omation mbers - Society for Laboratory Automation and Screening

3:00 pm Tuesday, February 3 Clinical – Proteomics Room C1
Daniel W. Chan
Johns Hopkins University
600 N. Wolfe Street
Baltimore, Maryland 21287
dchan@jhmi.edu
Clinical Proteomics 2004
The future clinical diagnostics will be expected to provide more clinically useful information and cost less. Is
Proteomics the answer? In United States, one in four deaths is caused by cancer. Since cancer is a proteomic
disease, the study of cancer proteomics not only allow us to better understand the biology of cancer, but it
also provide us the opportunities to identify the dysfunctional protein as potential target for therapy and protein
biomarkers for cancer diagnostics. Since cancer is heterogeneous, it is unlikely that a single biomarker or protein
could be used to achieve its full clinical potentials, such as screening, detection, prediction or monitoring of
cancer therapy. Maximum clinical usefulness is likely to require a panel of biomarkers. New approaches to identify
biomarkers that could be used individually or in combination for cost-effective screening of diseases are urgently
needed. My presentation will focus on the use of surface-enhanced laser desorption-ionization (SELDI) protein
chips coupled with time-of-flight mass spectrometry (MALDI-TOF). Because large amounts of data are often
generated, the effective and appropriate use of bioinformatics tools become critical to analyze the expression data
and to avoid selecting biomarkers whose performances are influenced mostly by non-disease related artifacts in
the data.
In summary, the combination of proteomics and bioinformatics tools could facilitate the identification of proteins of
clinical interest. I will present some of our work at the Johns Hopkins Biomarker Discovery Center and the HUPO
plasma proteome initiative.
3:30 pm Tuesday, February 3 Clinical – Proteomics Room C1
Keith Ashman
MDS Sciex
71 Valley Drive
Concord, Ontario, L4K 4V8 Canada
keith.ashman@sciex.com
Combining LC and MALDI Mass Spectrometry: A Way to a Simpler Workflow?
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Co-Author(s)
Chris Lock
It will be shown that while the benefits of LC fractionation prior to MALDI analysis for even single protein digests
are evident, the real gains are made in the analysis of highly complex samples such as serum, containing dozens
of peptides from multiple proteins. Signal suppression and competition during the ionisation process will severely
limit the coverage obtainable if such samples undergo a single spot MALDI analysis. The benefits of separation
also extend to MS/MS analysis. Sample longevity is always a consideration when many MS/MS acquisitions
are required, but by spreading the peptides across many sample spots the number of obtainable MS/MS
spectra before all sample is consumed increases greatly.The decoupling of the MALDI ionisation process from
the TOF analyser in the o-MALDI 2 QSTAR XL mass spectrometer enables the instrument to demonstrate and
maintain superb mass accuracy and sensitivity in both MS and MS/MS modes of operation. Internal calibrants
are unnecessary and the sample surface morphology has no impact on instrument performance (an important
consideration in LC/ MALDI where the organic composition and hence morphology of each sample spot as it dries
will vary). This also allows a variety of sample preparation devices to be used. These benefits will be of signifcant
advantage as mass spectrometric techniques become more widely used in the search for and use of disease
markers for clinical diagnostics. Especially if the sample preparation methods are both simple and automated.