DNA Sequencing - technologies, markets and companies

NEW YORK, Jan. 3, 2012 /PRNewswire/ -- Reportlinker.com announces that a new market research report is available in its catalogue:

DNA Sequencing - technologies,markets and companies

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Summary

This report briefly reviews basics of human genome variations, development of sequencing technologies, and their applications. Current large and small sequencers are described as well as companies developing them. Various applications of sequencing are described including those for genetics, medical diagnostics, drug discovery and cancer. Next generation sequencing technologies, both second and third generations, are reviewed. Companies developing software for analysis of sequencing data are also included. Selected academic institutes conducting research in sequencing are also listed.

Current market is mostly for research applications and future markets will be other applications related to healthcare. The value of DNA sequencer market in 2010 is described with estimates for 2015 and 2020. Various methods and factors on which market estimates depend are described briefly. Small sequencers form the basis of SWOT (strengths, weaknesses, opportunities, threats) analysis. Several marketing strategies have been outlined.

The report includes profiles of 88 companies involved in sequencing and their 89 collaborations. The report text is supplementd by 32 tables, 9 figures and 240 selected references to the literature.

Table of Contents

0. Executive Summary 13

1. Introduction 15

Definition and scope of sequencing 15

Historical aspects of sequencing 15

Basics of molecular biology 16

DNA 16

DNA polymerases 16

Restriction endonucleases 16

DNA methylation 17

RNA 18

RNA polymerases 18

Non-coding RNAs 18

DNA transcription 19

Chromosomes 19

Telomeres 19

Mitochondrial DNA 20

Genes 20

The genetic code 21

Gene expression 21

The human genome 21

Variations in the human genome 22

Variations in DNA sequences 22

Single nucleotide polymorphisms 23

Haplotyping 23

Complex chromosomal rearrangements 24

Insertions and deletions in the human genome 24

Large scale variation in human genome 25

Variation in copy number in the human genome 25

Structural variations in the human genome 26

Transposons 27

Retrotransposon capture sequencing 27

Mapping and sequencing of structural variation from human genomes 28

Impact of sequencing on healthcare 28

2. DNA Sequencing Technologies 31

Introduction 31

DNA extraction and sample preparation 32

Apollo 300 System for next generation sequencing 32

Electrophoresis-based method 33

Ion OneTouch System 33

Microfluidics-based extraction and sample preparation 34

Pressure Cycling Technology 34

Selective immobilization of nucleic acids onto magnetic microparticles 34

Targeted and hybridization-based DNA capture 34

Sanger-sequencing technology 35

Dye-terminator sequencing 35

Large-scale sequencing 36

Automated DNA-sequencing 36

Enhancements of Sanger-sequencing 36

ABI PRISM® 310 Genetic Analyzer 37

Life Technologies' 3500 Dx genetic analyzer 37

Limitations of sequencing methods and measures to remedy them 37

High-throughput paired end transcriptome sequencing 38

Long vs short read lengths 38

Emerging sequencing technologies 38

Chemical DNA sequencing 39

Second generation sequencers 40

4300 DNA analyzer 40

Apollo 100 41

Applied Biosystems 3500 series Genetic Analyzer 41

"Color blind" approach to DNA sequencing 42

Cyclic array sequencing 42

CEQ™ 8000 42

DeepCAGE sequencing 42

Electron microscope-based DNA sequencing 43

GenometricaÔ sequencer 43

GS-FLEX system (Roche/454) 44

Background of sequencing technology 44

454 sequencing 45

GS Junior System 47

IBS sequencing technology 48

Illumina Genome Analyzer System 48

Ion Torrent's sequencing technology 49

MegaBACE 500 50

Microdroplet-based PCR for large-scale targeted sequencing. 50

Millikan sequencing 51

Multiplex amplification of human DNA sequences 51

Nanoscale sequencing 51

Polonator sequencer 52

RainStorm™ microdroplet technology 53

Sequential DEXAS 53

SOLiD system: sequencing by ligation 53

PCR-based DNA sequencing technologies 54

Bridge amplification PCR system 55

COLD-PCR and sequencing 55

Digital PCR 56

Dual primer emulsion PCR 56

Emulsion PCR 57

Multiplex PCR 57

Nucleic acid sequence-based amplification 57

Microarray-based DNA sequencing technologies 58

Arrayit's® H25K 58

High-throughput array-based resequencing 58

Human exome microarrays 59

Sequencing by hybridization 59

SOLiD-System based ChIP-Sequencing 60

Companies developing whole genome chips/microarrays 61

Next generation sequencing vs microarrays for gene expression profiling 61

Third generation sequencing 62

SOLiD4 System 62

SOLiD PI System 63

Detection of single molecules for sequencing 63

DNA sequence by use of nanoparticles 64

Denaturation mapping of DNA in nanofluidic channels 64

Helicos™ Genetic Analysis System 65

Molecular Combing 65

Nanopore sequencing 65

Optical Mapping 67

PNA-based single-molecule detection of specific DNA sequences 68

Sequencing-by-synthesis for single-molecule sequencing 69

Single molecule DNA sequencing by use of carbon nanotubes 69

Single molecule sequencing using Qdot nanocrystals 70

Single-molecule DNA sequencing in a sTOP chip nanowell 70

Single-molecule real-time sequencing 71

Single cell DNA sequencing 72

Haplotyping for whole genome sequencing 72

ImmunoSEQ technology 73

Role of bioinformatics in sequencing 74

Growth of the sequencing database 74

Data storage 74

Bioinformatics challenges of new sequencing technology 74

Bioinformatic tools for analysis of genomic sequencing data 75

Commercially available software for DNA sequencing 76

ChIA-PET tool for analysis with paired-end tag sequencing 77

Detection of CNVs and gene duplications 77

Differential expression analysis for sequence count data 77

Expression profiling without genome sequence information 78

VAAST 78

Sequencing data storage 78

Sequencing analysis tools at academic organizations 79

Accessing DNA sequence information 79

Analysis of genomic variation by sequencing of large populations 80

Fund of research into interpretation of sequencing data 80

Future challenges for managing sequencing data 80

3. Comparative Analysis of Sequencing Technologies 83

General findings of the study 83

Sanger versus second generation marketed sequencers 83

Common features and differences among second generation sequencers 83

Third generation large sequencers 84

SOLiD4 versus competing large sequencers 84

Illumina's HiSeq and MiSeq sequencers 85

The ideal small sequencer 86

SWOT analysis of small sequencers 86

Concluding remarks on SWOT analysis 88

4. Research Applications of Sequencing 91

Introduction 91

Applications in basic research 92

ChIA-PET technology for 3D study of the genome 92

ChIP-Seq for study of gene expression 92

Chromatin profiling by direct DNA sequencing 93

Discovery of immunoglobulin gene by pyrosequencing 93

Epigenetic modifications analyzed by next generation sequencing 93

Exome sequencing for study of human variation 93

Genome sequencing with combinatorial probe anchor ligation 94

GS-FLX sequencing for simultaneous detection of mutation and CNV 94

Identifying protein-coding genes in genomic sequences 94

mRNA sequencing 95

Mutation rate measured by direct sequencing 96

Protein-protein interactome network mapping 96

Sequencing the transcriptomes of stem cells 97

Sequencing and synthetic biology 97

Synthetic sequence in a bacterial cell 97

Functional synthetic proteins 98

Sequencing of human genomes 98

Whole genome sequencing 98

Whole-genome sequencing of methylome 98

Whole genome resequencing 99

Personal genome sequencing 99

Sequencing 1000 human genomes 100

Missing human genome sequences 100

Role of sequencing in identification of human remains 101

Sequence map of the human pan-genome 101

Sequencing of African genomes 102

Sequencing of Korean genomes 102

Sequencing mitochondrial genome 103

Sequencing of ancient genomes 103

Saqqaq genome 103

Neandertal genome 104

Future prospects of human genome sequencing 104

Sequencing genomes of non-human primates 104

Sequencing genomes of other organisms 105

Sequencing of the mouse genome 105

Sequencing of the dog genome 106

Sequencing the turkey genome 107

Sequencing of the frog genome 107

Sequencing the genome of body louse 108

Sequencing of the ant genome 108

Sequencing of the genome of water flea 109

Applications in drug discovery and development 109

Resequencing 109

RNA profiling 110

Transcriptome sequencing for mRNA Expression 111

RNA splice variants 111

Quantitative selection of aptamers through sequencing 112

Sequencing projects supported by US Government 112

NHGRI's sequencing initiatives 112

JGI's Community Sequencing Program 112

Approved medical sequencing projects 113

1000 Genomes Project 113

Findings of some studies of the 1000 genomes project 114

HapMap catalog as a foundation 115

Role of SOLiD™ System in 1000 Genomes Project 115

Concluding remarks 115

Human Variome Project 115

Academic centers conducting research on sequencing 116

Important academic collaborations 117

Scientific manpower for sequencing 118

Large-scale genomic sequencing projects at Joint Genome Institute 118

5. Applications of Sequencing in Healthcare 121

Introduction 121

Applications of sequencing in molecular diagnostics 121

Next generation sequencing for detection of solid organ transplant rejection 122

Applications of sequencing in oncology 122

A project to assess sequencing technologies for tumor DNA 123

Amplicon sequencing in cancer 123

Cancer Genome Atlas 123

Detection of cancer biomarkers 124

Sequencing mitochondrial DNA to identify cancer biomarkers 124

Biomarkers for personalizing cancer treatment 125

Digital proteomics for cancer profiling 126

Epigenome profiling 126

Gaining insights into mutational processes 126

Multiplexed cancer gene mutation analysis 127

NGS-based molecular profiling of cancer in FFPE specimens 127

Paired-end sequencing 128

Pathology tissue-ChIP 129

RNA-Seq to study cancer transcriptome 129

Sequencing cancer cell lines 129

Sequencing for studying chromothripsis in cancer 130

Sequencing of complex human cancer genomes 130

Sequencing single cells to study evolution of cancer 130

Sequencing for assessing resistance to anticancer therapy 131

Sequencing in various types of malignancies 131

Brain tumors 131

Breast cancer 132

Hematological malignancies 134

Hepatocellular carcinoma 135

Melanoma 135

Ovarian cancer 136

Prostate cancer 136

Sequencing in genetic disorders 137

Array-based whole-exome sequencing in Bartter syndrome 137

Detection of X-linked disorder due to N-terminal acetyltransferase deficiency 137

DNA sequencing of maternal plasma for detection of fetal aneuploidy 138

Exome sequencing for genetic disorders 139

Discovery of the gene for Miller syndrome 139

Discovery of the gene for Kabuki syndrome 139

Familial combined hypolipidemia 140

Familial thoracic aortic aneurysm 140

Proteus syndrome 140

Sequencing for study of transposons 140

Sequencing of whole genome in Charcot-Marie-Tooth disease 141

Sequencing in muscular dystrophy 141

Sequencing in Huntington's disease 141

Sequencing genomes of the newborn to screen for genetic disorders 142

Study of rare variants in pinpointing disease-causing genes 143

Whole genome sequencing for diagnosis of genetic disorders 143

Sequencing for HLA typing 144

Sequencing for study of the human immune system 144

Sequencing in neurological disorders 145

Sequencing for mutations associated with autism spectrum disorders 145

Sequencing in attention-deficit/hyperactivity disorder 145

Sequencing genomes of microbes 146

DNA sequencing for study of bacterial epidemics 146

Human Microbiome Project 148

Pyrosequencing of microbial flora in leg ulcers 149

Sequencing of gut microbes in obesity 149

Sequencing for mapping genomic variation in Mycobacterium ulcerans 150

Sequencing for mapping genetic interactions in bacteria 150

Sequencing of DNA from single cells of bacteria 150

Sequencing of the Candida genome 151

Sequencing of human salivary microbiome 152

Sequencing in the management of HIV/AIDS 152

Sequencing in the management of HBV 153

Sequencing in the management of HCV 154

Sequencing genome of Lassa fever virus 154

Surveillance of H1N1 influenza A virus using resequencing arrays 155

Population targeted sequencing studies 155

Sequencing in aging research 156

Next generation sequencing and pharmaceutical industry 156

Next generation sequencing and drug design and discovery 156

Next generation sequencing and drug safety 156

Next generation sequencing for antibacterial therapeutic discovery 157

Applications of human transcriptome array in clinical trials 157

Role of sequencing in personalized medicine 158

Whole genome sequencing and personalized medicine 158

Role of sequencing in personalized cancer management 159

Standardization of sequencing for personalized medicine 159

Future of sequencing and personalized medicine 160

Future prospects of next generation sequencing 161

Devices for next generation sequencing 161

Clinical applications of NGS 161

6. Markets for Sequencers 163

Introduction 163

Methods used for estimation of sequencer markets 163

Currently marketed sequencers 163

Academic and research markets for sequencing 163

Factors affecting future development of sequencing markets 164

Future needs and support of research 164

Bioinformatics in relation to sequencing 164

Reducing the cost of human genome sequencing 165

US Government-supported research on sequencing 165

Contribution of American Recovery and Reinvestment Act 167

Genome X Prize Foundation 167

Innovations to reduce cost of whole genome sequencing 168

Commercial prospects of low cost genome sequencing 168

Genome sequencing suitable for personalized medicine 168

The global sequencing market 169

Marketing potential for sequencers 170

Challenges to developing market for sequencers 171

Recommendations 171

7. Companies Involved in Sequencing 173

Introduction 173

Collaborations 280

8. References 285

Tables

Table 1?1: Historical landmarks in DNA sequencing 15

Table 1?2: Genetic variations in the human genome 22

Table 2?1: ChIP detection platforms for sequencing 60

Table 2?2: Companies developing whole genome chips/microarrays 61

Table 2?3: Systems for single molecule sequencing 64

Table 2?4: Companies providing DNA sequencing software 76

Table 3?1: Comparison of a generation I and generation II sequencers 83

Table 3?2: Similarities and differences between second generation sequencers 84

Table 3?3: SWOT of ABI 310 86

Table 3?4: SWOT of IBS sequencing 87

Table 3?5: SWOT of NABsys' Hybridization-Assisted Nanopore Sequencing 87

Table 3?6: SWOT of 4300 DNA Analysis System Li-Cor 87

Table 3?7: SWOT of Genometrica 87

Table 3?8: SWOT of Polonator 87

Table 3?9: SWOT of GS FLEX Junior 88

Table 3?10: SWOT of Oxford Nanopore Technologies' nanopore DNA sequencing 88

Table 3?11: SWOT of Ion Torrent™ Personal Genome Machine 88

Table 3?12: SWOT of Pacific BioSciences' single-molecule real-time sequencing 88

Table 4?1: Number of genes in organisms with fully sequenced genomes 91

Table 4?2: Approved medical sequencing projects 113

Table 4?3: Academic centers conducting research on DNA sequencing 116

Table 4?4: Distribution of scientific manpower for sequencing 118

Table 5?1: Companies involved in application of sequencing in molecular diagnostics 121

Table 6?1: Marketed next generation sequencers 163

Table 6?2: De novo sequencing vs resequencing markets 164

Table 6?3: Global markets for sequencing services according to geographical regions 169

Table 6?4: Global markets for sequencing services according to applications 169

Table 6?5: Global markets for sequencers from 2011 to 2021 171

Table 7?1: Companies developing in sequencing technologies and instruments 173

Table 7?2: Companies that provide sequencing services 174

Table 7?3: Companies that provide bioinformatics support for sequencing 175

Table 7?4: Selected collaborations for DNA sequencing 280

Figures

Figure 2?1: DNA sequencing process 32

Figure 2?2: Comparison of traditional sequencing and next generation sequencing 39

Figure 2?3: Watson-Crick base pairing 40

Figure 2?4: Genome Sequencer FLX system(Roche/454) 45

Figure 2?5: Workflow of Genome Sequenser FLX system 46

Figure 2?6: Sequencing by ligation 54

Figure 2?7: Construction of SOLiD fragment library using DNA enrichment by ChIP 60

Figure 2?8: Single molecule, realtime DNA sequencing 71

Figure 5?1: Role of sequencing in the development of personalized medicine 158

Figure 6?1: Global markets for sequencing services according to applications 170

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