title: PAGER: constructing PAGs and new PAG-PAG relationships for network biology.
abstract: In this article, we described a new database framework to perform integrative "gene-set, network, and pathway analysis" (GNPA). In this framework, we integrated heterogeneous data on pathways, annotated list, and gene-sets (PAGs) into a PAG electronic repository (PAGER). PAGs in the PAGER database are organized into P-type, A-type and G-type PAGs with a three-letter-code standard naming convention. The PAGER database currently compiles 44 313 genes from 5 species including human, 38 663 PAGs, 324 830 gene-gene relationships and two types of 3 174 323 PAG-PAG regulatory relationships-co-membership based and regulatory relationship based. To help users assess each PAG's biological relevance, we developed a cohesion measure called Cohesion Coefficient (CoCo), which is capable of disambiguating between biologically significant PAGs and random PAGs with an area-under-curve performance of 0.98. PAGER database was set up to help users to search and retrieve PAGs from its online web interface. PAGER enable advanced users to build PAG-PAG regulatory networks that provide complementary biological insights not found in gene set analysis or individual gene network analysis. We provide a case study using cancer functional genomics data sets to demonstrate how integrative GNPA help improve network biology data coverage and therefore biological interpretability. The PAGER database can be accessible openly at http://discovery.informatics.iupui.edu/PAGER/.
authors.affiliation: Indiana University School of Informatics and Computing, Department of Computer and Information Science, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, Purdue University Center for Cancer Research, West Lafayette, IN 47906 and Institute of Biopharmaceutical Informatics and Technology, Wenzhou Medical University, WenZhou, Zhe Jiang Province, China.
authors.forename: Zongliang
authors.initials: Z
authors.lastname: Yue
authors.affiliation: Indiana University School of Informatics and Computing, Department of Computer and Information Science, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, Purdue University Center for Cancer Research, West Lafayette, IN 47906 and Institute of Biopharmaceutical Informatics and Technology, Wenzhou Medical University, WenZhou, Zhe Jiang Province, China.
authors.forename: Madhura M
authors.initials: MM
authors.lastname: Kshirsagar
authors.affiliation: Indiana University School of Informatics and Computing, Department of Computer and Information Science, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, Purdue University Center for Cancer Research, West Lafayette, IN 47906 and Institute of Biopharmaceutical Informatics and Technology, Wenzhou Medical University, WenZhou, Zhe Jiang Province, China.
authors.forename: Thanh
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: Indiana University School of Informatics and Computing, Department of Computer and Information Science, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, Purdue University Center for Cancer Research, West Lafayette, IN 47906 and Institute of Biopharmaceutical Informatics and Technology, Wenzhou Medical University, WenZhou, Zhe Jiang Province, China.
authors.forename: Chayaporn
authors.initials: C
authors.lastname: Suphavilai
authors.affiliation: Indiana University School of Informatics and Computing, Department of Computer and Information Science, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, Purdue University Center for Cancer Research, West Lafayette, IN 47906 and Institute of Biopharmaceutical Informatics and Technology, Wenzhou Medical University, WenZhou, Zhe Jiang Province, China.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Neylon
authors.affiliation: Indiana University School of Informatics and Computing, Department of Computer and Information Science, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, Purdue University Center for Cancer Research, West Lafayette, IN 47906 and Institute of Biopharmaceutical Informatics and Technology, Wenzhou Medical University, WenZhou, Zhe Jiang Province, China.
authors.forename: Liugen
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Indiana University School of Informatics and Computing, Department of Computer and Information Science, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, Purdue University Center for Cancer Research, West Lafayette, IN 47906 and Institute of Biopharmaceutical Informatics and Technology, Wenzhou Medical University, WenZhou, Zhe Jiang Province, China.
authors.forename: Timothy
authors.initials: T
authors.lastname: Ratliff
authors.affiliation: Indiana University School of Informatics and Computing, Department of Computer and Information Science, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, Purdue University Center for Cancer Research, West Lafayette, IN 47906 and Institute of Biopharmaceutical Informatics and Technology, Wenzhou Medical University, WenZhou, Zhe Jiang Province, China Indiana University School of Informatics and Computing, Department of Computer and Information Science, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, Purdue University Center for Cancer Research, West Lafayette, IN 47906 and Institute of Biopharmaceutical Informatics and Technology, Wenzhou Medical University, WenZhou, Zhe Jiang Province, China Indiana University School of Informatics and Computing, Department of Computer and Information Science, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, Purdue University Center for Cancer Research, West Lafayette, IN 47906 and Institute of Biopharmaceutical Informatics and Technology, Wenzhou Medical University, WenZhou, Zhe Jiang Province, China.
authors.forename: Jake Y
authors.initials: JY
authors.lastname: Chen
mesh_terms: D030541:Databases, Genetic; D053263:Gene Regulatory Networks; D006801:Humans; D012984:Software