andy felton ph.d. vice president product management · 2020. 7. 15. · ion s5/s5 xl system...
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State of the art of Ion Torrent technology Andy Felton Ph.D. Vice President Product Management
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Our Vision: Genetic Analysis
Next-generation sequencing for
genome, exome, or transcriptome sequencing
Next-generation sequencing for
targeted sequencing, and expression
analysis
Capillary electrophoresis for low-cost, targeted variant analysis
Real-time PCR systems for variant
ID, gene expression, and analysis of large numbers of samples
Digital PCR System for fast and simple rare allele detection and absolute target
quantification
Discover Analyze Characterize
To be the most relevant provider of high value information to
researchers and labs for genetic testing
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Our Impact: Ion Torrent™ NGS Systems
For Research Use only. Not for use in diagnostic procedures.
>1500 total publications
>100 peer-reviewed clinical oncology research publications
1000’s systems placed
>600 tests implemented in clinical research labs
Hundreds of thousands of test results generated
in clinical research labs
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Our View : Targeted Sequencing Cost efficient, time efficient and simpler to analyze
Number of variants
generated per run 10s to 100s ~50,000 ~3,000,000
Likely number of
relevant variants 1-10s 1-10s 1-10s
Time to analyze Hours to days Days to Weeks Weeks to Months
Total cost
Inc. analysis $ $$ $$$
Whole Genome Whole Exome Targeted Sequencing
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Developing the simplest targeted sequencing workflow
Hard to
Use
Easy to
Use
2010 2012 2014 2016
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The all new Ion S5™ and S5™ XL Systems.
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A single platform for many NGS application areas
Cancer Research
Reproductive Genomics Research
Inherited Disease Research
Infectious Disease Research
Gene panels for SNPs, indels, copy number, gene expression and
gene fusion detection
Gene panels and exomes for SNPs, indels and copy number
Aneuploidy detection Microbial whole genomes, microbial typing, metagenomics
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Applications Ion S5 and Ion S5 XL Systems
• Simplest NGS workflow for targeted sequencing - <15mins to set up a sequencing run and <45mins total hands-on time from DNA to data with Ion Chef™ System
• Fastest run time – 3.5 hours from sequence to BAM files.
• Lowest capital investment - Single platform for all targeted applications with flexibility to scale from 5M - 80M reads
• Lowest DNA/RNA input requirements – 1-10ng using Ion AmpliSeq™ technology
• Easy setup and training – single day installation and plug and play cartridge-based reagents
Simplest and fastest targeted sequencing system
with the lowest capital investment
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Ion 520™
5 M Reads
Ion 530™
15-20 M Reads
Ion 540™
60-80 M Reads
• Gene panels to exomes and
transcriptomes on a single low cost
platform
• Built-in Informatics - no external server
required
• Upgradable from S5 to S5 XL
configuration
Ion S5 System
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Ion S5 XL System
• Rapid sequencing and analysis for
labs requiring more output or multiple
runs per day
• The computing power to enable rapid
turnaround times from any size of
experiment
• 1 hr analysis time for gene panels,
5 hr analysis for transcriptomes
Ion 520™
5 M Reads
Ion 530™
15-20 M Reads
Ion 540™
60-80 M Reads
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Ion S5/S5 XL System Performance
200bp
Sequencing
Time
S5/S5 XL
200bp
Analysis
Time*
S5 XL
200bp
Analysis
Time*
S5
Output Reads Read Length
• Analysis time to BAM file
Ion 530™ Chip 2.5 hr ~2.5 hr ~8 hr 3-5 Gb 15-20 M Up to 400bp
Ion 540™ Chip 2.5 hr ~5 hr ~16.5 hr 10-15 Gb 60-80 M Up to 200bp
Ion 520™ Chip 2.5 hr ~1 hr ~5 hr 1-2 Gb 3-5 M Up to 400bp
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Ion S5 XL – Time to result and capacity for multiple runs per day
10 10 5
40 40
20
0
10
20
30
40
50
520 530 540
Maximum Runs Per Week* 24 hour workday
Ion S5 Ion S5 XL
* 200bp runs, 24 hours/day, 5 days/week
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Temp Controlled Chip Clamp
Wash Solution
&
Waste Cartridge (behind W2 Solution)
Sequencing Reagent
Cartridge
Large HD Touchscreen
Automated
Cleaning Solution
Standard Power
Gas
Water
Plug and Play Reagents
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Single Use Consumables & Easy Tracking with RFID tags
RFID
tag Tracking
Electronic
Barcode
(1x use)
Reagent
Cartridge
(1x use)
Wash
Solution
(1x use)
Waste
Container
(Reusable)
Cleaning
Solution
(4x use)
Universal kit for any chip type or read length 12 month Shelf-Life
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Infectious
Disease
Panels
Gene
Fusions Txome
&
RNA
Expression
Oncology
Panels Inherited
Disease
Panels &
Exomes
Ion AmpliSeq™ Technology – A single workflow for many applications
Copy
Number
Variants
Ion AmpliSeq™ technology
Amplify Digest Ligate
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Ion Chef™ System & Ion AmpliSeq technology From DNA to library with 15 mins of hands-on-time & 2 pipetting steps per sample
Amplify Digest Ligate Equalize Combine
Ion Chef & Ion AmpliSeq™ technology
• 8 Ion AmpliSeq™ libraries per run
• Compatible with all 1 or 2 primer pool AmpliSeq panels
• DNA or cDNA input
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Ion Chef for Library & Templating with Ion S5 Systems Up to 40 Libraries Per Week
Workflow Unit Day Night Day Night Day Night Day Night Day Totals
Library Prep Samples 8 8 8 8 8 40
Templating Samples 16 16 8 40
Sequencing Chip 2 2 1 5
Mon Tue Wed Thu Fri
Assumes an 8 hour work day, 5 day work week
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Ion AmpliSeq™ Designer Ion Reporter™ Software Torrent Suite Software
Build & order Ion AmpliSeq™
panels focused on your genes
and organisms of interest
Perform basecalling
and alignment for
single samples
Identify and annotate your
variants of interest with
public or private databases
& perform multi-sample
comparison
Design, interpret and confirm your results with Ion Torrent Software Solutions
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Ion S5 System Performance
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Internal data shows reliable output from 3M to 80M reads
Number of runs 19 12 32
Mean Read Length 348 bp 326 bp 188 bp
Raw Read Accuracy 99.1% 99.2% 98.4%
0
2
4
6
8
10
12
14
16
0
10
20
30
40
50
60
70
80
90
100
520 530 540
Gig
ab
ase
s
Re
ad
s/ M
total reads total bases
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Excellent variant calling performance with Ion AmpliSeq Exome
98.4% 97.8%
98.4%
80.0%
82.0%
84.0%
86.0%
88.0%
90.0%
92.0%
94.0%
96.0%
98.0%
100.0%
SNV Sensitivity(%) CombinedSensitivity(%)
Combined Precision(%)
Ion 540 Chip Variant Call Performance
n=32 n=32 n=32
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Early Access Data From Multiple Sites & Multiple Runs
0
5,000,000
10,000,000
15,000,000
20,000,000
25,000,000
30,000,000
Ion 530 Chip Avg Total Reads
Site 1
Site 2
Site 3
Site 3
Site 4
Site 5
0
20,000,000
40,000,000
60,000,000
80,000,000
100,000,000
Ion 540 Chip Avg Total Reads
Site 1
Site 2
Site 3
Site 4
98.6% 98.6%
98.4% 98.4%
90%
92%
94%
96%
98%
100%
Ion 540 Avg Raw Read Accuracy
Site 1
Site 2
Site 3
Site 4
99.4% 99.1%
99.3%
99.3% 99.3% 99.7%
90%
92%
94%
96%
98%
100%
Ion 530 Chip Avg Raw Read Accuracy
Site 1
Site 2
Site 3
Site 4
Site 5
Site 6
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Ion 530™ Chip offers >3X more reads vs. Ion 318™ Chip with equivalent performance
5
249
99.7
23
251
99.4
19.6
250
99.4
0
50
100
150
200
250
300
Total # Reads Q20 Mean RL Raw Read Accuracy (%)
Hi-Q Validation Data Ion 318™
Genomic Health Ion 530™
Uppsala Univ Ion 530™
Ion 318 internal data
Test Site #1
Test Site #2
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Download datasets at Ion Community
520: https://ioncommunity.thermofisher.com/docs/DOC-9687
530: https://ioncommunity.thermofisher.com/docs/DOC-9688
540: https://ioncommunity.thermofisher.com/docs/DOC-9689
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New Products for Key Application Areas
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Ion AmpliSeq™ Mendelian Disease Research Panels Content Summary
*For Research Use Only. Not for use in diagnostic procedures.
13 panels grouped by disease
research area
Average Gene Coverage
Reads on Target
Positive Predictive Value
True Positive Rate
A Comprehensive Array of Gene Panels for Research
Targeting Rare Inherited Diseases.
>3000 genes
99%
95%
99%
94%
Extensive curation of gene content and
amplicon design
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Disease Research Areas and Number of Genes
Renal, 96 Deafness, 124
Pulmonary, 130
GI, 189
Derm, 214
Primary Immune Deficiency, 264
Endocrine, 310
Vision, 330
Dysmorph-Dysplasia, 389
Heme, 404
Cardiovascular, 410
Inborn Errors of Metabolism, 569
Neurological, 766
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Great performance on Ion S5 Systems Ion AmpliSeq™ Inherited Research Panels (13 panels)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Coverage Uniformity Reads on target
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Ion AmpliSeq™ Pharmacogenomics Panel Content Summary
*For Research Use Only. Not for use in diagnostic procedures.
Fully automated workflows
Genes
Relevant variants
CYP2D6 Gene CNV
CYP2D6 Exon 9 CNV
Targeting relevant variants across genes associated with drug
metabolism enzymes and published evidence
40 genes
40
137
1
1
Genotyping and CNV in a single assay
33 The content provided herein may relate to products that have not been officially released and is subject to change without notice
Variant Call Performance Ion AmpliSeq™ Pharmacogenomics Panel
99
99.2
99.4
99.6
99.8
100
Cell Line Buccal Swab
% G
enoty
pe A
ccura
cy
Genotype Accuracy
0
20
40
60
80
100
120
140
0 1 2 3N
um
be
r o
f S
am
ple
s
Copy Number CYP2D6 gene
False Positive
No Call
True Positive
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Oncomine Comprehensive Assay* Content Summary
*For Research Use Only. Not for use in diagnostic procedures.
Categorized by somatic alteration type
Hotspot genes
Focal CNV gains
Full CDS for DEL
mutations & CNV loss
Fusion drivers
143 genes: Several used in multiple applications
(hotspot, CNV, driver fusion)
143 genes
73
49
26
22
Categorized by potential relevance
12
9
72
>450(US)
Labels
Guidelines
Drug Targets
Clinical Trials
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Panel Performance for Ion 530 Chip with Oncomine Comprehensive Panel
Avera
ge %
0
10
20
30
40
50
60
70
80
90
100
Ion 318 (1) Ion 530 (3) Ion 540 (14)
Base Uniformity Amplicon Uniformity
Chip (# samples)
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Variant Call Performance Ion 530 Chip
97.3%
92.7%
98.4%
100.0%
80%
82%
84%
86%
88%
90%
92%
94%
96%
98%
100%
SNP sensitivity Combinedsensitivity
Combined PPV CNV detection
Samples • 80:20 mix AcroMetrix™ Oncology Hotspot Control (DNA): three lung cancer cell line (RNA)
• 80:20 mix CRL-1619 cell line (DNA): three lung cancer cell line (RNA)
• 80:20 mix HCC1143D (known CNV) cell line (DNA): normal colon cell line (RNA)
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Ion AmpliSeq TB Research Panel Content Summary
*For Research Use Only. Not for use in diagnostic procedures.
Tested on six wild type (H37Rv) and six
rifampicin `resistant (mutation in rpoB) strains
on 520 chip
Amplicons
Genes
Samples per 520 Chip
False positives
Panel targeting key Mycobacterium tuberculosis genes associated
with antibiotic resistance
8 genes
109
8
6
0
Ion AmpliSeq Microbial Design Capability Single organisms or multi-target panels
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Ion AmpliSeq, Ion Chef and Ion S5 Systems.
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Thank you
For Research Use Only. Not for use in diagnostic procedures. © 2015 Thermo Fisher Scientific Inc. All rights reserved. All trademarks are the property of Thermo Fisher Scientific and its subsidiaries unless otherwise specified.
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