Inference of Biological Pathway from Gene Expression Profiles by Time Delay Boolean Networks

<div><p>One great challenge of genomic research is to efficiently and accurately identify complex gene regulatory networks. The development of high-throughput technologies provides numerous experimental data such as DNA sequences, protein sequence, and RNA expression profiles makes it possible to study interactions and regulations among genes or other substance in an organism. However, it is crucial to make inference of genetic regulatory networks from gene expression profiles and protein interaction data for systems biology. This study will develop a new approach to reconstruct time delay Boolean networks as a tool for exploring biological pathways. In the inference strategy, we will compare all pairs of input genes in those basic relationships by their corresponding -scores for every output gene. Then, we will combine those consistent relationships to reveal the most probable relationship and reconstruct the genetic network. Specifically, we will prove that state transition pairs are sufficient and necessary to reconstruct the time delay Boolean network of nodes with high accuracy if the number of input genes to each gene is bounded. We also have implemented this method on simulated and empirical yeast gene expression data sets. The test results show that this proposed method is extensible for realistic networks.</p> </div

The eight basic relationships and their probabilistic hypotheses and -scores.

<p>The eight basic relationships and their probabilistic hypotheses and -scores.</p

One example of time delay Boolean network and its input/output.

<p>One example of time delay Boolean network and its input/output.</p

Splitting counts caused by misclassification error.

<p>Splitting counts caused by misclassification error.</p

By the time delay Boolean network in Figure 1, we generate 100 samples with p = 0.05.

<p>By the time delay Boolean network in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042095#pone-0042095-g001" target="_blank">Figure 1</a>, we generate 100 samples with p = 0.05.</p

Count and probabilities table for , and with misclassification error.

<p>Count and probabilities table for , and with misclassification error.</p

Network reconstruct from the expression data of yeast Saccharomyces cerevisiae.

<p>Network reconstruct from the expression data of yeast Saccharomyces cerevisiae.</p

Boolean network <i>G</i>(<i>V,F</i>), wiring diagram <i>G′</i>(<i>V′,F′</i>) and its input/output.

<p>Boolean network <i>G</i>(<i>V,F</i>), wiring diagram <i>G′</i>(<i>V′,F′</i>) and its input/output.</p