Methods and approaches in the topology-based analysis of biological pathways

作者：Mitrea Cristina; Taghavi Zeinab; Bokanizad Behzad; Hanoudi Samer; Tagett Rebecca; Donato Michele; Voichita Calin; Draghici Sorin^*

来源：Frontiers in Physiology, 2013, 4: 278.

DOI：10.3389/fphys.2013.00278

• pathway analysis
• topology
• signaling pathways
• metabolic pathways
• mathematical model
• network topology
• statistical significance

The goal of pathway analysis is to identify the pathways significantly impacted in a given phenotype. Many current methods are based on algorithms that consider pathways as simple gene lists, dramatically under-utilizing the knowledge that such pathways are meant to capture. During the past few years, a plethora of methods claiming to incorporate various aspects of the pathway topology have been proposed. These topology-based methods, sometimes referred to as %26quot;third generation,%26quot; have the potential to better model the phenomena described by pathways. Although there is now a large variety of approaches used for this purpose, no review is currently available to offer guidance for potential users and developers. This review covers 22 such topology-based pathway analysis methods published in the last decade. We compare these methods based on: type of pathways analyzed (e.g., signaling or metabolic), input (subset of genes, all genes, fold changes, gene p-values, etc.), mathematical models, pathway scoring approaches, output (one or more pathway scores, p-values, etc.) and implementation (web-based, standalone, etc.). We identify and discuss challenges, arising both in methodology and in pathway representation, including inconsistent terminology, different data formats, lack of meaningful benchmarks, and the lack of tissue and condition specificity.

• 出版日期2013