title: PINTnet: construction of condition-specific pathway interaction network by computing shortest paths on weighted PPI.
abstract: Identifying perturbed pathways in a given condition is crucial in understanding biological phenomena. In addition to identifying perturbed pathways individually, pathway analysis should consider interactions among pathways. Currently available pathway interaction prediction methods are based on the existence of overlapping genes between pathways, protein-protein interaction (PPI) or functional similarities. However, these approaches just consider the pathways as a set of genes, thus they do not take account of topological features. In addition, most of the existing approaches do not handle the explicit gene expression quantity information that is routinely measured by RNA-sequecing.
  
  
  
  To overcome these technical issues, we developed a new pathway interaction network construction method using PPI, closeness centrality and shortest paths. We tested our approach on three different high-throughput RNA-seq data sets: pregnant mice data to reveal the role of serotonin on beta cell mass, bone-metastatic breast cancer data and autoimmune thyroiditis data to study the role of IFN- α. Our approach successfully identified the pathways reported in the original papers. For the pathways that are not directly mentioned in the original papers, we were able to find evidences of pathway interactions by the literature search. Our method outperformed two existing approaches, overlapping gene-based approach (OGB) and protein-protein interaction-based approach (PB), in experiments with the three data sets.
  
  
  
  Our results show that PINTnet successfully identified condition-specific perturbed pathways and the interactions between the pathways. We believe that our method will be very useful in characterizing biological mechanisms at the pathway level. PINTnet is available at http://biohealth.snu.ac.kr/software/PINTnet/ .
authors.affiliation: Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, Republic of Korea.
authors.forename: Ji Hwan
authors.initials: JH
authors.lastname: Moon
authors.affiliation: Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, Republic of Korea.
authors.forename: Sangsoo
authors.initials: S
authors.lastname: Lim
authors.affiliation: Department of Computer Science & Engineering, Seoul National University, Seoul, Republic of Korea.
authors.forename: Kyuri
authors.initials: K
authors.lastname: Jo
authors.affiliation: Department of Computer Science & Engineering, Seoul National University, Seoul, Republic of Korea.
authors.forename: Sangseon
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Computer Science & Engineering, Seoul National University, Seoul, Republic of Korea.
authors.forename: Seokjun
authors.initials: S
authors.lastname: Seo
authors.affiliation: Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, Republic of Korea. sunkim.bioinfo@snu.ac.kr.|Department of Computer Science & Engineering, Seoul National University, Seoul, Republic of Korea. sunkim.bioinfo@snu.ac.kr.|Bioinformatics Institute, Seoul National University, Seoul, Republic of Korea. sunkim.bioinfo@snu.ac.kr.
authors.forename: Sun
authors.initials: S
authors.lastname: Kim
mesh_terms: D019295:Computational Biology / Q000379:methods*; D005786:Gene Expression Regulation; D000069550:Machine Learning; D025941:Protein Interaction Mapping / Q000379:methods*
keywords: Closeness centrality; Gene expression; Pathway interaction; Protein-protein interaction; Shortest path