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To Validate Biomarkers, Anderson Likes MRM Assays

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Mass spec-based MRM assays may serve as a good intermediate step to push proteomic biomarkers beyond the discovery phase and into the validation phase, according to Leigh Anderson, who gave the opening keynote lecture at the Association of Biomolecular Resource Facilities conference.

“We need to do really interesting things in discovery, but if we don’t do the validation, [the discovery] might as well not have been done,” said Anderson, who is the founder and CEO of the Washington, DC-based Plasma Proteome Institute.

A multiple reaction monitoring, or MRM, assay is a triple quadrupole mass spec-based technique that enables researchers to simultaneously and quantitatively measure a number of proteins of interest. In a paper published in the December 2005 Molecular & Cellular Proteomics, Anderson and a collaborator at Applied Biosystems showed that about 50 proteins could be monitored at the same time using an MRM assay.

In his ABRF presentation, Anderson noted that while the number of potential biomarkers being discovered is increasing steadily, there are only a handful of proteins that are interesting to measure clinically, and none of those has been discovered through proteomics.

One reason for this is that “we don’t have a pipeline for moving from biomarker discovery to a standard clinical test,” Anderson said. “Nobody funds biomarker validation. The National Institutes of Health funds biomarker discovery, but not validation.”

Immunoassay-based validation approaches, such as antibody arrays and ELISA tests, are relatively easy to perform, but they are expensive and may take a long time to develop, especially if antibodies for the candidate biomarkers are not immediately available, said Anderson.

As an alternative, Anderson proposed using MRM assays, especially for whittling down the number of candidate biomarkers from many tens to a panel of about 10 biomarkers, which would be reasonable to deal with during validation.

—Tien-Shun Lee


PATENT WATCH

US Patent 7,002,146. Ion sampling for APPI mass spectrometry. Inventors: Steven Fischer, Darrell Gourley, Patricia Cormia, James Bertsch, and Karl Hanold. Assignee: Agilent Technologies. Issued: February 21, 2006.

This patent covers an atmospheric pressure ion source that can be used with a mass spec. It produces ions by atmospheric pressure photoionization. According to the abstract, “it includes a vaporizer, a photon source for photoionizing vapor molecules upon exit from the vaporizer, a passageway for transporting ions to, for example, a mass spectrometer system, and a means for directing the ions into the passageway.”


US Patent 6,995,363. Reduction of matrix interference for MALDI mass spectrometry analysis. Inventors: Michael Donegan, Andrew Tomlinson, Perumanath Nair, and Peter Juhasz. Assignees: Applera and MDS. Issued: February 7, 2006.

This covers a “MALDI plate suitable for MS or MS-MS analysis provided with a composite coating that comprises a hydrophobic coating and a thin layer coating of a mixture of a MALDI matrix material and an intercalating agent such as a polymer.”


Datapoint

$16 million

Cash amount for which Varian acquired FTMS firm IonSpec. Additional payments could be made if FTMS-based products hit certain financial targets in a three-year period.


SHORTREADS

Bio-Rad acquired ProteOptics, an Israel-based maker of surface plasmon resonance technology. The firm’s technology, which uses image analysis to track optical changes without the need of molecular labeling to monitor biomolecular interactions, is anticipated to expand Bio-Rad’s proteomics offering.

Qiagen will bundle its sample preparation consumables with ActiveSight’s CrystalScan protein-crystallization screening service.

LifeSpan BioSciences sold most of its antibody catalog to Medical and Biological Laboratories International, a Massachusetts-based subsidiary of Japanese firm MBL. LifeSpan sold 921 antibodies to approximately 400 different protein targets, including 800 GPCR antibodies.

Waters will pay Agilent a one-time payment of £3.5 million as part of a settlement agreement to resolve a patent-infringement suit involving high-performance liquid chromatography technology.

Beckman Coulter reported its fourth-quarter 2005 numbers, revealing that while consumable sales were up 12 percent, overall income for the period declined 70 percent from the same period the previous year.

Waters and Thermo Electron will integrate the Waters Acquity Ultra Performance Liquid Chromatography system with Thermo’s line of mass spectrometers.

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