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www.personalis.com | info@personalis.com | +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
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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.
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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
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5Pioneering Genome-Guided Medicine
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).
* Available for ACE Exome only
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7Pioneering Genome-Guided Medicine
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
* Available for ACE Exome only
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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 | info@personalis.com
SALES CONTACTUnited States: info@personalis.comEurope: europe@personalis.comOther Countries: info@personalis.com
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
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