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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.

Nanopore MinION to be tested and evaluated in Sweden

There are many researchers and service providers who are talking about the MinION from Nanopore on a regular basis. Great things are expected from this innovative sequencing technology.

As previously mentioned, Oxford Nanopore has shipped some MinIon devices to early access users to receive some more data. As one of the few laboratories in Scandinavia, the Department of Animal Breeding and Genetics at the Swedish University of Agricultural Sciences has been chosen to test one of the latest sequencing technologies from Oxford Nanopore. By the size of the sequencer it is possible to bring the sequencer in the field.

Previously the department has tested leading NGS technologies in research related to the genes involved in the immune system of horses. Now the Nanopore technology will be used, compared and evaluated against the existing well-proven sequencing technologies.

I guess it is just to wait and see what the MinION will bring, if it will come up to expectations or not.

Will Oxford Nanopore´s MinION hold its promises?

When I first heard of the Oxford Nanopore technology, it sounded rather exciting: The company proclaimed a new technology which enabled sequencing with extremely long read lengths of up to 100 kbp at a reasonable accuracy and in a very short time.

The technology is based on so-called “strand sequencing”. This technique involves a protein nanopore, in combination with a specific enzyme. This enzyme is designed to feed a single strand of DNA through the nanopore. The bases of the DNA strand are identified as they pass through the pore.

The sequencing systems are called “GridION” and “MinION”, with the GridION representing a high throughput system, and the MinION being a miniaturised system the size of a USB stick.

NewsFirst data for the GridION system have been presented in February 2012 at the AGBT conference. After that, there had been hardly any news from Oxford Nanopore for a long time. Then in November 2013, Oxford Nanopore announced an early access program for the MinION system on the ASHG meeting. They also gave demonstrations of the system to selected customers in the company´s labs. However, the company did not show any sequencing data yet. In February 2014, Oxford Nanopore has started to issue invitations to the early access program, and the first MinION systems should be shipped soon.

On the AGBT meeting in Feburary, the first MinION sequencing data, generated by Oxford Nanopore and analysed by David Jaffe from Broad Institute, Cambridge, have finally been presented.  However, the first results were rather disappointing: The average read length was way below the expectations. As reported by In Sequence, Jaffe told that the average read lengths were 5.4 kbp and 4.9 kbp for the two bacterial genomes analysed. The raw error rate of the data was not disclosed. However, Jaffe said that there were “long perfect stretches” and “blocks of errors”.  The data was not suitable for de novo assemblies from MinION data alone. In the end, the researchers used the sequences to create better assemblies from Illumina data.

On a Plant Genomics Meeting in Kuala Lumpur in the end of February, Oxford Nanopore Technologies presented more data. They claim that they could “easily obtain” 50 kbp reads. They had generated reads spanning the entire 48 kbp bacteriophage lambda genome. They also show data to underline that the read length distribution obtained by Nanopore sequencing is determined by the size distribution of the input DNA. Slides of the presentation can be viewed here.

Even if the first results are somewhat disappointing, I think this is still an interesting new technique. Like it was with the PacBio system, the technology may need more time to overcome its childhood diseases. The next few months will show if the technology can hold the high expectations that have been raised.

News From The World Of NGS

Pacific Bioscience’s instrument PacBio RS is known as the third generation sequencing technology. And again they proof their innovative character. During the course of the last couple of months two new chemistry packages have been released (XL & P4). And during the last couple of days two even more interesting news were spread:

1. Roche and PacBio’s signed an agreement for codeveloping diagnostic products for the PacBio RS instrument (Genome Web). From my point of view this is a huge signal. Roche, as an experienced player in the NGS market with its own sequencing instruments see’s a lot of potential in the SMRT technology. So the PacBio RS system obviously got out of the teething phase and will increase its importance in the NGS business in the coming months.

2. And also New England Biolabs a big player in the area of enzyme production, proteomics and drug discovery is using the PacBio RS to study bacterial methylomes and work on new reagents for 5-mc detection. And the CSO from NEB highlights that they have choosen “the PacBio system to study bacterial methylomes because of a unique feature of SMRT sequencing that enables the detection of base modifications through the system’s kinetics”. (Genome Web)

Beside the great news for Pacific Biosciences als Life Technologies or better Thermo Fisher signed a great deal with the Chinese Dx firm iGenomics to install 32 Ion Proton sequences in 2013 (Genome Web).

And clearly all developments focus on Molecular Diagnotics and Clinical Diagnostics. And to add the missing link in this news update also Illumina recently announced that they partner with G3 to identify novel biomarkers and pathways in cardiovascular disease.

Recently Launched Tools for Genomic Sequencing

Costs for DNA sequencing decreased tremendously the last years. New technologies and better methods cause that rapid drop in prices.
On the other hand, the field of sequencing is pushed forward with

  • methods to enrich nucleic acid samples,
  • kits that simplify library preparation from a variety of samples, and
  • services to assist the researcher with all aspects of sequencing.

Read more at the Nature Product Focus; the article was published in Nature 26 September 2013

Running a NGS Company Is Profitable

A recent article in GEN (Genetic Engineering & Biotechnolgy News) ranked the 2012 salaries of the TOP 20 CEO’s of life sciences tools and technologies providers.

Amongst them: the CEO’s of PacificBiosciences, Illumina, Life Technologies:

Michael W. Hunkapiller, Ph.D. (PacBio) $2,177,002

Jay T. Flatley (Illumina)  $8,171,080

Gregory T. Lucier (LifeTech) $10,268,445

But although this is really impressive, it’s still not outrageous. Imagine being a 28-year old soccer player: you can earn 4times as much as G.T. Lucier … (Forbes)

The complete article can be found here.

GENReport: NGS Trends In Cancer Research & Clinics

GENReport_Publication growth
Enal Razvi, Ph.D. from SelectBio U.S. summarised very nicely the trends of next generation sequencing in cancer research and cancer diagnostics for Genetic Engineering & Biotechnology News.

Visit the GEN website to download the complete PDF report.

Do You Still Remember Which NGS Sequencer Was The First On The Market?

gs-20It was 2005, when Roche launched the first NGS sequencer called the Genome Sequencer 20 (GS 20). This device was able to achieve read length of approx. 100 bp, with a total data output of approx. 20 Mbp per run.
As a consequence, sequencing of a bacterial genome of 5 Mbp (e.g. E. coli) with 20-fold coverage required 5 individual runs on the GS 20. Sequencing costs were in the range of several tens of thousands Euros, bringing the cost compared to Sanger sequencing down 10-fold.

Looking back it’s also difficult to imagine for me, that the GS 20 software at that time could handle genomes of a max size of 50 Mbp only.

Since then, 5 major leaps in the Roche/454 sequencer’s development took place:

  • GS 20 to GS FLX
  • GS FLX to GS FLX with Titanium chemistry
  • Launch of the desktop sequencer GS Junior
  • GS FLX Titanium to FLX+
  • FLX + to FLX++ sequencing (new GS FLX software v2.8)

This all happened in only 7 years.

The current Roche/454 FLX++ chemistry enables read length up to 1100 bp and read outputs of up to 1.2 Gbp per run. As a consequence, today, 8 years later, sequencing of a 5 Mbp bacterial strain can be done on a ¼ plate of a full run. The 9-10-fold longer reads make a great difference in respect to contig length and contig number of the genome assembly.

Meanwhile other NGS sequencers dominate the market. Nevertheless the Roche /454 technology is still of superior quality for de-novo sequencing of genomes of any size and for amplicon sequencing.

Acquisitions And Rumours

The last time I wrote about acquisitions is a while ago. But that does not mean that nothing happened – yet the opposite is the case: the NGS business is so dynamic that I am not sure which news are already outdated one day later.

But now it might be time to have all news comprised in this blog to at least list the lastest mergers, acquistions and rumours in the field of NGS:

 

1. QIAGEN acquired Ingenuity for $105M

QIAGEN one of the market leaders in Sample & Assay Technologies now builds up a branch in Next Generation Sequencing. The 1st step was the acquisition of Intelligent Bio-Systems in 2012. The expected launch of the upcoming sequencing device is scheduled for mid 2013. The acquisition of Ingenuity now seems to be last piece of the jigsaw for a complete NGS workflow from sample preparation to complete data analysis (see PR QIAGEN). From my point of view I am really confident regarding the sample preparation and the data analysis. But some doubts remain in respect to the NGS device – at least I have never heard about it before….

1. Life Tech – in great demand

Just two days ago an article in GenomeWeb revealed that two other bidders for Life Tech were Roche and Sigma-Aldrich. The rumours I heard so far only said, that Roche was interested in IonTorrent to push their own NGS business. According to the respective GenomeWeb article the Thermo – Life deal is anticipated to be completed in early 2014.

3. Roche – expanding or downsizing?

But although some rumours say that Roche is still interested in IonTorrent it might also be that they will shift their focus. Especially since Roche has downsized their effort in Applied Science business. According to the announcement Roche will integrate these products with other units and they also stopped the collaboration with DNAe to develop a semiconductor sequencing platform. Maybe because a new development might take too long. Maybe because the deal for IonTorrent is under way…

And while writing the summary I remembered again why these updates are so difficult to phrase: I don’t get rid of the feeling that something new, something more interesting is already close to publication.

AROS AB – now a member of the Eurofins group

AROS Applied Biotechnology A/S
With today’s press release I am happy to announce that AROS Applied Biotechnolgy A/S  is now a member of the Eurofins group.

Here is a short introduction of our new colleagues from AROS:

  • AROS was founded in the year 2000
  • AROS started as a spin off of from the Aarhus University Hospital and was the first service provider for Affymetrix in Europe
  • AROS is based in Denmark and provides a long term experience in sample preparation, microarray analysis and next generation sequencing (NGS)
  • Nowadays AROS has a leading position in NGS service for pharmaceutical research
  • AROS is an Illumina reference lab for next generation sequencing
  • The main focus in NGS is RNA-Seq and exome sequencing that is accomplished with the exome designs of the leading provider in this area (Illumina TruSeq Exome Enrichment, NimbleGen EZ Capture & Agilent SureSelect)

“AROS is an excellent fit […] with our focus on high-quality next-generation sequencing […]” (Dr. Gilles Martin) and therefore I am confident that this new alliance will help us both in further expanding our experience level in NGS and to benefit from our complementary strength.

I am sure you will hear more about the activities from AROS on our blog and hope you join me in welcoming AROS as a member of Eurofins.