Diagnostics & Imaging Week

ORLANDO — Judging by the standing-room-only crowd at a session on new diagnostic frontiers in proteomics and metabolomics during the joint International Federation of Clinical Chemistry (IFCC; Milan, Italy)/American Association for Clinical Chemistry (AACC; Washington) annual meeting and clinical lab expo here, many are eager to learn how this technology is changing and will continue to change clinical applications.

During the session at the Orange County Convention Center, moderator Glen Hortin, MD, PhD, of the Department of Laboratory Medicine at the National Institutes of He-alth (NIH: Bethesda, Maryland), reminded his audience that the term "proteomics" was coined only in 1994, although the science behind it has been discussed for many years.

Leigh Anderson, PhD, founder and CEO of the Plasma Proteome Institute (Washington), described by Hortin as one of the founders of proteomics, told listeners that plasma is "the largest and deepest representation of the human proteome in one sample" and that it is in communication with essentially all tissues.

"A small number of proteins make up the top 99% of plasma by mass," Anderson said, noting that proteins measured clinically in plasma span greater than 10 orders of magnitude in abundance.

"Tissues leak proteins," he said, adding that any human protein may be detectable in plasma at some level.

According to Anderson, there probably are 90,000 forms of proteins secreted to function in plasma, although most are glycoproteins. Also, he said that there is a "wide spectrum" of proteins in plasma that are controlled by genotype.

The "dark side" of that, he said, is that the number of FDA-approved diagnostic protein tests "has been declining in the last decade, which is actually counterintuitive."

"It's possible that we've already found the really great diagnostic proteins," Anderson said.

He said no "diagnostic pipeline exists the way it does" in the pharmaceutical industry, which strives to keep a pipeline of drugs that will one day be ready to hit the market, with any luck as blockbusters.

In fact, he said, in diagnostics, most of the work on proteins is done in academic research centers, something he jokingly said may be because diagnostic testing doesn't offer the same levels of pay as does the pharmaceutical industry.

But Anderson said he continues to believe that there is the potential for finding diagnostic tests in other proteins. "We would like to be able to peel the onion" and dig down to find more proteins that could result in tests, he said, naming antibody affinity subtraction as a "starting point."

Based on the technologies that exist today to find more biomarkers, he said, proteomics has become an "elaborate" and "difficult" business. Technology alternatives for finding target proteins will be "explored aggressively" in the near future, he added.

In the afternoon session of the program, Saeed Jortani, PhD, of the University of Louisville (Louisville, Kentucky) offered insights from his pediatric studies funded by the NIH in his quest to find a protein test for children who suffer from obstructive sleep apnea, a condition that is just starting to be more widely discussed in adults, much less pediatrics.

However, Jortani told the audience that he had been "amazed at the magnitude of the problem" in children. As in adults, it is caused when normal ventilation is disrupted during sleep, and a patient could wake many times during the night and even suffer hypoxia.

In children with sleep-disordered breathing, the risks include behavioral and mood problems, learning deficits, cardiovascular morbidity and a decreased attention span, he said.

Obstructive sleep apnea (OSA) differs from what is known as habitual snoring, because that condition does not involve disruption of ventilation. But Jortani said it has been proven that there are "genetic reasons for OSA," adding that a non-invasive test, such as a urine test if the proteins could be identified, would be "of great benefit" to children and their families.

The standard test for OSA now used now involves having children spend the night in a sleep lab at a hospital with a parent, something that can cost as much as $2,000. Also, there often are very long wait times to be able to undergo this test, which is called a poly- somnograph.

The risk factors for pediatric OSA are passive smoke and asthma.

The hypothesis for the study that is being done is that OSA and habitual snoring in children will be associated with different urinary proteomic profiles, Jortani said.

He said that a good biomarker is an "early one," or one that can detect disease early in the process.

The study on which he is working has not been published, so he could not give more details. However, he said the study would be published in time for a proteomics conference to be sponsored by AACC in Washington this fall.

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