Abstract: Cellular complexity stems from the interactions
among thousands of different molecular species. Thanks to the
emerging fields of systems and synthetic biology, scientists are
beginning to unravel these regulatory, signaling, and metabolic
interactions and to understand their coordinated action. Reverse
engineering of biological networks has has several benefits but a
poor quality of data combined with the difficulty in reproducing
it limits the applicability of these methods. A few years back,
many of the commonly used predictive algorithms were tested
on a network constructed in the yeast Saccharomyces cerevisiae
(S. cerevisiae) to resolve this issue. The network was a synthetic
network of five genes regulating each other for the so-called in
vivo reverse-engineering and modeling assessment (IRMA). The
network was constructed in S. cereviase since it is a simple and well
characterized organism. The synthetic network included a variety
of regulatory interactions, thus capturing the behaviour of larger
eukaryotic gene networks on a smaller scale. We derive a new set of
algorithms by solving a nonlinear optimization problem and show
how these algorithms outperform other algorithms on these datasets.
Abstract: Gene networks present a graphical view at the level of gene activities and genetic functions and help us to understand complex interactions in a meaningful manner. In the present study, we have analyzed the gene interaction of PPAR-γ (peroxisome proliferator-activated receptor gamma) by search tool for retrieval of interacting genes. We find PPAR-γ is highly networked by genetic interactions with 10 genes: RXRA (retinoid X receptor, alpha), PPARGC1A (peroxisome proliferator-activated receptor gamma, coactivator 1 alpha), NCOA1 (nuclear receptor coactivator 1), NR0B2 (nuclear receptor subfamily 0, group B, member 2), HDAC3 (histone deacetylase 3), MED1 (mediator complex subunit 1), INS (insulin), NCOR2 (nuclear receptor co-repressor 2), PAX8 (paired box 8), ADIPOQ (adiponectin) and it augurs well for the fact that obesity and several other metabolic disorders are inter related.
Abstract: The goal of Gene Expression Analysis is to understand the processes that underlie the regulatory networks and pathways controlling inter-cellular and intra-cellular activities. In recent times microarray datasets are extensively used for this purpose. The scope of such analysis has broadened in recent times towards reconstruction of gene networks and other holistic approaches of Systems Biology. Evolutionary methods are proving to be successful in such problems and a number of such methods have been proposed. However all these methods are based on processing of genotypic information. Towards this end, there is a need to develop evolutionary methods that address phenotypic interactions together with genotypic interactions. We present a novel evolutionary approach, called Phenomic algorithm, wherein the focus is on phenotypic interaction. We use the expression profiles of genes to model the interactions between them at the phenotypic level. We apply this algorithm to the yeast sporulation dataset and show that the algorithm can identify gene networks with relative ease.
Abstract: A gene network gives the knowledge of the regulatory
relationships among the genes. Each gene has its activators and
inhibitors that regulate its expression positively and negatively
respectively. Genes themselves are believed to act as activators and
inhibitors of other genes. They can even activate one set of genes and
inhibit another set. Identifying gene networks is one of the most
crucial and challenging problems in Bioinformatics. Most work done
so far either assumes that there is no time delay in gene regulation or
there is a constant time delay. We here propose a Dynamic Time-
Lagged Correlation Based Method (DTCBM) to learn the gene
networks, which uses time-lagged correlation to find the potential
gene interactions, and then uses a post-processing stage to remove
false gene interactions to common parents, and finally uses dynamic
correlation thresholds for each gene to construct the gene network.
DTCBM finds correlation between gene expression signals shifted in
time, and therefore takes into consideration the multi time delay
relationships among the genes. The implementation of our method is
done in MATLAB and experimental results on Saccharomyces
cerevisiae gene expression data and comparison with other methods
indicate that it has a better performance.
Abstract: Using Dynamic Bayesian Networks (DBN) to model genetic regulatory networks from gene expression data is one of the major paradigms for inferring the interactions among genes. Averaging a collection of models for predicting network is desired, rather than relying on a single high scoring model. In this paper, two kinds of model searching approaches are compared, which are Greedy hill-climbing Search with Restarts (GSR) and Markov Chain Monte Carlo (MCMC) methods. The GSR is preferred in many papers, but there is no such comparison study about which one is better for DBN models. Different types of experiments have been carried out to try to give a benchmark test to these approaches. Our experimental results demonstrated that on average the MCMC methods outperform the GSR in accuracy of predicted network, and having the comparable performance in time efficiency. By proposing the different variations of MCMC and employing simulated annealing strategy, the MCMC methods become more efficient and stable. Apart from comparisons between these approaches, another objective of this study is to investigate the feasibility of using DBN modeling approaches for inferring gene networks from few snapshots of high dimensional gene profiles. Through synthetic data experiments as well as systematic data experiments, the experimental results revealed how the performances of these approaches can be influenced as the target gene network varies in the network size, data size, as well as system complexity.
Abstract: In this paper we investigate the influence of external
noise on the inference of network structures. The purpose of our
simulations is to gain insights in the experimental design of microarray
experiments to infer, e.g., transcription regulatory networks
from microarray experiments. Here external noise means, that the
dynamics of the system under investigation, e.g., temporal changes of
mRNA concentration, is affected by measurement errors. Additionally
to external noise another problem occurs in the context of microarray
experiments. Practically, it is not possible to monitor the mRNA
concentration over an arbitrary long time period as demanded by the
statistical methods used to learn the underlying network structure. For
this reason, we use only short time series to make our simulations
more biologically plausible.