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

Chapter 8
Conclusion and Future
Directions
8.1 Conclusion
In this thesis we have described a new pipeline for preprocessing, processing
and analysis of Time-Of-Flight Mass Spectrometry proteomics data. We have
shown the application of this web-based framework in the area of clinical
diagnostics to detect molecular patterns (fingerprints) of diseases and used
these to classify unknown datasets (spectra). Newly developed algorithms
allow the detection of very small signals that presumably represent very low
abundant molecules, such as hormones. Fingerprints including these very
small signals can be much more sensitive compared to standard approaches
that do not detect them.
The datasets are typically very large (several Gigabytes per patient). To
enable handling of these large datasets we have also introduced a new distributed
computing platform that allows creation of heterogeneous ad-hoc
Grids. To demonstrate the universality of this framework we have shown in
a case study the integration of a Playstation 3 to perform data preprocessing
tasks.
In the current stage of this work it is possible to reliably detect multicomponent
fingerprints for a given disease. The components of a fingerprint
represent particular molecular species (peptides or proteins) contained in some
body fluid (e.g. blood serum) that significantly differentiate in concentration
between two patient groups, such as healthy vs. diseased. These molecules -
once identified - can be used as so called biomarkers. A biomarker is defined
as a molecular, biological or physical characteristic (e.g. DNA sequences,
antibodies or - as in our case - proteins) that indicates a specific physiologic
state which can be directly linked to the clinical manifestations and outcome
of a particular disease.
After identification of a disease specific set of biomarkers subsequent studies
can be designed to eventually find drugs that can target these biomarkers
and hopefully open up new steps for actually curing this disease.
However, until this vision becomes reality there are some open problems
that need further investigation to allow for a deeper understanding and thus reliable
and comprehensible mass-spectrometry based clinical diagnostics. These
open problems include:
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