Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Solexa Completes First Full Genome Sequence with Cluster-SBS Technology

10.03.2005


Results Provide End-to-End Experimental Demonstration of Future DNA Sequencing Technology, Lay Groundwork for Human Re-sequencing



Solexa today announced the completion of its first genome sequence, that of the virus Phi-X 174. The company announced genome coverage of 100%, accuracy of at least 99.93% and the detection of at least three mutations subsequently confirmed by conventional DNA sequencing techniques. This accuracy was achieved despite a number of sub-sequences, which are particularly difficult to sequence with certain other chemistries.

The work reported by Solexa today was completed using its breakthrough/completely novel sequencing biochemistry. This work provides end-to-end demonstration of a technology expected to sequence the DNA of individual humans for the detection of key disease-predisposing mutations. The genome sequence has already been repeated a number of times.


Over 1,000-times improvement in data generated per sample preparation

While the Phi-X 174 genome sequenced was small at just over 5,000 bases, the amount of sequence data generated was considerably larger. Whereas conventional DNA sequencing equipment typically delivers no more than approximately 1,200 bases per sample preparation, this Solexa experiment delivered more than three million bases from a single sample preparation. Thus sample preparation, which can be a major effort in large-scale DNA sequencing projects, can potentially be reduced by over 1,000-fold.

While impressive, these results significantly underestimate the amount of data available. In these experiments, because of the prototype nature of the hardware used, the instrument system was directed to image only 3% of the available area in its flow-cell. Thus the company estimates that more than 100 million bases of data were represented in a single flow cell, all from a single sample preparation. Solexa expects future experiments to substantially increase the fraction of data to be recovered. Ultimately later this year fully automated instrumentation is expected to allow hands-off capture of almost all available data.

Cluster technology, acquired in 2004, achieves record small feature sizes

The experiments being reported today all were conducted using DNA cluster technology, which was acquired by the company in early 2004 and has been significantly refined and developed since that time. Notably, the results were implemented with proprietary surface chemistry developed by the company. This approach has successfully achieved clusters so small that they are beyond the resolving power of the research microscope used to observe them. This achievement confirms Solexa’s decision to move from earlier bead based work to clusters. The new approach provides high fluorescence signals while achieving submicron feature sizes, thereby enabling rapid and inexpensive detection of large numbers of DNA sequencing data points. Since instrument depreciation is a major contributor to the cost per data point, this is an important advancement. By lowering instrument costs per data point while simultaneously achieving extremely low reagent usage, the company anticipates that cluster technology may result in substantially lower sequencing costs.

While companies with competing technologies have developed novel DNA sequencing technologies based on beads spaced by as much as 50 microns apart, Solexa is now working with clusters as small as one-half a micron in radius. This density of sequence reads is up to 500 times higher than the bead-based approach. Thus reagent costs can be expected to scale in parallel, likely giving Solexa a substantial long-term cost advantage.

Sequencing By Synthesis (SBS) provides read lengths needed for future human re-sequencing

Since Solexa was founded, it has labored to increase the read length of the sequences it is able to determine. Bioinformatics analysis of the human genome reference sequence has shown that read lengths of 25 base pairs are the point of diminishing returns for increasing read-lengths in genome-scale re-sequencing work. At this level, up to 82% of the human genome can be uniquely associated with specific reads, even when those reads record mutations. Above this level, the percentage of the genome covered increases very slowly with increasing read length, due to the content of highly repetitive sequences (i.e., those of least importance to most researchers). Solexa has now achieved this read length in the Phi-X experiment and has obtained greater than a hundred thousand reads of this length on a wide range of sequence contexts. The sequencing technology is not fundamentally limited to this read length.

The sequence covered by Solexa in this demonstration of the “Cluster-SBS” technology includes a numbers of cases in which the same nucleotide occurs for many consecutive positions, a type of subsequence that can be problematic for other sequencing chemistries. The Solexa SBS chemistry reads through these by analysis of each incremental base in a stepwise fashion. This focus on accuracy is expected to be a key competitive advantage for the company. Re-sequencing is often used to look for very rare mutations, particularly in cancer samples. In these and other cases, even a modest error rate can create more false positives than real detected mutations.

The Pioneering Role of Phi-X 174

In making this announcement, the company noted that the Phi-X 174 virus was again playing a pioneering role. The first complete sequence of a genome was ØX174 in 1978 by Fred Sanger and co-workers (J. Mol. Biol., 125, 225-246, 1978). He shared the Nobel Prize for Chemistry in 1980 for "...contributions concerning the determination of base sequences in nucleic acids". More recently, the first complete synthesis of a genome was described with ØX174 by Craig Venter et al in 2003 (Proc. Natl. Acad. Sci. USA., 100, 15440-15445, 2003).

Rowan Minnion | alfa
Further information:
http://www.solexa.com

More articles from Life Sciences:

nachricht Scientists enlist engineered protein to battle the MERS virus
22.05.2017 | University of Toronto

nachricht Insight into enzyme's 3-D structure could cut biofuel costs
19.05.2017 | DOE/Los Alamos National Laboratory

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

Im Focus: Bacteria harness the lotus effect to protect themselves

Biofilms: Researchers find the causes of water-repelling properties

Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...

Im Focus: Hydrogen Bonds Directly Detected for the First Time

For the first time, scientists have succeeded in studying the strength of hydrogen bonds in a single molecule using an atomic force microscope. Researchers from the University of Basel’s Swiss Nanoscience Institute network have reported the results in the journal Science Advances.

Hydrogen is the most common element in the universe and is an integral part of almost all organic compounds. Molecules and sections of macromolecules are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

Innovation 4.0: Shaping a humane fourth industrial revolution

17.05.2017 | Event News

Media accreditation opens for historic year at European Health Forum Gastein

16.05.2017 | Event News

 
Latest News

New approach to revolutionize the production of molecular hydrogen

22.05.2017 | Materials Sciences

Scientists enlist engineered protein to battle the MERS virus

22.05.2017 | Life Sciences

Experts explain origins of topographic relief on Earth, Mars and Titan

22.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>