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Addressing this problem has been made possible by recent advances
in genetic sequencing and development of a whole new generation of
sophisticated biological tools.
The most promising technique to date is based on the view of gene
systems as a logical network of nodes that influence each other's
expression levels. Consequently, one may obtain some information
on gene interactions in the network by measurement of gene
expression. The level of gene expression, i.e., the production
rate of a given protein changes during execution of a genetic
process involving it and can be monitored by several biological
experiments.
A variety of experimental tools have been developed recently with
the ability to observe the expression of many genes
simultaneously. At the forefront of these technologies lies the
DNA microarray, commonly used to monitor gene expression at the
level of mRNA abundance. Similarly, the rapid identification of
proteins and their abundances is becoming possible through methods
such as 2D polyacrylamide gel electrophoresis, 2-hybrid systems,
protein chips, etc. The main contribution of all of these
technologies is that numerous genes can be monitored in the same
experiment, making it possible to perform a global expression
analysis of the cell.
Additional information about a genetic network may be gleaned
experimentally by applying a directed perturbation to the network,
and observing expression levels of every gene in the network in
the presence of the perturbation. Perturbations may be
genetic, in which the expression levels of one or more
genes are fixed by knockout (removal of the gene) or
overexpression (higher than usual level of gene
expression), or biological, in which one or more
non-genetic factors are altered, such as a change in environment,
nutrition, or a temperature increase. Such biological experiments
are very costly and very few such perturbations may be performed
at one time. Thus, reducing the number and cost of experiments is
crucial.
Methods presented above supply biological data in terms of expression levels
of many genes at different time points and in different conditions.
The functional analysis of the data can be defined as a computational problem,
aiming to infer some plausible model of the network from the observations
with minimal number or cost of biological experiments. The model should
describe how the expression level of each gene in the network depends
on external stimuli and expression levels of other genes.
Additional goals include construction of a knowledge-base of gene regulatory networks,
verification of pathways or gene networks hypotheses.
Next: Gene Network Models
Up: Functional Analysis
Previous: Functional Analysis
Peer Itsik
2001-03-04