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

Chapter 1
Introduction and Survey
1.1 Introduction
The Postgenomic Era
The successful completion of the Human Genome Project, which identified
and mapped (almost) the entire collection of human genes (the genome), has
uncovered an amazing amount of information. However, this information did Genome Project: foundation for real
only build up the foundation for further exploration to ultimately answer the
fundamental question biologists are interested in: How do the genes in the
genome work together in a human being ?
Although this and related projects (and genetics in general) have received
much attention during the last couple of years one should not forget that the
question: how do genes work in
humans?
primary purpose of most genes is to code for proteins. Whereas gene structure Gene’s purpose: code for proteins
and organization are important, the fate of a cell (and thus of each organism)
is determined by specific proteins and some RNAs (Pandey and Mann, 2000). Proteins determine fate of a cell
They execute and control the majority of cellular activities and are the targets
of nearly all our drugs. Realizing this, the primary focus of biologists is shifting Biologist’s focus shifts to proteins
towards the proteome, the set of all proteins the human genome can produce.
More specifically, the proteome is the set of expressed proteins at a given point
in time under specific conditions - and thus dynamic. A snapshot of a cells Proteome (= set of all proteins)
becomes main topic
proteome provides information about the ensemble of proteins active in that Cell proteome provides temporal
information about cell state
cell at that time under the given specific physiological conditions (Wasinger
et al., 1995; Wilkins et al., 1996; Naaby-Hansen et al., 2005).
Unfortunately, switching from genes to proteins adds some orders of magnitude
to the complexity of the problem: While the human genome is estimated
to contain approximately 30.000-40.000 genes that code for proteins,
the corresponding number of proteins these genes encode for is much higher.
Events such as alternative splicing of genes and post-translational modifica- 3 · 10 4 genes vs. 10 6 proteins
tions generate a highly diverse set of proteins that could exceed a million
distinct molecular species within a given cell. Most of these being yet uncharacterized
(Whisstock and Lesk, 2003).
The Proteomics Era
Bringing proteins into the center of attention, the fundamental question from
the first paragraph now turns into: What is the specific purpose of each protein,
how do they interact with each other, how are they modified and how
can we change their actions therapeutically ? New main question: how do proteins
work in humans?
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