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Genomics Key to Thermo's Life Tech Buy, but Implications for Proteomics, Multi-omics Work

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While Thermo Fisher Scientific's purchase of Life Technologies announced this week will no doubt have its greatest impact in the genomics and sequencing space, the deal has potential implications for proteomics, as well.

In particular, it raises questions regarding the future of Life Tech's proteomics research programs, and specifically its efforts to develop its Ion Torrent technology for protein detection (PM 7/13/2012).

The acquisition could also prove significant to growing efforts within the life sciences research community to integrate multiple omics disciplines, bringing, as it does, Life Tech's genomics platforms and expertise and Thermo Fisher's proteomics offerings under one roof.

As reported by GenomeWeb Daily News, Thermo Fisher will purchase Life Tech for $13.6 billion, paying $76 per share and assuming $2.2 billion of net debt. With the deal, Thermo Fisher enters the next-generation sequencing market, in which Life Tech is currently the number two player behind Illumina.

One of the key technologies Thermo Fisher will gain through the deal is Life Tech's Ion Torrent platform, which is based on ion sensitive field effect transistors, a technology that can detect biomolecules and binding events by monitoring changes in ion concentration.

Thus far, Life Tech has primarily used the Ion Torrent technology for nucleic acid sequencing. However, last summer the firm announced that it was accelerating development of the platform for proteomic applications (PM 7/13/2012).

Life Tech declined at the time to comment further on its plans for applying the technology to proteomics and did not offer information on precisely how it might be adapted for protein measurement. But the company did provide in the announcement a general outline of the principles underlying the detection of proteins on the platform that suggested an approach similar to its DNA sequencing efforts.

"Antibody/antigen complexes and proteins can be combined with bead-based sample-preparation technologies used on Ion Torrent's semiconductor sequencing technologies," the company said. "The sensitive signal detection available on the Ion Torrent's semiconductor chip works by recognizing electrical and ionic changes through a sensor, and the currently available products are being used with nucleic acids."

On a conference call this week following the announcement of the acquisition, Thermo Fisher CEO Marc Casper did not say whether efforts to develop the Ion Torrent technology for proteomics applications would be continued, though he did note that "there's some great innovation going on in Ion Torrent," and that the company was "excited about... that pipeline of innovation."

In an email to ProteoMonitor, Craig Smith, vice president of business development and R&D for Thermo Fisher's Bioscience division, said that the company had "not had an opportunity to fully explore the capabilities/feasibility of the [Ion Torrent] platform for non-genomics applications. This is something that we will be able to assess more fully as we go through the integration process."

"Clearly we would want to leverage the semiconductor-based ion sensor technology in new alternative high-value applications if it created value for our customers and it made business sense to do so," he added.

With its Orbitrap line of instruments, Thermo Fisher already owns one of the most widely used mass spec platforms in proteomics research. Field-effect transistor-based technologies like the Ion Torrent, however, could offer certain advantages compared to mass spectrometry – for instance, more compact size, lower costs, and high sensitivity. In addition to Life Tech, several academic facilities are researching FET-based systems as tools for proteomics, including the University of Copenhagen's Nano-Science Center and the University of California, Santa Barbara's Nanoelectronics Research Lab.

In addition to the potential proteomic applications of the Ion Torrent technology, Thermo Fisher acquires through the deal Life Tech's proximity ligation assay technology, a proteomics method that the company has licensed from Olink Bioscience.

Originally developed by the lab of Uppsala University researcher Ulf Landegren, the method could provide another point of entry into proteomics research for Life Tech's NGS tools. It uses pairs of antibodies attached to unique DNA sequences to capture proteins of interest which can then be read-out by detection of the attached DNA.

Currently, PLA approaches use real-time PCR to quantify the DNA amplicons formed when the target proteins are captured, but NGS offers potential advantages in terms of precision and multiplexing, Landegren told ProteoMonitor in a 2011 interview. In February 2011, as part of its European Ion Torrent Personal Genome Machine Sequencer Grants Program, Life Tech awarded Landegren an Ion Torrent sequencer to support his research into combining NGS with PLA.

Perhaps as significant as any particular technology platform is the opportunity the firms will have to combine Life Tech's genomics assets with Thermo Fisher's proteomics technologies into multi-omics workflows.

As evidenced by the work of numerous individual investigators as well as large-scale, high-profile efforts like the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (PM 9/21/2012), which is incorporating samples and data from the NCI's Cancer Genome Atlas project, and the Encyclopedia of DNA Elements project, which also includes proteomic analyses led by Boise State University researcher Morgan Giddings (PM 11/30/2012), scientists are growing more and more interested in integrating multiple omics disciplines.

In line with this trend, mass spec vendors have begun offering workflows and informatics packages to facilitate this sort of work. For instance, at last year's American Society for Mass Spectrometry's annual meeting, Agilent highlighted its recently released GeneSpring 12.0 software, noting a recent collaboration between the company and University of Washington researcher Mike MacCoss that combined GeneSpring with MacCoss' Skyline SRM-MS software to allow researchers to automatically generate SRM mass spec assays for target proteins identified via genomics studies (PM 5/25/2012).

With the Life Tech acquisition, Thermo Fisher would seem to have the technological assets in place to emerge as a leader in such multi-omics research.

"In principle, [Thermo Fischer] would be in a position to perform integrative analysis at a level no one else can," Stanford researcher Michael Snyder, whose lab has been at the forefront of such efforts, told ProteoMonitor. "Since more and more people are moving toward integrative analyses of the various omes, they are extremely well positioned and likely to be a very dominant force in this key area."

Thermo Fisher's Smith declined to speculate on any particular development efforts in this direction, but he noted the companies' offerings in their respective omics specialties, including Thermo Fisher's Proteome Discover software and Life Tech's Partek Genomics Suite, Avadis, and Ridom products.

"The value of full omics dataset integration, including proteome, genome, and metabolome into a single software package is something that will need to be more fully understood during the integration," he said.

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