title: SPATIAL: A System-level PAThway Impact AnaLysis approach.
abstract: The goal of pathway analysis is to identify the pathways that are significantly impacted when a biological system is perturbed, e.g. by a disease or drug. Current methods treat pathways as independent entities. However, many signals are constantly sent from one pathway to another, essentially linking all pathways into a global, system-wide complex. In this work, we propose a set of three pathway analysis methods based on the impact analysis, that performs a system-level analysis by considering all signals between pathways, as well as their overlaps. Briefly, the global system is modeled in two ways: (i) considering the inter-pathway interaction exchange for each individual pathways, and (ii) combining all individual pathways to form a global, system-wide graph. The third analysis method is a hybrid of these two models. The new methods were compared with DAVID, GSEA, GSA, PathNet, Crosstalk and SPIA on 23 GEO data sets involving 19 tissues investigated in 12 conditions. The results show that both the ranking and the P-values of the target pathways are substantially improved when the analysis considers the system-wide dependencies and interactions between pathways.
authors.affiliation: Department of Computer Science, Wayne State University, Detroit, MI 48202, USA behzad@wayne.edu.
authors.forename: Behzad
authors.initials: B
authors.lastname: Bokanizad
authors.affiliation: Department of Computer Science, Wayne State University, Detroit, MI 48202, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Tagett
authors.affiliation: Department of Computer Science, Wayne State University, Detroit, MI 48202, USA.
authors.forename: Sahar
authors.initials: S
authors.lastname: Ansari
authors.affiliation: Department of Computer Science, Wayne State University, Detroit, MI 48202, USA.
authors.forename: B Hoda
authors.initials: BH
authors.lastname: Helmi
authors.affiliation: Department of Computer Science, Wayne State University, Detroit, MI 48202, USA Department of Obstetrics & Gynecology, Wayne State University, Detroit, MI 48202, USA.
authors.forename: Sorin
authors.initials: S
authors.lastname: Draghici
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D020869:Gene Expression Profiling / Q000379:methods; D053263:Gene Regulatory Networks; D006801:Humans; D053858:Metabolic Networks and Pathways; D015203:Reproducibility of Results; D015398:Signal Transduction