Learning time-varying interaction networks
Licentiate thesis, 2013
Most biological systems consist of several subcomponents which
interact with each other. These interactions govern the overall behaviour
of the system; and in turn vary over time and in response to internal
and external stress during the course of an experiment. Identifying such
time-varying networks promises new insight into transient interactions
and their role in the biological process. Traditional methods have
focussed on identifying a single interaction
network based on time series data, ignoring the dynamic rewiring of
the underlying network.
This thesis studies the problem of inferring time-varying interactions
in gene interaction networks based on gene microarray expression
data. With the advent of next generation sequencing techologies,
the amount of publicly available microarray expression data as well as other omics
data has grown tremendously. Further, the microarray data is often generated
from different experimental conditions or under network
perturbations. One of the current challenges in systems biology is
integration of data generated from different experimental conditions
and under different stresses towards understanding of the dynamic
interactome.
NETGEM, the first study included in this thesis describes a method for inference of
time-varying gene interaction network based on microarray expression
data under network perturbation. The method presents a probabilistic generative
model under the assumption that the changes in the interaction
network are caused by the changing functional roles of the interaction genes
during the course of a biological process. This is used to infer
time-varying interactions for a perturbation study in {\em
Saccharomyces cerevisiae\/}~(Baker's Yeast) under nutrient stress. The
inferred network agrees with experimental evidence as
well as identifying key transient interactions during the course of the experiment.
In the subsequent study, we present a survey chapter describing current approaches for
inference of time-varying biological networks based on node
observations. We give an overview of different methods in terms of the
underlying model assumptions and applicability under different
conditions. We also describe how recent advances in theory of
compressed sensing have led to development of new network inference methods with mild assumptions on network dynamics.
probabilistic graphical models
gene microarray expressions
dynamic interactome
time-varying interaction networks
Room HB2, Hörsalvägen 8, Chalmers University of Technology
Opponent: Dr. Jean-Philippe Vert, Director, Centre for Computational Biology, Mines ParisTech, Paris, France