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Study Shows Reproducible SELDI-TOF-MS Analysis

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Chipping away at the theory that protein peaks are not reproducible from instrument to instrument, a new study by six of the National Cancer Institute’s Early Detection Research Network centers showed that SELDI-TOF-MS analysis of 28 prostate cancer and control samples produced reproducible results.

In the study, published in Clinical Chemistry, 28 blinded samples, including 14 prostate cancer samples and 14 control samples, were analyzed by each of the participating institutions. They used filters and signal processing algorithms developed by researchers in lead author John Semmes’ laboratory at the Eastern Virginia Medical School’s Virginia Prostate Center.

Results showed that researchers from all six sites correctly identified the 28 blinded samples. Though the data do not prove that a diagnostic based on the technology is reproducible, they may bring mass specs one step closer to the world of clinical diagnostics.

“This was a validation of instrument reproducibility and portability,” says Semmes. “The take-home message is that inter-lab reproducibility is equal to intra-lab reproducibility. People were telling us that peaks found at one place were not reproducible at another place. That’s just not true.”

Stephen Naylor, an adjunct professor of genetics and genomics at Boston University School of Medicine, says the researchers should be applauded for making the effort to look at inter-lab reproducibity. However, the study is not very significant in terms of finding biological markers that are relevant to prostate cancer, he adds.

To validate the profile, Semmes’ research group is spearheading a study involving 1,200 samples from eight institutions. The researchers seek to prove that the profile of peaks found is specific and sensitive for prostate cancer.

— Tien-Shun Lee

PATENT WATCH

US Patent No. 6,835,927. Mass spectrometric quantification of chemical mixture components. Inventors: Christopher Becker, Curtis Hastings, Scott Norton. Assignee: Surromed. Issued: December 28, 2004.

The patent describes a method for obtaining relative quantitative information about components of chemical or biological samples by normalizing mass to yield peak intensity values that accurately reflect concentrations of the responsible species. A normalization factor is computed from peak intensities of those inherent components whose concentration remains constant across a series of samples. The methods are particularly useful for differential phenotyping in proteomics and metabolomics research, in which molecules varying in concentration across samples are identified.

 

US Patent No. 6,829,539. Methods for quantification and de novo polypeptide sequencing by mass spectrometry. Inventors: David Goodlett, Andrew Keller. Assignee: Institute for Systems Biology. Issued: December 7, 2004.

The invention provides a method of determining an amino acid sequence of a parent polypeptide. Among other steps, the method includes: (a) obtaining mass spectra of two or more differentially labeled polypeptide fragments of a parent polypeptide and (b) assigning a mass and a weighting characteristic to two or more paired signals having a difference in mass corresponding to an integer value of said differential label, the weighting characteristic combining properties of each signal within said paired signals.

 

Datapoint

9

Estimated number of times a shotgun experiment has to be repeated to identify all proteins in a sample, according to John Yates of the Scripps Research Institute at an NIH workshop

 

Over the next three years, Qiagen and the Australian Proteome Analysis Facility plan to co-develop new proteomic sample preparation tools designed to reduce the complexity of samples prior to analyzing the proteins.

 

The Searle Funds have awarded $1.5 million to the Chicago Biomedical Consortium for a proteomics/bioinformatics demonstration project designed to join “experimentalists, instrumentalists, and informaticians to apply new technology and new analytical techniques to addressing the basic questions of proteomics.”

 

NextGen Sciences has licensed a new protein production technology from Oxford Brookes University and is making it commercially available. The technology, called FlashBAC, speeds up the production of recombinant proteins in insect cells by eliminating the need to separate recombinant baculoviruses from parental viruses.

 

By agreement, Celera Genomics and Seattle Genetics will explore a number of cell surface proteins discovered by Celera’s proteomics group as antibody targets.

 

Silicon Graphics has installed an Altix 3000 supercomputer, an SGI SAN solution, and an SGI InfiniteStorage Shared Filesystem CXFS for use with the China Human Proteome Organization’s Human Liver Proteome Project, which is funded with $16 million from the Chinese government for a three-year pilot study to be completed this year.

 

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