Delving into deep proteome: Ciphergen’s service strives to be “PCR of proteins”

At the recent ASMS Conference on Mass Spectrometry, held in San Antonio, Texas, Ciphergen Biosystems introduced the new Deep Proteome Research Services that bring the company’s Equalizer technology to biomarker discovery and identification.

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FREMONT, Calif.–At the recent ASMS Conference on Mass Spectrometry, held in San Antonio, Texas, Ciphergen Biosystems introduced the new Deep Proteome Research Services that bring the company's Equalizer technology to biomarker discovery and identification. Initially, working through its biomarker discovery service centers scattered around the world, Ciphergen will preferentially offer the new services to its existing customer base, which is familiar with its technologies, but also open it up to other interested parties.
"The services are really to provide use of the Equalizer technology to enrich samples for low-abundance proteins," says Ciphergen CEO, Dr. William "Bill" Rich. "We will also offer different levels of protein profiling services and higher levels of collaboration on projects that will utilize the Equalizer technology."
In the initial phases of Deep Proteome implementation, scientists in pharmaceutical or biotechnology companies – Ciph-ergen's primary targets – will bring or send their samples to the biomarker centers for enrichment, but eventually he expects the technology to spread to other facilities.
"We believe that this technology will become a very powerful incentive for people interested in doing biomarker discovery through our collaborative services on a higher level," he adds.
Ciphergen's new technology addresses the "dynamic range problem" that has long been a problem in proteomics research, whereby many of the most biologically interesting proteins in a sample are the lowest in abundance. In some samples, the difference between the most abundant and rarest proteins can be 104- to 106-fold.
Standard solutions to this problem rely on selective depletion of highly abundant proteins, but this can lead to overall protein loss (both high- and low-abundance) and the methods are generally low-throughput, multistep, and labor-intensive.
Ciphergen's Equalizer technology relies on protein affinity to a combinatorial peptide library attached to resin beads that are selective for upward of 106 to 107 proteins in a sample. Thus, when the beads are added to a sample, high- and low-abundance proteins are bound in roughly equal amounts and the excess material is washed away. The bound proteins can then be eluted for further analysis.
According to Rich, Ciphergen has seen a 104-fold improvement in the dynamic range using this method.
"What's nice about it is that it's a very straightforward process," he explains. "It takes a couple of hours, can use 96-well plates, and can be put into a high-throughput mode."
Rich sees the services providing advantages for drug discovery. Equalizer offers  scientists, who are "loaded with ideas from all the gene data about what target proteins may be interesting," a mechanism for performing hypothesis-driven experiments. Similarly, he says: "The clinic people like the de novo protein search because we can rapidly get differences [between healthy and disease samples] that translate into a nice assay with high predictivity to stratify patients."
"The beautiful thing about the Equalizer technology is it's the closest thing we've seen to what has been the hope of all the proteomics people, which is to find a 'PCR of proteins'," he adds. "That is, a way to get the signal-to-noise up, in this case, by reducing the noise instead of increasing the signal, as with PCR. Once you resolve that signal-to-noise issue-the dynamic range issue-in different fluids, without losing proteins, your downstream processes become far more powerful, whatever they are."
Ultimately, as he explains it, this will be necessary if scientists are to ever have any hope of probing the deep proteome.

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