Next-Generation Sequencing: Solving the Genome

Report Description

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

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 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.

An Insight Pharma survey of next-generation sequencing system users generated a number of interesting observations and opinions, which are discussed. Transcripts from extended interviews with scientists and managers knowledgeable in the field are also included.

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

TABLES
Relative Performance of ABI, Illumina, and 454 Sequencers
Comparison of ABI, Illumina, and 454 Sequencers with Sanger Sequencing
Selected Deals in the Next-Generation Sequencing Space

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

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
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?