NEW YORK (GenomeWeb) – With their collaboration announced last week, Waters, Imperial College of London, and BGI are aiming to further the integration and clinical translation of genomic and metabolomic information.
According to Rob Plumb, director of metabolic profiling at Waters and a visiting professor at Imperial College, the collaboration will tackle development of technology and methods for linking and delivering genomic and metabolomic information with an initial clinical focus on rare diseases.
The agreement would also seem from Waters' perspective a chance to solidify its foothold as a mass spec supplier to BGI. Perhaps the world's biggest player in genomic sequencing services, BGI is also active in mass spec-based research areas like proteomics and metabolomics and will purchase new Waters mass specs, including the company's Xevo G2-XS QTOF and Xevo TQS tandem quadrupole instruments, as part of the collaboration, Plumb told ProteoMonitor.
From a research perspective, the three parties hope to pool their respective expertise and combine genomic and metabolomic measurements for use in prognostic, diagnostic, and monitoring applications, he said.
These two forms of omics data are particularly well suited to translational research, Plumb noted, in that they currently fit into time scales suitable for clinical applications.
"You can do metabolic phenotyping in a few minutes, and you can do genomics in a few hours," he said. "And that makes these two approaches suitable for being deployed in a clinical setting."
Plumb suggested two general approaches the collaborators will take toward combining genomics and metabolomics in meaningful ways. In the first instance, he said, they will use metabolomic measurements to confirm well-established genomic hypotheses.
"For instance, if you have a particular gene that has been changed or mutated or knocked out, then you should see a change in a particular pathway, which you should be able to target [through] a metabolic analysis which would look for an upregulation or a down regulation of the metabolites produced by or consumed by that pathway," he said, noting that such a targeted approach would typically be most applicable to "diseases that are heavily genetically based and are well understood."
The second tack is more discovery-based, performing broad analyses of genomic and metabolomic data to look for covariations between the two that appear linked to a particular disease state.
Also key will be bringing into the process metagenomic analyses of patient microbiomes, Plumb said. "One of the things that is very important when we look at this whole process is not only your genes but the genes of your gut microflora. [Because] a lot of metabolic processes are symbiotic with the microbial genome."
Perhaps the most important part of the collaboration, though, will be "to create a platform of bioinformatics tools that will allow the medical community to visualize the connectivity between the genomic and metabolic phenotyping data in a framework which they understand," he said.
Clinicians don't need simply a presentation of a patient's genomic and metabolomic data, he noted. "They need something to help them understand what treatment to deliver, and that is the step we need to take."
While Waters has in-house a variety of informatics tools, including software aimed at metabolomics research, the company aims to develop through the Imperial College-BGI collaboration "a commercially viable toolkit – something that is validated and supported that people can use globally," Plumb said.
The collaboration – particularly on the Waters-Imperial College end of things – also aims to develop methods for performing metabolomic work on smaller samples, which, he said, could enable researchers and clinicians to extend their analyses to samples collected remotely.
The collaboration will use a combination of Waters' QTOF instruments for the discovery-based metabolomic work and tandem quadrupole instruments for the more targeted analyses, Plumb said. Both, he added, will be attached to the company's Acquity UPLC systems.
Down the road, the collaboration could also expand to include DESI- and MALDI-based mass spec imaging, Plumb said. "As the collaboration progresses we will be looking at using that technology to generate mass spectral visualization of [samples] and put that together with genomics information [gathered] through tissue biopsies."
Waters has been a major supplier of mass spec technology in support of the metabolic phenotypic work of Imperial College researcher Jeremy Nicholson, one of the leaders of the recently announced collaboration. For instance, the company is the main supplier of mass specs to the Nicholson-led National Phenome Centre, a joint venture between Imperial College and King's College London launched in 2012 that specializes in translational metabolomic research.
Waters will also supply BGI with mass specs for the new project. This will enable all three collaborations to work on the same platforms, allowing for easy transfer of methodologies and capabilities, Plumb said.
BGI "already has some Waters mass specs and they are in the process of getting more of our instrumentation," he noted.
In a 2011 interview, Siqi Liu, associate director and head of BGI's proteomics division, told ProteoMonitor that the institute was looking to add as many as 50 new mass spectrometers over the next several years. Last year, Liang Lin, deputy head of proteomics at BGI-Shenzhen, told ProteoMonitor that the company had purchased five new instruments over the previous year, including a Thermo Fisher Scientific Q Exactive, an AB Sciex TripleTOF 5600+, and several triple quadrupole machines.
"Over the last three years, mass spectrometry has developed very quickly, and we are keeping close collaborative relationships with mass spectrometry companies such as Thermo Fisher, AB Sciex, Waters, and Bruker," he said at the time.
The collaboration is currently open ended, Plumb said, noting that Waters typically enters such agreements in three-year installments, evaluating after each installment whether to continue. Ownership of intellectual property generated by the collaboration will be determined on a project-by-project basis, he said, determined primarily by who provided funding for a given effort.