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Think Big: The UK 100,000 Genome Project

In late 2012 the 100,000 genome project was launched. UK Prime Minister David Cameron announced a new initiative led by the National Health Service to sequence the genomes of up to 100,000 people and to use their genomic information in treatment and studies of cancer and other diseases. The government set aside 100 million GBP for this project.

hiseq-x-tenGenomics England which is heading the project now named 10 firms that have been selected to for the assessment of the next phase of the project. The companies are Congenica; Diploid; NantOmics; Genomics Ltd.; Illumina; Qiagen; Lockheed Martin; NextCode Health; Omicia; and Personalis.

As part of the recently completed stage, Genomics England in February sent out a questionnaire to 28 participants in relation to 10 cancer/normal samples and 15 rare disease trio samples.

Illumina is partnering as well and will contribute with the ultra-high throughput sequencing platform HiSeq XTM Ten.

What will be the next step? Sequencing everyone?

PacBio launches new chemistry and software

In a press release Pacific Biosciences announced the latest enhancement for the PacBio RS II single molecule DNA sequencer. The latest release of the polymerase 6 and chemistry 4 (P6 – C4) version in combination with improved software enhances the performance and output of the platform by 45%. The average read length is now 10,000 – 15,000 bases and up to 40,000 bases for the longest reads. Depending on the nature of the DNA a single SMRT cell will deliver 500 million to 1 billion bases.

The new chemistry will replace the current P5 – C3 chemistry and is recommended for all SMRT sequencing applications.

This new release also includes improvements to the SMRT Analysis software suite for long amplicon analysis and the Iso-Seq™ method. Together with chemistry enhancements, these advances boost accuracy, speed up analysis, and support sequencing of multiplexed amplicons of different sizes.

Epigenetic study confirms: Tobacco addiction during pregnancy

Courtesy of FreeDigitalPhotos.netIn the morning paper I found a very interesting article from Kathrin Zinkant about smoking during pregnancy (Sueddeutsche Zeitung, Wissen, July 31 2014). It is long known that smoking during pregnancy is taboo. However, estimated 5% – 10% of pregnant women in Germany still smoke, many of them because they are not aware of the pregnancy in the first trimester. Tobacco toxins can harm significantly. Known consequences are reduced weight at birth, damaged lung function and unusual behavior.

In the world’s largest study of the consequences of smoking during the first trimester of pregnancy the DNA methylation status of almost 900 new born babies was studied and compared with the DNA methylation of babies whose mothers did not smoke. It could clearly be shown that the methylation status between the two groups differed. Methylation can alter the activity of genes up to complete silencing. There is evidence that such methylation patterns can be inherited to later generations.

Affected genes belong to known developmental genes and also genes that are involved in tobacco addiction. This confirms the suspicion that tobacco addiction may already be induced during pregnancy. Despite the fact that women should quit smoking before they become pregnant (or better do not smoke at all) it has also to be considered that second-hand smoking is a permanent danger for unborn, child and adult health.

First Oxford Nanopore MinIon data available: Is this the end of PacBio?

Nanopore SequencingResearchers from the University of Birmingham in the UK last week publicly released data they generated with Oxford Nanopore Technologies’ MinIon nanopore sequencer, the first group to do so since the company started its early access program this spring (see In Sequence report).

The sequence is derived from a Pseudomonas aeruginosa genome and is a single 8.5 kilobase read. It was posted by Nick Loman from the institute of Microbiology and Infection at the University of Birmingham. It was possible to identify the serotype O6. The sequence can be found here. It is of low quality with 71% identity of the spanned region.

Konrad Paszkiewicz, director of the Wellcome Trust Biomedical Informatics Hub and head of the sequencing service at Exeter, has been writing about the group’s experience on the Exeter Sequencing Service’s blog. “Even at this stage, this platform has the potential to steal large chunks out of the market from the likes of PacBio,” Paszkiewicz said.

We will have to wait for more data until we see how useful the technique will be and how the technique is able to compete against other Nanopore sequencers e.g. the device of Genia that was recently acquired by Roche.

Work where others make holidays !

Prof. Leonid Moroz from the University of Florida has become the first scientist to sequence the genome of fragile marine creatures on board a ship in real-time (see scientific computing world).

copaseticBecause of the difficulties of storing or shipping their genetic material, it has hitherto been difficult to sequence the genomes of marine species. However, researchers at the University of Florida have got round this problem by deploying a fully-equipped genomic laboratory aboard a ship called the Copasetic and sending the initial data via a satellite link to the University’s new HiPerGator supercomputer.

Aboard the Copasetic in early February and later in March-April, Professor Leonid Moroz, from the University of Florida, and his team where able to perform transcriptome sequencing of 22 organisms, among them rare comb jellies.

The first results of the sequencing at sea were presented at the international conference, Advances in Genome Biology and Technology, held at Marco Island, Florida in February.

Is China breaking the dominance of Illumina?

BIGIS-4 is the name of an independently developed next generation sequencer made in China. The sequencer shall challenge the dominance of Illumina. On 18 April, scientists from the Beijing Institute of Genomics (BIG) of the Chinese Academy of Sciences and partner company Zixin Pharmaceutical Industrial Co Ltd demonstrated their BIGIS-4 sequencing machine in Changchun, Jilin province.

The Chinese machine has a longer read length than dominant sequencers like those made by Illumina in the US. Its manufacturing cost will be one third cheaper than imported machines, and operation costs about one fifth lower, according to Yu Jun of BIG, chief scientist of the project. Yu was also a co-founder of Shenzhen-based BGI, a spin-off of BIG and now the world’s largest sequencing service provider.

Yu’s sequencer differs from Illumina’s in that the fluorescent tag is cleaved from the newly synthesised DNA as it is incorporated, so that the reading speed is much quicker. This is similar to the pyrosequencing technology employed by Roche Diagnostics’ subsidiary 454 Life Sciences.

A publication about the complete genome sequencing and assembly of a Glaciecola mesophila spec. with BIGIS-4 is published here.

The next step after sequencing: Synthesis of a designer chromosome

Next generation sequencing allows deciphering genomes of any kind and size; But, what to do with all this information?

Now a group of scientists from the John Hopkins University in Baltimore around Jef Boeke and 79 other authors published that they have been able to synthesize one of the 16 chromosomes of the baker’s yeast. Instead of the natural 317,000 bases they have reduced the chromosome to 274,000 bases by leaving out what they regarded as redundant or not necessary to grow under cell culture conditions.

Yeast cells already today produce important substances in large fermenters. They are used for bio fuel production but also for the production of Artemisinin, a potent malaria drug.

By reducing the genome of such organisms, the perfect “factory” can be designed in the future that delivers high yield of the desired substance at a minimum cost and a minimum contamination with other undesired metabolic byproducts. The White Biotechnology is certainly a hope for our permanent growing population. A number of companies engaged in this field can be found here.

Synthetic DNA – Data Storage For Eternity?

In the April issue of the journal Spektrum der Wissenschaft I found a very interesting article from Jan Dönges about data storage of information with the help of synthetic DNA (oligonucleotides). He describes the work of Ewan Birney and Nick Goldman from the European Bioinformatics Institute (EBI) in Hinxton, UK who have developed a strategy that allows coding data in strings of A, C, G and T nucleotides (Nature 494, 77-80, February 7 2013). They coded all sonnets of Shakespeare, a photo of the institute, the original paper of Watson and crick about the structure of DNA, an audio recording of the speech of Martin Luther King “I have a dream” and file with coding instructions; all together 739 kilobyte of information. They ordered the oligos and sequenced them on an Illumina HiSeq 2000. They received a text file of the letters A, C, G and T that could be converted into the original data. The complete code and sequence can be found here.

From sequencing experiments like the mammoth or the Neanderthal man we know that DNA is at least 10,000 years stable, longer than any other data storage. In addition it is extremely dense. With 1 gram of DNA it is possible to code more than 2 petabyte (1015 byte), or 2.3 million gigabyte. The volume of a coffee cup would be sufficient to code 100 million hours of high resolution videos. It is to be expected that the technology could even be improved in the future as long as mankind still is interested in DNA. The cost for the experiment was quite high compared to other storage media like tapes, HDD or DVDs. However, already after 600 years of making consecutive security copies of tapes the cost is compensated. So, if we want to conserve the knowledge of mankind for very long periods and make sure that it survives possible major disasters in the future, this seems to be a reasonable strategy

Sequencing Performance versus Marketing Performance

Recently, a number of groups have attempted to compare the two platforms PGM and MiSeq, including the Sanger Institute a group from the University of Birmingham, and BGI. None of these studies have conclusively named a winner, and each group comes to slightly different conclusions.

In a blog of Genome Web’s “The Daily Scan” the different findings in the three comparison studies are discussed heavily. On the one hand different chemistries or older versions are compared with newer ones, on the other hand different application require different technologies.

According to a report by Jon Groberg at Macquarie Equities Research, Groberg cites several factors leading to Life Tech’s better selling success of the PGM over Illumina’s MiSeq (1300 vs. 700 systems sold): price — the PGM sells for $75,000, while the MiSeq goes for $125,000; Life has a more extensive commercial reach; the trajectory of improvement for the PGM is greater than for the MiSeq; and the PGM excels at certain key applications.

Of note are the differences in sequencing cost, based on list prices (see Sanger Institute study). The MiSeq came out cheapest, at $502 per gigabase, followed by the PGM, at $1,000 per gigabase using the Ion 318 chip, and the PacBio, at $2,000 per gigabase. All three platforms produce data at a greater cost than the Illumina GAIIx, at $148 per gigabase, and the HiSeq 2000, at $41 per gigabase.

What is your experience with the two systems?

The Dark Side of Life

Recently the Hollywood filmmaker James Cameron (director of “Titanic”) reached in a custom made submarine the deepest point of the Mariana Trench, breaking a world record for the deepest solo dive. Deep-sea trenches have lured explorers for decades, tantalizing them with glimpses of an ecosystem shrouded in darkness.

Although Cameron’s journey to the abyss yielded little new scientific data, it whetted the public appetite for information about life in the otherworldly environments of deep-sea trenches.

An international group of marine scientists may soon provide a feast of such data, from the first major systematic study of a deep-sea trench. If all goes well the team will start exploring the South sea of New Zealand in a depth between 6.000 and 11.000 meters. A team around Timothy Shank from the Woods Hole Institution (WHI) inMassachusetts will systematically explore this complete unknown biotope with robots. An article about this program is published in the recent issue of Science.

New forms of life and deep insight into evolution are to be expected.

As a scuba diver I am excited to learn more about this fascinating biotope and I am sure that Next Generation sequencing technologies will significantly contribute to new chapters of the book of life.