PROTEIN NETWORKS - Complex Systems Science in Biomedicine - page 251

Gray (9) synthesized results from a series of studies that identify a likely cause
using a protein expression analysis approach. Two-dimensional protein electro-
phoresis in rats showed that application of cyclosporin A inhibits the expression
of the protein calbindin-D in rat kidneys. This response is associated with in-
creased calcium excretion and calcium accumulation in the kidney. Calbindin 28
has been implicated in calcium transport and calcium buffering, thus making it a
prime candidate for mediating this side effect.

4.4. Diagnosis

One among a growing number of proof-of-principle studies for diagnostic
applications is that by Gordon and collaborators (cited in (21)), which describes
the use of gene expression analysis to distinguish two types of lung tumors: ma-
lignant pleural mesothelioma (MPM) and adenocarcinoma (ADCA). Accurate
differential diagnosis is critical in case of these two tumors, as treatment strate-
gies differ greatly for them. However, diagnosis is difficult using conventional
methods. Using large-scale gene expression analysis, the authors identified eight
genes that changed their expression level most drastically in a "training" set of
16 ADCA and 16 MPM tissue samples. Using these biomarker genes as diag-
nostic indicators, the authors were able to diagnose 99% of presented tumor
samples as being either ADCA or MPM (21).
The above examples are hand selected from a growing literature in this area.
They illustrate the great potential of protein network-based approaches for
medical applications. With continued improvements in experimental techniques
to characterize such networks, they will without doubt play an important role in
the future of biomedicine.

5.

ACKNOWLEDGMENTS

I would like to thank the NIH for its support through grant GM63882-02.

6.

REFERENCES

1. Aebersold R, Goodlett DR. 2001. Mass spectrometry in proteomics. Chem Rev 101 :269-295.

2. Albert R, Jeong H, Barabási AL. 2000. Error and attack tolerance of complex networks. Nature

406 :378-382.

3. Alon U, Barkai N, Notterman DA, Gish K, Ybarra S, Mack D, Levine AJ. 1999. Broad pat-

terns of gene expression revealed by clustering analysis of tumor and normal colon tissues
probed by oligonucleotide arrays. Proc Natl Acad Sci USA 96 :6745-6750.

4. Bartel PL, Roecklein JA, SenGupta D, Fields S. 1996. A protein linkage map of Escherichia

coli bacteriophage T7. Nature Genet 12 :72-77.