AUTHOR=Mitrea Cristina , Taghavi Zeinab , Bokanizad Behzad , Hanoudi Samer , Tagett Rebecca , Donato Michele , Voichita Calin , Draghici Sorin 

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

JOURNAL=Frontiers in Physiology

VOLUME=Volume 4 - 2013

YEAR=2013

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2013.00278

DOI=10.3389/fphys.2013.00278

ISSN=1664-042X

ABSTRACT=The goal of pathway analysis is to identify the  pathways significantly impacted in a given phenotype. Many current methods are based on algorithms which 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 ``third generation'', 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, stand alone, 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.