Next-Generation
June 2009
Sequencing:
Solving the Genome
Ken Rubenstein, PhD
Next-generation sequencing (NGS) technologies are
advancing in quality and applications diversity at a
breathtaking pace. The market is diversifying strongly into
labs without previous involvement in sequencing. This
report examines:
• Current NGS platforms and how they compare
• Market dynamics and competitive landscape for
new entrants
• Next-generation systems in development
• Bioinformatics issues
• Applications of NGS
• User survey results and views of
interviewees
Continued on next page
Exploring the
depths of the
human
genome
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Overview
The first generation of DNA sequencing can be said to have
ended when the first few human genomes were sequenced
and a large number of genetic variations were detected in
a relatively few individuals. Sequencing throughput is rising
dramatically as costs per unit of sequence are falling equally
dramatically. Now it has become possible to sequence a sufficiently
large number of human genomes to explore the extent
and medical meaning of genetic variations in statistically
meaningful ways. The race to the “$1,000 genome” is well
underway, and the number of entrants is surprisingly large, as
are the ingenuity and inventiveness that have been brought
to race.
Next-Generation Sequencing: Solving the Genome provides
a detailed overview of the technologies involved in
next-generation sequencing, starting with the four systems
currently on the market and continuing with those now in
Source: Insight Pharma Reports
development. A number of companies have technologies that
promise some advantage over existing systems, but whether
those advantages will be great enough to merit significant
market share remains an open question. We also provide
an overview of bioinformatics issues in next-generation sequencing
and a comparative analysis of currently available
platforms.
Applications of next-generation sequencing discussed in this
report include whole-genome sequencing, RNA resequencing,
ChIP-seq, disease prediction and diagnosis, and personal
genomics. Next-generation sequencing is starting to impinge
on DNA microarray usage and should continue to do so as
costs drop. Existing next-generation sequencing users are
striving to expand the case for personal genomics and for
personalized medicine in general. Next-generation systems
are currently enabling the genome-wide association studies
needed to identify the genome variants central to deeper understanding
of the molecular basis of genetically complex diseases
and predicting individual risk of developing them.
Next-Generation Sequencing: Solving the Genome examines
market dynamics and includes discussions of key issues
relating to the competitive position of various technologies
and companies. Next-generation sequencing instruments
and consumables are selling rapidly and contributing nicely
to growth rates of the market leaders. Second-round players
must offer significant improvements over current market
entrants in order to merit viable market share. Third-round
technologies, particularly those involving nanopores, remain
speculative at present, but could serve to accelerate market
decentralization by virtue of extremely low costs and high
speeds.
About the Author: Ken Rubenstein, PhD, a biochemist and molecular biologist, received his PhD at the University of Wisconsin
and postdoctoral training at the University of Pennsylvania School of Medicine. He was a key innovator and research manager
for Syva Company, the diagnostics branch of Syntex Corporation. During his 13 years with Syva, Dr. Rubenstein became
vice president, scientific affairs, a function that included strategic planning. Since 1983, he has served as a technology and
marketing consultant to biomedical companies and an industry analyst, with more than 40 published studies to his credit.
Tables and Figures
Figures
Sanger Sequencing Methodology
Roche/454 Sequencing Concept
The Illumina Genome Analyzer Sequencing Concept
The Applied Biosystems SOLiD Sequencing Concept
The Complete Genomics cPAL Sequencing Concept
The Pacific Bioscience Sequencing Concept
Tables
Relative Performance of Applied Biosystems, Illumina, and 454
Sequencers
Comparison of Applied Biosystems, Illumina, and 454 Sequencers
with Sanger Sequencing
Selected Deals in the Next-Generation Sequencing Space
SURVEY EXHIBITS
Chief Application of DNA Sequencing, Industry Respondents
Chief Application of DNA Sequencing, Academic Respondents
Main Organism for Next-Generation Sequencing, Industry Sector
Main Organism for Next-Generation Sequencing, Academic Sector
User Experience with Next-Generation Platform, Industry Sector
User Experience with Next-Generation Platform, Academic Sector
Next-Generation Platform Predicted to Dominate in 2–3 Years, Industry
Sector
Next-Generation Platform Predicted to Dominate in 2–3 Years,
Academic Sector
Most Exciting Third-Generation Platform, Industry Sector
Most Exciting Third-Generation Platform, Academic Sector
Applications to Benefit Most from Next-Generation Sequencing,
Industry Sector
Applications to Benefit Most from Next-Generation Sequencing,
Academic Sector
To order a report, e-mail rlaraia@healthtech.com, call Rose LaRaia at 781-972-5444, or order on-line
Tables and Figures (cont.)
Research Areas to Benefit Most from Next-Generation Sequencing,
Industry Sector
Research Areas to Benefit Most from Next-Generation Sequencing,
Academic Sector
Biggest Technical Concern about Next-Generation Sequencing
Platforms, Industry Sector
Biggest Technical Concern about Next-Generation Sequencing
Platforms, Academic Sector
Biggest Computational/IT Concern, Industry Sector
Biggest Computational/IT Concern, Academic Sector
Adequate Cost/Benefit from Next-Generation Sequencing, Industry
Sector
Adequate Cost/Benefit from Next-Generation Sequencing, Academic
Sector
Cost of Full Human Genome Sequence by 2010, Industry Sector
Cost of Full Human Genome Sequence by 2010, Academic Sector
Opinion on Platform Market Dominance, Industry Sector
Opinion on Platform Market Dominance, Academic Sector
Does Sanger Sequencing (Capillary) Play a Role after 2010, Industry
Sector?
Does Sanger Sequencing (Capillary) Play a Role after 2010, Academic
Sector?
Most Important Factors in Selecting a Next-Generation System,
Industry Sector
Most Important Factors in Selecting a Next-Generation System,
Academic Sector
Buy Sequence from a 3rd-Party Service Provider, Industry Sector?
Buy Sequence from a 3rd-Party Service Provider, Academic Sector?
Table of Contents
Chapter 1: INTRODUCTION
1.1. Background
1.2. Scope and Nature of the Report
Chapter 2: HISTORY AND EVOLUTION OF SEQUENCING
TECHNOLOGY
2.1. Frederick Sanger & Early DNA Sequencing
2.2. Leroy Hood Pioneers Semi-Automated Sequencing
2.3. The Human Genome Project and
Celera Genomics: Race On
2.4. The $1,000 Genome & Next-Generation Systems
Chapter 3: SEQUENCING TECHNOLOGIES:
NEXT-GENERATION AND BEYOND
3.1. Current Next-Generation Sequencers
Roche/454 Life Sciences
Illumina
Applied Biosystems
Helicos
3.2. Sequencers Currently in Development
Complete Genomics
BioNanomatrix
VisiGen
Pacific Biosciences
Dover Systems
Intelligent Bio-Systems
ZS Genetics
Reveo
LightSpeed Genomics
3.3. Nanopore-Based Systems
NABsys
Oxford Nanopore Technologies
3.4. Performance Comparisons
3.5. Bioinformatics
3.6. Sample Preparation
3.7. National Human Genome Research Institute (NHGRI)
Funding
3.8. Intellectual Property Issues
Chapter 4: APPLICATIONS OF NEXT-GENERATION
SEQUENCING TECHNOLOGIES
4.1. Whole-Genome Sequencing
The 1,000 Genomes Project
Exon Sequencing
Accuracy and Precision in Genetic Variation Studies
4.2. RNA Sequencing
4.3. Gene Regulation and Control Analysis
4.4. Disease Diagnosis and Prediction
Cancer Genomics
Personal Genomics
4.5. Metagenomics
Chapter 5: MARKET DYNAMICS
5.1. Deals
5.2. User Survey Results
Chief Application for Next-Generation DNA Sequencing
Main Organism for Next-Generation Sequencing
User Experience with Next-Generation Platform, Industry Segment
Next-Generation Platform Predicted to Dominate in 2–3 Years
Most Exciting Third-Generation Platform
Applications to Benefit Most from Next-Generation Sequencing
Research Areas to Benefit Most from Next-Generation Sequencing
Greatest Technical Concern about Next-Generation Sequencing
Platforms
Greatest Computational/IT Concern
Adequate Cost/Benefit from Next-Generation Sequencing
Cost of Full Human Genome Sequence by 2010
Opinion on Platform Market Dominance
Future of Sanger Sequencing
Most Important Factors in Selecting a Next-Generation System
Opinion on Acquiring Sequence from a Service Provider
5.3. The Competitive Environment
Chapter 6: OBSERVATIONS AND CONCLUSIONS
CHAPTER 7: INTERVIEW TRANSCRIPTS
7.1. Clifford Reid, PhD, Chairman, President, & CEO, Complete
Genomics
7.2. Patrice Milos, PhD, VP & Chief Scientific Officer, Helicos
BioSciences
7.3. Steven Salzberg, PhD, Director, Center for Bioinformatics
and Computational Biology, University of Maryland
7.4. Todd Smith, PhD, Chief Science Officer, Geospiza
7.5. Anonymous Academic Researcher Active in Next-
Generation Sequencing
7.6. Stephen Naylor, PhD, CSO & Chairman, Predictive
Physiology and Medicine (PPM)
References
Company Index with Web Addresses
InsightPharmaReports.com
Related Conference
CO-LOCATED SEQUENCING CONFERENCES
CHI’s Second Annual
Next-Generation Sequencing Data Analysis
September 21–23, 2009
Rhode Island Convention Center | Providence, RI
and
CHI’s Third Annual
Exploring Next-Generation Sequencing
September 21–23, 2009
For details and to register, visit: www.healthtech.com
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