SYS-CON MEDIA Authors: Greg Ness, Sean Houghton, Glenn Rossman, Ignacio M. Llorente, Xenia von Wedel

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DNA Sequencing - Technologies, Markets and Companies

DUBLIN, Feb. 12, 2014 /PRNewswire/ --Research and Markets (http://www.researchandmarkets.com/research/l54sxm/dna_sequencing) has announced the addition of Jain PharmaBiotech's new report "DNA Sequencing - Technologies, Markets and Companies" to their offering.

(Logo: http://photos.prnewswire.com/prnh/20130307/600769)

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 2013 is described with estimates for 2018 and 2023. Various methods and factors on which market estimates depend are described briefly. Markets are tabulated according to geographical areas as well as applications. Small sequencers form the basis of SWOT (strengths, weaknesses, opportunities, threats) analysis. Several marketing strategies have been outlined.

The report includes profiles of 111 companies involved in sequencing and their 115 collaborations. The report text is supplementd by 38 tables, 13 figures and 350 selected references to the literature.
Key Topics Covered:

0. Executive Summary

1. Introduction
Definition and scope of sequencing
Historical aspects of sequencing
Basics of molecular biology
DNA
DNA polymerases
Restriction endonucleases
DNA methylation
RNA
RNA polymerases
Non-coding RNAs
DNA transcription
Chromosomes
Chromosome sequences
Telomeres
Mitochondrial DNA
Genes
The genetic code
Gene expression
The human genome
ENCODE
The exome
The epigenome
Human Epigenome Atlas
Variations in the human genome
Variations in DNA sequences
Single nucleotide polymorphisms
Haplotyping
Complex chromosomal rearrangements
Insertions and deletions in the human genome
Large scale variation in human genome
Variation in copy number in the human genome
Structural variations in the human genome
Transposons
Retrotransposon capture sequencing
Mapping and sequencing of structural variation from human genomes
Impact of sequencing on healthcare

2. DNA Sequencing Technologies
Introduction
DNA extraction and sample preparation
Apollo 300 System for next generation sequencing
Electrophoresis-based method
Ion OneTouch System
Microfluidics-based extraction and sample preparation
Pressure Cycling Technology
Selective immobilization of nucleic acids onto magnetic microparticles
Targeted and hybridization-based DNA capture
Sanger-sequencing technology
Dye-terminator sequencing
Large-scale sequencing
Automated DNA-sequencing
Enhancements of Sanger-sequencing
ABI PRISM® 310 Genetic Analyzer
Life Technologies' 3500 Dx genetic analyzer
Limitations of sequencing methods and measures to remedy them
High-throughput paired end transcriptome sequencing
Long vs short read lengths
Validation of NGS data
Emerging sequencing technologies
Chemical DNA sequencing
Second generation sequencers
4300 DNA analyzer
Apollo 100
Applied Biosystems 3500 series Genetic Analyzer
"Color blind" approach to DNA sequencing
Cyclic array sequencing
CEQ 8000
DeepCAGE sequencing
Electron microscope-based DNA sequencing
GS-FLEX system (Roche/454)
Background of sequencing technology
454 sequencing
IBS sequencing technology
Illumina Genome Analyzer System
MiSeqDx
Ion Torrent's sequencing technology
MegaBACE 500
Microdroplet-based PCR for large-scale targeted sequencing.
Millikan sequencing
Multiplex amplification of human DNA sequences
Nanoscale sequencing
Polonator sequencer
RainStorm microdroplet technology
Sequential DEXAS
SOLiD system: sequencing by ligation
PCR-based DNA sequencing technologies
Bridge amplification PCR system
COLD-PCR and sequencing
Digital PCR
Dual primer emulsion PCR
Emulsion PCR
Multiplex PCR
Non-PCR based sequencing
Nucleic acid sequence-based amplification
Microarray-based DNA sequencing technologies
Arrayit's® H25K
High-throughput array-based resequencing
Human exome microarrays
Sequencing by hybridization
SOLiD-System based ChIP-Sequencing
Companies developing whole genome chips/microarrays
Next generation sequencing vs microarrays for gene expression profiling
Third generation sequencing
SOLiD4 System
SOLiD PI System
Detection of single molecules for sequencing
DNA sequence by use of nanoparticles
Denaturation mapping of DNA in nanofluidic channels
Helicos Genetic Analysis System
Molecular Combing
Nanopore sequencing
Optical Mapping
Nanopore-based single-molecule detection of specific DNA sequences
Sequencing-by-synthesis for single-molecule sequencing
Single molecule DNA sequencing by use of carbon nanotubes
Single molecule sequencing using Qdot nanocrystals
Single-molecule DNA sequencing in a sTOP chip nanowell
Single-molecule real-time sequencing
Single cell DNA sequencing
MALBAC for single cell DNA sequencing
Single cell sequencing of uncultured microbes
Single-sperm sequencing
Thermosequencing
Whole genome sequencing for haplotyping
Mitochondrial exome sequencing
ImmunoSEQ technology
Future prospects of next generation sequencing
Devices for NGS
Reduction of errors in NGS
Artifactual mutations during the sample preparation process
Duplex sequencing

3. Role of Bioinformatics in Sequencing
Introduction
Growth of the sequencing database
Sequencing data storage
Bioinformatics challenges of new sequencing technology
DNA libraries for NGS
Bioinformatic tools for analysis of genomic sequencing data
Software for DNA sequencing
Software from academic and open sources
Commercial software for sequencing
ChIA-PET tool for analysis with paired-end tag sequencing
Compressive genomics
Detection of CNVs and gene duplications
Detection of SVs in massively parallel sequencing data
Differential expression analysis for sequence count data
Expression profiling without genome sequence information
Ion Reporter Software
Opal platform
VAAST
knoSYSTM100
Accessing DNA sequence information
Analysis of genomic variation by sequencing of large populations
Analysis of rare variants in NGS studies
Human gene connectome
Funding of research for interpretation of sequencing data
Future challenges for managing sequencing data

4. Comparative Analysis of Sequencing Technologies
General findings of the study
Sanger versus second generation marketed sequencers
Common features and differences among second generation sequencers
Third generation large sequencers
SOLiD4 versus competing large sequencers
Illumina's HiSeq sequencer
Third generation small sequencers
Genometrica? desk top sequencer
Illumina's MiSeq sequencer
Roche/454 GS Junior System
Life Technologies' Benchtop Ion Proton Sequencer
Oxford Nanopore's MinION system
The ideal small sequencer
SWOT analysis of small sequencers
Concluding remarks on SWOT analysis

5. Sequencing for Research
Introduction
Applications in basic research
ChIA-PET technology for 3D study of the genome
ChIP-Seq for study of gene expression
Chromatin profiling by direct DNA sequencing
Discovery of immunoglobulin gene by pyrosequencing
Epigenetic modifications analyzed by next generation sequencing
Exome sequencing for study of human variation
Genome sequencing with combinatorial probe anchor ligation
Identifying protein-coding genes in genomic sequences
mRNA sequencing
Mutation rate measured by direct sequencing
Protein-protein interactome network mapping
Sequencing for the study of microchimerism
Sequencing for the study of CNVs
CNVnator
GS-FLX sequencing for simultaneous detection of mutations and CNVs
Sequencing the transcriptomes of stem cells
Sequencing and synthetic biology
Synthetic sequence in a bacterial cell
Functional synthetic proteins
Sequencing of human genomes
Whole genome sequencing
Whole-genome sequencing of methylome
Whole genome resequencing
Personal genome sequencing
Sequencing 1000 human genomes
Saudi Arabian human genome program
Missing human genome sequences
Role of sequencing in identification of human remains
Sequence map of the human pan-genome
Sequencing of African genomes
Sequencing of Korean genomes
Sequencing mitochondrial genome
Sequencing of ancient genomes
Saqqaq genome
Neandertal genome
Hominin genome
Future prospects of human genome sequencing
Sequencing genomes of non-human primates
Sequencing of chimpanzee genome
Sequencing of macaque genome
Sequencing of gorilla genome
Sequencing genomes of other organisms
Species biodiversity study by the Canadian Centre for DNA Barcoding
Ant genome
Bat genome
Body louse genome
Camel genome
Dog genome
Frog genome
Goat genome
Mouse genome
Tibetan antelope genome
Turkey genome
Water flea genome
Whale genome
Applications in drug discovery and development
Resequencing
RNA profiling
Transcriptome sequencing for mRNA Expression
RNA splice variants
Quantitative selection of aptamers through sequencing
Sequencing projects supported by US Government
NHGRI's sequencing initiatives
JGI's Community Sequencing Program
NIH funding for interpreting sequence variants in the human genome
NIH to fund studies of gene-environmental interactions in human diseases
Approved medical sequencing projects
1000 Genomes Project
Findings of some studies of the 1000 genomes project
HapMap catalog as a foundation
Role of SOLiD System in 1000 Genomes Project
Protection of privacy of participants in 100 Genomes project
Concluding remarks
Human Variome Project
Academic centers conducting research on sequencing
The New York Genome Center
Important academic collaborations
Scientific manpower for sequencing
Large-scale genomic sequencing projects at Joint Genome Institute

6. Applications of Sequencing in Healthcare
Introduction
Applications of sequencing in molecular diagnostics
Guidelines for use of sequencing for diagnosis
HLA sequencing for patient stratification
Next generation sequencing for detection of solid organ transplant rejection
Next generation sequencing for forensic diagnosis
Companies developing sequence-based molecular diagnostics
Applications of sequencing in oncology
A project to assess sequencing technologies for tumor DNA
Amplicon sequencing in cancer
Cancer Genome Atlas
Detection of cancer biomarkers
Sequencing mitochondrial DNA to identify cancer biomarkers
Biomarkers for personalizing cancer treatment
Digital proteomics for cancer profiling
Epigenome profiling
Exosome sequencing
Gaining insights into mutational processes
High throughput sequencing for anticancer drug discovery
Multiplexed cancer gene mutation analysis
NGS-based molecular profiling of cancer in FFPE specimens
Paired-end sequencing
Pathology tissue-ChIP
RNA-Seq to study cancer transcriptome
Sequencing cancer cell lines
Sequencing for studying chromothripsis in cancer
Sequencing of complex human cancer genomes
Sequencing for identification of FGFR gene fusions in cancer
Sequencing single cells to study evolution of cancer
Sequencing for assessing resistance to anticancer therapy
Sequencing of brain tumors
Sequencing for genetic alterations in gliomas
Sequencing for genetic alterations in medulloblastoma
Sequencing of breast cancer
BRCA mutations
Circulating nucleic acids as biomarkers of cancer
Deep sequencing of miRNA for signatures of invasiveness
NGS reveals heterogeneity of breast cancer
Sequencing of breast cancer metastases
Triple negative breast cancer
Whole genome sequencing in breast cancer
Sequencing of colorectal cancer
Sequencing of head and neck cancer
NGS for detection of HPV sequences in carcinoma of oropharynx
Sequencing of hematological malignancies
Myelodysplastic syndromes
Acute myeloid leukemia
Acute promyelocytic leukemia
Chronic myelomonocytic leukemia
Hairy-cell leukemia
Sequencing in chronic neutrophilic leukemia and atypical CML
Sequencing in hepatocellular carcinoma
Sequencing of melanoma
Sequencing of ovarian cancer
Sequencing of prostate cancer
Identification of mutations in prostate cancer by exome sequencing
Future prospects and challenges of NGS applications in oncology
Sequencing in genetic disorders
Approaches to sequencing in genetic disorders
High-throughput sequencing in Undiagnosed Disease Program at NIH
Sequencing of maternal plasma for detection of fetal aneuploidy
Sequencing for study of transposons
Sequencing genomes of the newborn to screen for genetic disorders
Study of rare variants in pinpointing disease-causing genes
Whole exome sequencing for diagnosis of Mendelian disorders
Whole genome sequencing for diagnosis of genetic disorders
Whole genome sequencing of a human fetus from maternal plasma
Genetic disorders investigated by sequencing
CHARGE syndrome
DiGeorge syndrome
Discovery of the gene for Miller syndrome
Discovery of the gene for Kabuki syndrome
Familial combined hypolipidemia
Familial thoracic aortic aneurysm
Hereditary blindness
Proteus syndrome
Syndrome of hypogonadotropic hypogonadism, ataxia, and dementia
Whole-exome sequencing in Bartter syndrome
X-linked disorder due to N-terminal acetyltransferase deficiency
Sequencing for HLA typing
High-throughput HLA genotyping with deep sequencing
Sequencing for study of the human immune system
Sequencing for investigating drug-virome interactions in organ transplants
Sequencing in neurological and psychiatric disorders
Sequencing in Alzheimer disease
Sequencing in Parkinson disease
Sequencing in Huntington's disease
Sequencing in Wilson's disease
Sequencing for mutations in familial amyotrophic lateral sclerosis
Sequencing of whole genome in Charcot-Marie-Tooth disease
Sequencing in muscular dystrophy
Sequencing in acute brain injury due to hemorrhage
Sequencing for mutations associated with autism spectrum disorders
Sequencing for diagnosis of intellectual disability
Sequencing in neurodevelopmental disorders
NGS for identifying mutations in RNA gene
Sequencing in attention-deficit/hyperactivity disorder
Sequencing in schizophrenia and bipolar disorder
Sequencing in cardiovascular disorders
Inherited cardiomyopathies
Sequencing genomes of microbes
DNA sequencing for study of bacterial epidemics
Role of sequencing in cholera epidemics
Role of sequencing in epidemic of Shiga toxin-producing E. coli
Role of whole genome sequencing in identification of C. difficile
Sequencing study of Salmonella emergence in Sub-Saharan Africa
Sequencing of ancient specimes from past epidemics
Human Microbiome Project
Pyrosequencing of microbial flora in leg ulcers
Sequencing the human gut microbiome for new immunomodulatory molecules
Sequencing of gut microbes in obesity
Sequencing for mapping genomic variation in Mycobacterium ulcerans
Sequencing for mapping genetic interactions in bacteria
Sequencing for study of antibiotic resistance in bacteria
Sequencing of DNA from single cells of bacteria
Sequencing of the fungal genomes
Sequencing for detection of drug resistance in Plasmodium falciparum
Sequencing of human salivary microbiome
Sequencing in the management of HIV/AIDS
Sequencing plus immunological analyses to study HIV evolution
NGS for studying neuroAIDS
Surveillance of drug resistance in HIV-infected individuals
Sequencing in the management of HBV
Sequencing in the management of HCV
Sequencing genome of Lassa fever virus
Sequencing genome of a rhabdovirus associated with acute hemorrhagic fever
Surveillance of H1N1 influenza A virus using resequencing arrays
Whole-genome sequencing for investigation of MRSA outbreaks
Role of sequencing in tracking a hospital infection of Klebsiella pneumoniae
Population targeted sequencing studies
Sequencing in aging research
Next generation sequencing and pharmaceutical industry
Next generation sequencing and drug design and discovery
Next generation sequencing and drug safety
Next generation sequencing for antibacterial therapeutic discovery
Applications of human transcriptome array in clinical trials
Role of sequencing in personalized medicine
Whole genome sequencing and personalized medicine
Whole exome sequencing and personalized disease risk
Personal Genome Project
Role of sequencing in personalized cancer management
Standardization of sequencing for personalized medicine
Future of sequencing and personalized medicine
Current status and future prospects of clinical applications of NGS
Challenges for clinical applications of NGS
Rare Diseases Genomes Project
Ethical aspects of sequencing

7. Markets for Sequencers
Introduction
Methods used for estimation of sequencer markets
Currently marketed sequencers
Academic and research markets for sequencing
Factors affecting future development of sequencing markets
Future needs and support of research
Bioinformatics in relation to sequencing
Reducing the cost of human genome sequencing
US Government-supported research on sequencing
Contribution of American Recovery and Reinvestment Act
Genome X Prize Foundation
Innovations to reduce cost of whole genome sequencing
Commercial aspects of low cost genome sequencing
Genome sequencing suitable for personalized medicine
The global sequencing markets
Sequencing markets according to applications
Sequencing markets according to therapeutic areas
Marketing potential for sequencers
Challenges to developing market for sequencers
Recommendations

8. Companies Involved in Sequencing
Introduction
Major players in sequencing
Profiles of companies involved in sequencing
Collaborations

9. References

Tables

Table 1-1: Historical landmarks in DNA sequencing
Table 1-2: Genetic variations in the human genome
Table 2-1: ChIP detection platforms for sequencing
Table 2-2: Companies developing whole genome chips/microarrays
Table 2-3: Systems for single molecule sequencing
Table 3-1: Software programs for sequencing from open sources
Table 3-2: Companies providing DNA sequencing software
Table 4-1: Comparison of a generation I and generation II sequencers
Table 4-2: Similarities and differences between second generation sequencers
Table 4-3: SWOT of ABI 310
Table 4-4: SWOT of IBS sequencing
Table 4-5: SWOT of NABsys' Hybridization-Assisted Nanopore Sequencing
Table 4-6: SWOT of 4300 DNA Analysis System Li-Cor
Table 4-7: SWOT of Genometrica
Table 4-8: SWOT of Polonator
Table 4-9: SWOT of GS FLEX Junior
Table 4-10: SWOT of Oxford Nanopore's MinION system
Table 4-11: SWOT of Ion Torrent Personal Genome Machine
Table 4-12: SWOT of Pacific BioSciences' single-molecule real-time sequencing
Table 4-13: SWOT of Illumina's miSeq
Table 4-14: SWOT of QIAGEN's GeneReader sequencer
Table 4-15: SWOT of GnuBio's microfluidics-based sequencing system
Table 5-1: Number of genes in organisms with fully sequenced genomes
Table 5-2: Approved medical sequencing projects
Table 5-3: Academic centers conducting research on DNA sequencing
Table 5-4: Distribution of scientific manpower for sequencing
Table 6-1: Companies involved in application of sequencing in molecular diagnostics
Table 7-1: Marketed next generation sequencers
Table 7-2: De novo sequencing vs resequencing markets
Table 7-3: Global markets for sequencing services according to geographical regions
Table 7-4: Global markets for sequencing services according to applications
Table 7-5: Sequencing markets according to therapeutic areas
Table 7-6: Global markets for sequencers from 2013 to 2023
Table 8-1: Companies developing sequencing technologies and instruments
Table 8-2: Companies that provide sequencing services
Table 8-3: Companies that provide bioinformatics support for sequencing
Table 8-4: Major players in sequencing
Table 8-5: Selected collaborations for DNA sequencing

Figures

Figure 2-1: DNA sequencing process
Figure 2-2: Comparison of traditional sequencing and next generation sequencing
Figure 2-3: Watson-Crick base pairing
Figure 2-4: Genome Sequencer FLX system (Roche/454)
Figure 2-5: Workflow of Genome Sequenser FLX system
Figure 2-6: Sequencing by ligation
Figure 2-7: Construction of SOLiD fragment library using DNA enrichment by ChIP
Figure 2-8: Nanopore-based sequence-specific detection of DNA
Figure 2-9: Single molecule, realtime DNA sequencing
Figure 2-10: A scheme of thermosequencing platform
Figure 6-1: Role of sequencing in the development of personalized medicine
Figure 7-1: Cost of sequencing per genome
Figure 7-2: Global markets for sequencing services according to applications

Author

Professor K. K. Jain is a neurologist/neurosurgeon by training and has been working in the biotechnology/biopharmaceuticals industry for several years. He received graduate training in both Europe and USA, has held academic positions in several countries and is a Fellow of the Faculty of Pharmaceutical Medicine of the Royal Colleges of UK. Currently he is a consultant at Jain PharmaBiotech. Prof. Jain is the author of 415 publications including 16 books (2 as editor) and 48 special reports, which have covered important areas in biotechnology, gene therapy and biopharmaceuticals.

For more information visit http://www.researchandmarkets.com/research/l54sxm/dna_sequencing

Source: Jain PharmaBiotech

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