and/or other countries.

Personalis, Inc.1330 O’Brien DriveMenlo Park, CA 94025

+1 855-GENOME4 (436-6634) | +1 650-752-1300www.personalis.com | [email protected]

SALES CONTACTUnited States: [email protected]: [email protected] Countries: [email protected]

LEARN MORETo learn more about the ACE Services for Cancer, please visit www.personalis.com/cancer or contact your local Personalis representative.

100-647-A SEPTEMBER 2015


Documents

ACE Cancer Research Services - Personalis · 2020. 11. 7. · total of 16 Gigabases (G) of sequencing. The ACE Cancer Research Exome covered greater than 99% of bases at ≥20X average