Next Generation Sequencing

A lot of people are looking into buying a next generation sequencer these days and weighing the pros and cons. People are obviously attracted to the idea of expanding their research capacities with high throughput sequencing but at the same time they are worried about the skills and resources needed to run the instruments. As a company we are trying to bring out solutions that alleviate the bioinformatics obstacles in the process.

Genome Technology have recently posted an article which discusses some of the challenges facing the purchasers of NGS instruments.

Boston, USA — April 29, 2008 — Today at the Bio-IT World Conference & Expo in Boston, USA, CLC bio announced collaboration with Microsoft Corp. on integrating CLC bio’s extensive bioinformatics solutions with Microsoft’s software platform, for the benefit of companies, corporations, and institutions in the biotech, pharmaceutical, and life science sectors. CLC bio has already added support for Microsoft SQL Server in its database solution, CLC Bioinformatics Database, as well as support for Microsoft’s high-performance computing solutions, Windows Compute Cluster Server 2003 and Windows HPC Server 2008.

Dr. Rudy Potenzone, worldwide pharmaceutical industry technology strategist at Microsoft Corp. and director of the Bio IT Alliance, states

We are delighted to work together with CLC bio, a member of the Bio IT Alliance and one of the world’s leading bioinformatics solution providers. This collaboration will ultimately help life sciences firms transition to the Microsoft platform throughout their research and development departments. CLC bio’s tools, fully integrated with the Microsoft Office System, increase ease of use and expand the number of potential users, while reducing administrative overhead and creating a lean workflow. Furthermore, CLC bio’s internationally renowned experts are available for consulting and customized development.

Jan Lomholdt, Vice President at CLC bio, continues

With our support for Microsoft’s server solutions, the first step in the process has already been taken. The second step is to further advance our collaboration in areas such as Next Generation Sequencing and high-performance computing, which ultimately can help realize the potential of personalized medicine. As a former member of Microsoft’s World Wide Advisory Council, I have first hand experience of the strength and potential Microsoft brings to the table with a collaboration like this, which of course is interesting for a company like ours.

Windows HPC Server 2008, the successor to Windows Compute Cluster Server 2003, includes a common set of High Performance Computing productivity tools that reaches across desktop and clusters, including a new Parallel Computing Initiative for multicore development. CLC bio’s high-performance computing solution for servers and clusters, CLC Bioinformatics Cell, supports Microsoft’s Message Passing Interface (MPI) in order to run bioinformatics algorithms such as HMMER, ClustalW, and Smith-Waterman on Windows HPC Server 2008 installations.

All CLC bio’s solutions are cross-platform, running on Windows 2000, Windows XP, Windows Vista, as well as Mac OS X and Linux.

Researchers from Helicos and the universities of Stanford and Ohio have published a genome re-sequencing proof-of-concept paper in the journal Science. The team reports a 100 percent coverage of the 6,407 nucleotide genome which was sequenced with more than 150-fold coverage. Read lengths averaged about 23 bases. A point of interest is that the error rate of the sequencing was quite high, especially in homopolymer regions. However, Helicos reports that a new generation of nucleotides has since been developed that give more accurate homopolymer sequencing, and lower overall error rates. GenomeWeb has more. I have to go get hold of the original paper and read it before I blog on.

Here is the original press release.

NimbleGen are now offering their high-density oligonucleotide microarrays as a programmable genomic selection technology to allow targeted sequencing of genomic regions such as e.g. exons.

NGS technologies are based on random amplification of input DNA. This makes sample preparation easier but leaves the actual sequencing undirected. The idea of capture arrays is to insert a selection step prior to the actual sequencing. The array is programmed to capture only the genomic regions of interest and thus enable users to utilize the full capacity of the NGS machines in the sequencing of specific genomic regions of interest.

Image from the NimbleGen website, illustrating the array capture process.

Applied Biosystems have released data to the public from the genome sequencing of a Yoruba Nigerian HapMap sample. In their press release, AB claim that the data were generated using only 7 runs of the SOLiD system and at a total sequencing costs of less than 60.000$.

The data covered the genome 12 fold and paired end information provided a physical coverage of a 100 fold, i.e. the coverage stemming from the inserted but not sequenced part of paired end reads. Millions of SNP’s and a large number of structural variations were identified from the data.

As an amusing aside, AB gave these funny facts about the dataset:

• If all 36 billion bases were spread out at 1 millimeter apart, they would extend 36,000 kilometers, or more than 4,000 times the height of Mt. Everest, which at 8,848 meters above sea level, is the highest mountain on Earth.
• If all 36 billion bases were spread along the Great Wall of China at 1 millimeter apart, this would equate to spanning the 5,000 kilometer wall more than 7 times.
• If a person were to proofread the 36 billion bases in this dataset at one letter per second for 24 hours-per-day, it would take 1,200 years to read the entire data set.
• If each base represented one individual in the world population, the dataset would account for more than 5 times the entire world population of 6.8 billion people.
• This dataset, at 36 billion bases of DNA sequence, is equivalent to 360 times all of the 100 million visible stars in the Earth’s galaxy.