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spots over a tissue surface by laser irradiation and MS detection over a
500 Da to 80 kDa range and (ii) data analysis by color coding to indicate
the amount of sample detected (obtained by data integration of each
peak) [113]. Comparison of an optical image and MS image integrates
histopathological and biochemical features of the tissue sample for
better medical assessment. Further clustering of mass spectral data
could distinguish over different histological groups [114].
In a different strategy for profiling serum to identify ovarian cancer,
Petricoin et al. [115] used SELDI-TOF to identify potential biomarkers.
In SELDI (surface-enhanced laser desorption ionization) the MALDI
target is replaced by a chromatographic surface. Consequently, a subset
of proteins/peptides is fractionated on the target plate based on the
affinity for certain chemistries [116]. The initial high-throughput appeal
of this protein chip platform has been hampered by two important
issues: (i) analytical validation of the data and (ii) correct bioinformatics
analysis. Analytical validation of this platform was recently performed
by Zhou et al. [117] using a high-resolution TOF instrument. At the
same time, new methods for data analysis in SELDI-TOF are emerging
[118]. Thus, it appears that this technology will make a major impact in
this area of research.
A systems biology approach can be applied in the clinical setting.
Beside clinical evaluation of tissue specimens or body fluids, mass
spectrometry can serve as a hypothesis-free tool for proteomics plat-
forms, as we have seen in the above examples of systems biology
studies. For example, multiple analyses of a sample using different tech-
nologies can be integrated in a single database. A database infrastructure
for high-throughput description of a given tissue should organize
(i) clinical information on patients, (ii) data available in public domains
(for example, databases of microarray experiments) together with func-
tional annotation of gene products, and (iii) results from experiments.
Studies on nonfailing human hearts integrated in a relational database
transcriptomics and proteomics data with validated phosphoproteome
analysis, with mRNAs and proteins being extracted sequentially from
the same preparation [119]. Many more databases, similar to the one
described above, exist and are in the process of being developed.
Integrated databases are the templates in systems biology research for
comparative studies that aim for better diagnostic capabilities and
eventually to unravel the cause of disease.
CONCLUSION
Mass spectrometry holds the promise of transforming results of biolog-
ical experiments from qualitatively described models to quantitative
models, in the era of “sequencing the primordial soup” (a phrase coined
by Shabanowitz et al. [32]). A large-scale MS experiment performs
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