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



https://ioncommunity.thermofisher.com/docs/DOC-9687









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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


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


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

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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


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.

andy felton ph.d. vice president product management · 2020. 7. 15. · ion s5/s5 xl system...

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