Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Another look finds promising proteomics test is not biologically plausible

16.02.2005


In a new study, researchers present a "cautionary tale" about what may go wrong when using the fledgling science of proteomics to devise a diagnostic test for cancer.



In the February 16 issue of the Journal of the National Cancer Institute, researchers from The University of Texas M. D. Anderson Cancer Center detail why an experimental test intended to identify early ovarian cancer from a small sample of blood is unlikely to lead to a reliable clinical test right away.

After conducting repeated checks of the data that supported the test’s effectiveness, the researchers say their findings indicate that claims about the experimental protein-based assay are not biologically plausible. "We view this as a cautionary tale. If you are not careful with this new technology, whose quirks we don’t fully understand, you can find results that may be due to something other than biology," says the study’s lead author, Keith Baggerly, Ph.D., an associate professor in the Department of Biostatistics & Applied Mathematics.


He adds that this study "illustrates the need for researchers to set standards by which to conduct proteomics research," meaning that protocols involved in these investigations should be common across laboratories so that results from one lab can be verified by others. "We are moving in that direction," he adds. "The technology being used to develop a variety of proteomic diagnostic tests is getting better and we are getting more reproducible results."

Researchers worldwide are excited about the notion of using protein "barcodes" to identify individual cancers before symptoms appear, but Baggerly and others maintain that the promise of this emerging field of proteomics has not yet been met due to the difficulty in finding complex, reproducible patterns of proteins.

According to Baggerly, that now appears to be the case with the experimental ovarian cancer test at issue, which was first proposed in 2002 by researchers in the journal, Lancet. That study reported dramatic results using mass spectrometry to search for a pattern of proteins in blood. In several sets of blinded samples, the test detected all patients who had ovarian cancer and only misdiagnosed three healthy individuals.

But among others who subsequently tested the study’s data for reproducibility were Baggerly and his colleagues (Kevin Coombes, Ph.D., and Jeffrey Morris, Ph.D., from M. D. Anderson Cancer Center, and Sarah Edmonson, M.D., from Baylor College of Medicine). They say the issue centers on how the mass spectrometer data were analyzed.

A mass spectrometer is an instrument that can quantitatively measure the concentration of hundreds of proteins from a single sample. In short, it does this by using an electric current to propel ionized proteins toward a detector. The number of ions hitting the detector at each mass-to-charge ratio (also known as m/z ratio) is recorded to produce a protein spectrum. A peak in the graph of the spectrum represents a protein (the identity of which is often unknown).

The goal is to find a pattern of peaks that will distinguish between patients with cancer and those who are cancer-free. The authors of the Lancet study have reported different proteomic patterns in three separate data sets. Researchers at the State University of New York, Stony Brook, reanalyzed the data to look for reproducible patterns. In 2003, they reported finding a single pattern involving 18 peaks (or unidentified proteins) that could diagnose ovarian cancer across two of these data sets.

The M. D. Anderson researchers examined the quality of the data sets and concluded that this systematic protein pattern "is biologically implausible." Baggerly explains that discriminatory peaks appear to be spread across the entire m/z spectrum in the second data set, but "changes in protein expression associated with cancer should affect only a few specific peaks, not the entire spectrum."

Furthermore, the researchers say some of the protein peaks were found in regions of the spectra where, for technical reasons, mass spectrometry cannot be sampling proteins, and thus may be simply representing experimental "noise." Such results may come about from such procedural problems as incomplete randomization of samples, Baggerly says.

The study raises a question that is broader than the effectiveness of the experimental ovarian cancer test, the researchers say. "Are we going to be able to measure what we want to measure?" Baggerly asks. "Given issues in technology and a lack of standards, I think it will be a few years before we can know what works."

Nancy Jensen | EurekAlert!
Further information:
http://www.mdanderson.org

More articles from Studies and Analyses:

nachricht New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

nachricht Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Bare bones: Making bones transparent

27.04.2017 | Life Sciences

Study offers new theoretical approach to describing non-equilibrium phase transitions

27.04.2017 | Physics and Astronomy

From volcano's slope, NASA instrument looks sky high and to the future

27.04.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>