Network Inference
A major challenge of systems biology is to infer biochemical
interactions from large-scale observations, such as transcriptomics,
proteomics and metabolomics. Inferred interactions are combined to yield
biochemical network models.
The main idea behind network inferrence from large-scale observations is
rather simple: 1) establish cause effect relationships between genes,
using for example genetic perturbations and then 2) distinguish between
direct and indirect causal effects. The final network model contains
only links that correspond to direct causal effects.
Several methods for inference of such networks from experimental data
have been proposed in the recent literature. Sometimes it is assumed
that biochemical networks can be modeled as directed acyclic graphs
(DAGs) which makes techniques such as Bayesian Networks applicable.
However, cyclic network structures, such as feedback loops, are
ubiquitous in biology and are associated with many of the specific
properties of living systems, and therefore analyses should be
independent of such assumptions.
Our main focus is on developing algorithms for gene network inference by
integrative analysis of gene expression and genotyping data, so called
Genetical Genomics. In this setup genotypes can be seen as
multifactorial perturbations causing variation in gene expression levels
which can be used to establish cause effect relationships. We employ
techniques such as Gaussian Graphical Models and the related technique
of Structural Equation Modeling. In contrast to Bayesian Networks these
approaches do not rely on the incorrect assumption that biochemical
networks are acyclic.