New Statistical Algorithms for the Analysis of Mass - FU Berlin, FB MI ...

102 CHAPTER 4. (BIO-)MEDICAL APPLICATIONS
in human cancer research (see above) but also in understanding a biological
system. These studies usually aim at the identification of protein fingerprints
that characterize the difference between a system at the different stages. Below
we give some success stories in this area of mass spectrometry-based research.
Identification of Proteins in Kinase Pathways
A compelling example of the value of comparative proteomics for assigning
unique cellular functions to uncharacterized members of protein classes was
done by (Khan et al., 2005). They developed an innovative cell-biological strategy
based on mass spectrometry proteomics to enrich distinct sexual stages of
P.berghei life cycle that allowed the generation of high-quality cellular models
for in-depth analysis. The result of this study was the most comprehensive
inventory of sex-specific parasite proteins generated so far, including the discovery
of novel protein kinasis regulating sex-specific signalling pathways.
Identification of ATM/ATR candidates in DNA-damage Response
Pathways
An excellent example how quantative mass spectrometry-based methods can
used for mapping protein phosphorylation sites in proteomes is given by (Matsuoka
et al., 2007).
Identification of Proteins in Insulin Pathways
(Dong et al., 2007) show that quantitative mass-spectrometry-based proteomics
using stable isotope labelling can be applied to intact organisms, as well as
cell-culture preparations, thus greatly expanding the potential applications of
this method.
4.6.3 Fingerprinting the Influenza Virus
Influenza is still a deadly virus that continues to cause illness all over the world.
The Influenza type A virus (most virulent in humans) genome is contained on
eight single (non-paired) RNA strands that code for eleven proteins. One of
these proteins, HA, encodes hemaglutinin which determines the extent of an
infection into a host organism. Screening of the virus is necessary for the
development of effective vaccines, since even a point mutation in the HA gene
sequence can render a vaccine ineffective. Usual screening techniques such
as enzyme immunoassays, complement fixation and heagglutination inhibition
(HI) assays are quite time consuming and do not provide molecular details.
A recent paper by (Downard and Morrissey, 2007) introduces a new surveillance
approach for screening the structure and antigenicity of the virus. The
method is based on creation of MS and MS/MS spectra from the tryptic digest
of hemagglutin. The resulting MS fingerprints can be compared to reference
fingerprints and by analyzing the MS/MS spectra even the molecular structure
and sequence can be determined in a single step.