Proteomic Mass Spectrometry I: Ovarian Cancer and Experimental Design

Keith Baggerly
Department of Biostatistics & Applied Mathematics
M.D. Anderson Cancer Center

Abstract:

Just as microarrays allow us to measure the relative RNA expression
levels of thousands of genes at once, mass spectrometry profiles
can provide quick summaries of the expression levels of hundreds
of proteins. Using spectra derived from easily available 
biological samples such as serum, we hope to identify proteins 
linked with a difference of interest such as the presence
or absence of cancer. With respect to ovarian cancer, this
approach has been claimed to provide diagnostic tests with
near perfect sensitivity and specificity (Petricoin et al. 2002).
Based on the strength of these results, a home-brew test known
as OvaCheck has been announced for 2004. 

In this talk, we will briefly introduce the mechanics underlying
the mass spectrometry variant known as surface-enhanced 
laser desorption and ionization/time of flight (SELDI-TOF). 
We then take a pictorial tour through the raw data, looking
for interesting structure both in a single experiment and 
over multiple experiments. Unfortunately, what the data
most clearly shows is not biological structure, but rather
the need for careful experimental design to ensure that the 
structure found is not due to systematic bias. Some more recent 
objections to our results will also be discussed.