Abstract

BackgroundPathway analysis is one of the later stage data analysis steps essential in interpreting high-throughput gene expression data. We propose a set of algorithms which given gene expression data can recognize which portion of sub-pathways are actively utilized in the biological system being studied. The degree of activation is measured by conditional probability of the input expression data based on the Bayesian Network model constructed from the topological pathway.ResultsWe demonstrate the effectiveness of our pathway analysis method by conducting two case studies. The first one applies our method to a well-studied temporal microarray data set for the cell cycle using the KEGG Cell Cycle pathway. Our method closely reproduces the biological claims associated with the data sets, but unlike the original work ours can produce how pathway routes interact with each other above and beyond merely identifying which pathway routes are involved in the process. The second study applies the method to the p53 mutation microarray data to perform a comparative study.ConclusionsWe show that our method achieves comparable performance against all other pathway analysis systems included in this study in identifying p53 altered pathways. Our method could pave a new way of carrying out next generation pathway analysis.

Highlights

  • Pathway analysis is one of the later stage data analysis steps essential in interpreting high-throughput gene expression data

  • The conditional probability tables (CPT) corresponding to these two edges are determined by the type of edge eij in G∗: activation or inhibition

  • Since scientists who use Kyoto Encyclopedia of Genes and Genomes (KEGG) graphs are not familiar with this rendering, we show in Fig. 3 the original KEGG Cell Cycle graph with routes identified in Table 3 for each cell cycle annotated in different colors, purple for G1, blue for S, yellow for G2 and orange for M

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Summary

Introduction

Pathway analysis is one of the later stage data analysis steps essential in interpreting high-throughput gene expression data. The goal of this paper is to report the extension of our previous work [18, 19] in which multiple new algorithms are introduced to isolate highly regulating (activation and/or suppression) sub-components of the pathways and conveniently visualize the overall patterns of pathway activation or suppression directly over the pathway diagrams. We call this system Deep Pathway Analyzer (DPA)

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