Enabling Genomics Research:

How do Platform Technologies Fit withNext Generation Applications?

Jonathan Witonsky, Industry Manager

Drug Discovery Technologies

and Clinical DiagnosticsOctober 29, 2008

2

Focus Points

Background: Genomics Technologies and Applications

e.g. Gene Expression Analysis Applications

Markets: Growth Driven by Established and Emerging Trends

e.g. Nucleic Acid Purification and Isolation Markets

Supply-side Analysis: Product Positioning and Marketing

e.g. Next Generation Sequencing Technology

Demand-side Analysis: Usage of Genomics Technologies

e.g. Correspondence between Technologies and Applications

3

Background

Genomics Technologies and Applications

4

Background

Reagents

Instrumentation Software

Consumables

Technologies

Nucleic Acid Isolation

PCR

qRT-PCR

DNA Microarray

DNA SequencingTechnology

Applications

Gene Expression Epigenetics

Sequencing Genotyping Cytogenetics

5

Background (contd…)

Timeline of High-growth Periods for Genomics Applications

201420122010200820062004200220001998

de novo DNA sequencing /

resequencing for SNP discovery

gene expression analysis

genotyping

epigenetics / molecular cytogenetics (microarray)

201420122010200820062004200220001998

de novo DNA sequencing /

resequencing for SNP discovery

gene expression analysis

genotyping

epigenetics / molecular cytogenetics (microarray)

6

Background (contd…)

e.g. Gene Expression Analysis

Low density (moderate market growth)

Medium density (high market growth)

High density (moderate market growth)

Typical platform technology:

Real-time PCRTypical platform technology:

Standard DNA Microarray

Gene Expression Analysis

Sweet Spot for Novel Platform Technologies

7

Markets

Growth Driven by Established and Emerging Trends

8

Markets

20122012

20072007

20022002

Customer Priorities

Customer Priorities

Customer Priorities

1. Proof-of-principle

2. Basic research and discovery

1. Regulated in vitro diagnostics

2. Multiple commercialized

applications

3. Research workflows involve

multiple genomics technologies

4. Ultra-high throughput technologies

1. Validation

research

2. Clinical approval

3. Forensics and infectious disease

testing

20122012

20072007

20022002

Customer Priorities

Customer Priorities

Customer Priorities

1. Proof-of-principle

2. Basic research and discovery

1. Regulated in vitro diagnostics

2. Multiple commercialized

applications

3. Research workflows involve

multiple genomics technologies

4. Ultra-high throughput technologies

1. Validation

research

2. Clinical approval

3. Forensics and infectious disease

testing

9

Markets (contd…)

e.g. Nucleic Acid Purification and Isolation

Genomic DNA

27.8%

Plasmid DNA

27.1%

Fragment DNA

15.4%

RNA

29.7%

Percent of Revenues by Nucleic Acid Type (U.S.), 2007

Note: All figures are rounded; the base year is 2007. Source: Frost & Sullivan

12 – 14%Growth

0%Growth

5 – 7%

Growth

16 – 18%

Growth

10

Supply-side Analysis

Product Positioning and Marketing

11

Supply-side Analysis

Product Positioning #1

qPCR

DNA Microarray

CE Sequencing

Next GenerationSequencing

GeneExpression

SNPGenotyping

Epigenetics(DNA

Methylation,ChIP-chip)

Cytogenetics(CNP/CGH)

Epigenetics(DNA

Methylation,ChIP-chip)

Cytogenetics(CNP/CGH)

de novoSequencing

SNP Discoveryand

Resequencing

qPCR

DNA Microarray

CE Sequencing

Next GenerationSequencing

GeneExpression

SNPGenotyping

Epigenetics(DNA

Methylation,ChIP-chip)

Cytogenetics(CNP/CGH)

Epigenetics(DNA

Methylation,ChIP-chip)

Cytogenetics(CNP/CGH)

de novoSequencing

SNP Discoveryand

Resequencing

qPCR

DNA Microarray

CE Sequencing

Next GenerationSequencing

GeneExpression

SNPGenotyping

GeneExpression

SNPGenotyping

Epigenetics(DNA

Methylation,ChIP-chip)

Cytogenetics(CNP/CGH)

SNP Discoveryand

Resequencing

Nucleic AcidDetection/

QuantitationqPCR

DNA Microarray

CE Sequencing

Next GenerationSequencing

GeneExpression

SNPGenotyping

GeneExpression

SNPGenotyping

Epigenetics(DNA

Methylation,ChIP-chip)

Cytogenetics(CNP/CGH)

SNP Discoveryand

Resequencing

Nucleic AcidDetection/

Quantitation

Product Positioning #2

Product Positioning #3

Product Positioning #4

qPCR

DNA Microarray

CE Sequencing

Next GenerationSequencing

de novoSequencing

SNPGenotyping

Epigenetics(DNA

Methylation,ChIP-chip)

Cytogenetics(CNP/CGH)

GeneExpression

SNPGenotyping

SNP Discoveryand

Resequencing

de novoSequencing

SNP Discoveryand

Resequencing

Nucleic AcidDetection/

Quantitation

Nucleic AcidDetection/

Quantitation

qPCR

DNA Microarray

CE Sequencing

Next GenerationSequencing

de novoSequencing

SNPGenotyping

Epigenetics(DNA

Methylation,ChIP-chip)

Cytogenetics(CNP/CGH)

GeneExpression

SNPGenotyping

SNP Discoveryand

Resequencing

de novoSequencing

SNP Discoveryand

Resequencing

Nucleic AcidDetection/

Quantitation

Nucleic AcidDetection/

Quantitation

qPCR

DNA Microarray

CE Sequencing

Next GenerationSequencing

Epigenetics(DNA

Methylation,ChIP-chip)

Cytogenetics(CNP/CGH)

GeneExpression

SNPGenotyping

de novoSequencing

SNP Discoveryand

Resequencing

GeneExpression

SNPGenotyping

Epigenetics(DNA

Methylation,ChIP-chip)

Cytogenetics(CNP/CGH)

SNP Discoveryand

Resequencing

Nucleic AcidDetection/

QuantitationqPCR

DNA Microarray

CE Sequencing

Next GenerationSequencing

Epigenetics(DNA

Methylation,ChIP-chip)

Cytogenetics(CNP/CGH)

GeneExpression

SNPGenotyping

de novoSequencing

SNP Discoveryand

Resequencing

GeneExpression

SNPGenotyping

Epigenetics(DNA

Methylation,ChIP-chip)

Cytogenetics(CNP/CGH)

SNP Discoveryand

Resequencing

Nucleic AcidDetection/

Quantitation

12

Supply-side Analysis (contd…)

e.g. Next Generation Sequencing Technology

Genome Sequencer

FLX System(Roche Applied Science)

Genome Analyzer

System(Illumina, Inc.)

SOLiD™

Analyzer(Applied Biosystems)

• Ancient DNA• ChIP-seq/Methylation/

Epigenetics• Eukaryote Whole Genome• Expression Tags• HIV Sequencing• Metagenomics & Microbial

Diversity• Mitochondria/ Viruses/ Plastids/

Plasmids• Prokaryote Whole Genome• Sequence Capture Targeted

Region• Small RNA• Somatic Variation Detection• Transcriptome Sequencing

• De novo Sequencing• Whole-Genome Resequencing• Discovery of Somatic Genomic

Variation• Metagenomics• Epigenomics• Targeted Sequencing• Whole-Transcriptome Profiling• Protein-DNA or Protein-RNA

Interactions

• Targeted Resequencing• Gene Expression• MicroRNA Discovery• Whole Genome Sequencing

13

Demand-side Analysis

Usage of Genomics Technologies

14

Demand-side Analysis

Research Group 1 • Gene Expression /

Regulation• Gene Function

• Protein Expression

Research Group 2 • Cardiovascular

• Metabolic• Pre-clinical studies

Research Group 3• Developmental

Biology• Stem cells/ develop-

mental biology

• Service provider /

-central core facility

Research Group 5• Cancer Research /

Oncology• Drug Discovery /

Target Identification

Research Group 6• Evolutionary Biology

Research groups 4 and 6 tend

to not go together.

(negatively correlated)

Group 4 can

be pursued

separately or

together with

Group 2.

Research

Group 1 focus

can be pursued

in parallel with

all the other

areas.

Research Group 3 tends to be

pursued with Group 2.

Research Focus Area

Research Group 4• Infectious Disease/

Microbial detection & ID

• Immunology

Research Group 5

tends to be a

category in itself that

can, however, be

pursued in parallel

with other research

areas of focus.

15

Demand-side Analysis (contd…)

Application Group 1 • SNP Discovery / Resequencing

• Other mutation

screening

• Copy number

variation / loss of heterozygosity

studies

• Microsatellite

(STR) analysis

• Candidate gene genotyping

Application Group 2 • Histone

modification

profiling / ChIP-

chip

• Regulatory protein factor

binding studies

• DNA Methylation

State Profiling

• Small RNA/micro RNA expression

profiling

Application Group 3• Ribosomal sequencing

• Drug metabolism

pharmacogenic

profiling

• SAGE profiling / digital gene

expression

profiling

• Splice variant

expression profiling

Application Group 4• Clone identification

and verification

• CDNA

sequencing

• De novo sequencing

Application Group 5• Whole genome

gene expression

profiling

• Whole genome genotyping

studies

Application Group 6• Focused gene expression

profiling

• Novel or rare

transcript

expression profiling

Applications

Application

Group 6 focus

can be pursued

in parallel with

all the other

applications.

Research Group 3

tends to be a

category in itself that

can, however, be

pursued in parallel

with other

applications.

Group 4 can be

pursued

separately or in

parallel with the

other groups in

the other sub-

branch.

Research Group 5 tends to

be pursued with Group 1.

Group 2 can be

pursued separately

or together with

Group 1.

16

Demand-side Analysis (contd…)

Technology Group 1 • PCR/ Thermal Cycling

• DNA/RNA

isolation &

purification

technologies• qPCR/RT-PCR

Technology Group 3• Next generation sequencing

• Capillary

electrophoresis

sequencing

• Single molecule detection

platforms

Technology Group 6• Gel Based (Northern/

Southern /

Western)

Technology Group 5• Microarray• Robotics /

Automated

liquid handling

Technology Group 4• Multiplex Assay

Technology Group 2 • RNA interference

(RNAi/siRNA)

• Transfection

Group 1 can

be adopted

separately or

together with

Group 3.

Technology

Groups 5 and 6

can be pursued

in parallel with

all the other

areas.

Technology Group 4 tends

to be adopted with Group 3.

Technologies

Technology Group 2

tends to be a

category in itself that

can, however, be

adopted in parallel

with other

technologies.

17

Demand-side Analysis (contd…)

e.g. Drivers of Adoption: Next generation sequencing

Adoption of Next generation

sequencing

1.27

.76

Application Group 1 • SNP Discovery / Resequencing

• Other mutation screening• Copy number variation / loss of

heterozygosity studies

• Microsatellite (STR) analysis

• Candidate gene genotyping studies

Application Group 5• Whole genome gene expression

profiling

• Whole genome genotyping studies

Adoption of Next generation

sequencing

1.27

.76

Application Group 1 • SNP Discovery / Resequencing

• Other mutation screening• Copy number variation / loss of

heterozygosity studies

• Microsatellite (STR) analysis

• Candidate gene genotyping studies

Application Group 5• Whole genome gene expression

profiling

• Whole genome genotyping studies

18

Demand-side Analysis (contd…)

e.g. Drivers of Adoption: Microarray

Adoption of Microarray

.32

.71

.41

Application Group 6• Focused gene expression profiling

• Novel or rare transcript expression

profiling

Application Group 5• Whole genome gene expression

profiling

• Whole genome genotyping studies.52

Research Group 1 • Gene Expression / Regulation

• Gene Function• Protein Expression

Research Group 5• Cancer Research / Oncology

• Drug Discovery / Target

Identification Adoption of Microarray

.32

.71

.41

Application Group 6• Focused gene expression profiling

• Novel or rare transcript expression

profiling

Application Group 5• Whole genome gene expression

profiling

• Whole genome genotyping studies.52

Research Group 1 • Gene Expression / Regulation

• Gene Function• Protein Expression

Research Group 5• Cancer Research / Oncology

• Drug Discovery / Target

Identification

19

Demand-side Analysis (contd…)

e.g. Correspondence between Technologies and Applications

Whole genome

genotyping studies

Candidate gene genotyping studies

Whole genome gene expression profiling

Focused gene expression profiling

SAGE

profiling

Splice variant

expression profiling

Novel or rare transcript expression profiling

Small RNA/ micro RNA expression profiling

DNA methylation state profiling

Regulatory protein factor binding studies

Histone

modificationprofiling/

ChIP-chip

Copy number variation/ lossof heterozygosity studies

De novo sequencing

SNP discovery /

resequencing

Othermutation

rescreening

Clone identificationand verification

Microsatellite

(STR) analysis

DNA footprinting

CDNA Sequencing

Ribosomal

sequencing

Drug metabolismpharmacogenicprofiling genotyping

PCR/thermal

cycling

Gel Based

Multiplex

assay

qPCR/RT-PCR

Capillaryelectrophoresis

sequencing

Next

generationsequencing

Microarray

Robotics/ automated

liquid handling

Single molecule detection platforms

DNA/RNAisolation &

purification

technology

RNA interference

(RNAi/ siRNA )

Transfection

Whole genome

genotyping studies

Candidate gene genotyping studies

Whole genome gene expression profiling

Focused gene expression profiling

SAGE

profiling

Splice variant

expression profiling

Novel or rare transcript expression profiling

Small RNA/ micro RNA expression profiling

DNA methylation state profiling

Regulatory protein factor binding studies

Histone

modificationprofiling/

ChIP-chip

Copy number variation/ lossof heterozygosity studies

De novo sequencing

SNP discovery /

resequencing

Othermutation

rescreening

Clone identificationand verification

Microsatellite

(STR) analysis

DNA footprinting

CDNA Sequencing

Ribosomal

sequencing

Drug metabolismpharmacogenicprofiling genotyping

PCR/thermal

cycling

Gel Based

Multiplex

assay

qPCR/RT-PCR

Capillaryelectrophoresis

sequencing

Next

generationsequencing

Microarray

Robotics/ automated

liquid handling

Single molecule detection platforms

DNA/RNAisolation &

purification

technology

RNA interference

(RNAi/ siRNA )

Transfection

This chart shows the perceived correspondence between the

various technologies (red boxes) and applications (blue circles).

The selection applications closest to each technology are those

that are most closely associated with it and those that most

distinguish it from other technologies.

20

Demand-side Analysis (contd…)

Conclusions

• Majority of respondents are aware of most of the genomic technologies. Awareness is higher for PCR,

DNA/RNA isolation, qPCR and Gel-based. It is lowest for Single molecule detection platforms and Next

Gen sequencing.

• Most of the genomic technologies have been already adopted by majority of the respondents. Almost

universally adopted technologies include PCR, DNA/RNA isolation, qPCR, and Transfection.

• Technologies with the potential for a higher rate of adoption in the next 12 months include: Microarray,

RNA interference (RNAi/siRNA), Multiplex assay, Single molecule detection platforms, and Next generation

sequencing.

• A majority of the respondents are very satisfied with PCR and capillary electrophoresis sequencing.

• In hospitals/clinical labs more than 80% are very satisfied with robotics and 70% with gel-based

technologies.

• Satisfaction is lowest for microarray and RNA interference.

• The key reasons for satisfaction are: usefulness to research and ease of use.

• The key reasons for dissatisfaction with various technologies are: difficulty of use, high operating cost,

expensive or difficult sample preparation, and low accuracy.

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