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In this section, new technologies in the genomics field will be displayed:
Fourth Generation DNA Sequencing Technologies:
This DNA sequencing technology is scalable, and it uses low-cost semiconductor manufacturing techniques to make an integrated circuit able to directly perform non-optical DNA sequencing of genomes. Sequence data can be obtained by directly sensing the ions produced by template-directed DNA polymerase synthesis using all-natural nucleotides on a massively parallel semiconductor-sensing device or ion chip (for more details see the scientific article "An integrated semiconductor device enabling non-optical genome sequencing" published by Rothberg JM et al.).
The concept of using a nanopore as a biosensor was first proposed in the mid 1990s when nanopores were starting to be researched at academic institutions such as Oxford, Harvard and UCSC - which were all Oxford Nanopore collaborators. In an industrial setting, Oxford Nanopore was founded in 2005 in England to translate nanopore science into an electronics-based technology.The end-to-end system includes sample preparation, molecular analysis and informatics, and is designed to provide disruptive user benefits in a number of applications. See more details in the article "Oxford Nanopore announcement sets sequencing sector abuzz" by Eisenstein M on Nature Biotechnology.
New DNA sequencing technologies:
The advent of new DNA sequencing technologies had a significant impact in the genomics field. We now face the same problems as computer scientists since the cost per DNA sequencing reaction has dropped significantly but Moore's law still prevails (1). The main idea is to cut costs and be able to sequence one genome for less than a 1000 dollars. Recently, several new sequencing instruments were released and had already transformed the field. Some of these new technologies will be described here and links to each company that provides them will be displayed:
Second generation DNA sequencers:
This was the first commercially available instrument introduced in 2004. This sequencer works on the principle of the "pyrosequencing reaction" which uses the pyrophosphate molecule released by DNA polymerase in the DNA synthesis (1). This molecule is later converted into light and can be detected. Each run takes 7 days and it can generate 100 Mb with fragments having on average 250bp.
This instrument was released in October of 2007 and it uses a unique sequencing process catalyzed by DNA ligase (1). Each SOLiD (Sequencing by Oligo Ligation and Detection) run requires 5 days and produces 3-4 Gb (the size of the human genome) of sequence with an average read length of 25-35bp.
Introduced in 2006, the Illumina Genome Analyzer is based on the concept of "sequencing by synthesis" (SBS) to produce sequence reads of 32-40bp in 4 days (1). This technology can generate 1.3 Gb of DNA sequence.
Dover Systems, in collaboration with Dr George Church's Laboratory of Harvard Medical School developed the Polonator G.007, a revolutionary approach to second-generation sequencing. The Polonator G.007 is a completely open platform, combining a high performance instrument at a very low price point, with freely downloadable, open-source software and protocols, low-cost, off-the-shelf reagents, and inexpensive flow cells.
Third generation DNA sequencers:
Pacific Biosciences was funded in 2004 with main the goal of developing Single-Molecule, Real-Time (SMRT) DNA sequencing technology. The company's approach is based on eavesdropping on a single DNA polymerase molecule working in a continuous, processive manner. Distinguished by its long reads, short run times, and high quality sequence data with less effort and costs, SMRT DNA sequencing promises to be a transformative technology that will enable a new paradigm in genome analysis.
The Helicos™ Genetic Analysis System is the first technology capable of true direct DNA measurement available to the scientific community. The system is comprised of the HeliScope™ Single Molecule Sequencer, the HeliScope™ Analysis Engine, and the HeliScope™ Sample Loader.
Complete Genomics was established in March 2006 by Dr. Clifford Reid, Dr. Radoje Drmanac, and John Curson, who shared a vision to provide high-throughput, affordable, complete genome sequencing of human populations.This company is developing a novel DNA sequencing platform mainly based on a range of proprietary biochemistry, nanotechnology, instrumentation and computing technologies.
1. Mardis ER. The impact of next generation sequencing technology on genetics. Trends Genet. (3) 133-141, 2008.
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