Abstract

Integrative Gene-set, Network and Pathway Analysis (GNPA) is a powerful data analysis approach developed to help interpret high-throughput omics data. In PAGER 1.0, we demonstrated that researchers can gain unbiased and reproducible biological insights with the introduction of PAGs (Pathways, Annotated-lists and Gene-signatures) as the basic data representation elements. In PAGER 2.0, we improve the utility of integrative GNPA by significantly expanding the coverage of PAGs and PAG-to-PAG relationships in the database, defining a new metric to quantify PAG data qualities, and developing new software features to simplify online integrative GNPA. Specifically, we included 84 282 PAGs spanning 24 different data sources that cover human diseases, published gene-expression signatures, drug–gene, miRNA–gene interactions, pathways and tissue-specific gene expressions. We introduced a new normalized Cohesion Coefficient (nCoCo) score to assess the biological relevance of genes inside a PAG, and RP-score to rank genes and assign gene-specific weights inside a PAG. The companion web interface contains numerous features to help users query and navigate the database content. The database content can be freely downloaded and is compatible with third-party Gene Set Enrichment Analysis tools. We expect PAGER 2.0 to become a major resource in integrative GNPA. PAGER 2.0 is available at http://discovery.informatics.uab.edu/PAGER/.

Highlights

  • In a biological system, multiple genes and proteins regulate in concert to exert specific processes [1,2,3]

  • In PAGER 2.0, we provide a major update for PAGER to provide substantially expanded PAG data coverage, a new normalized quality score metric called normalized Cohesion Coefficient (nCoCo) to assess the biological relevance of genes inside each PAG, and a new user-friendly interface to help users perform integrative GNPA queries

  • Genes act in concert to drive various biological processes in a complex biological system

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Summary

INTRODUCTION

Multiple genes and proteins regulate in concert to exert specific processes [1,2,3]. CoCo nCoCo miss’ analysis––a laborious process requiring manual evaluations [2,12,13,14,15] To overcome these challenges, we previously developed PAGER, a novel and comprehensive database infrastructure by integrating PAGs––a new unified data structure to represent heterogeneous Pathways (P-type), Annotated-lists (A-type) and Gene-signatures (G-type) [11]. To assist users in prioritizing genes in the PAGs, we integrated the functional gene–gene interaction data from the recently published HAPPI-2 database [16] to generate a gene ranking score (RP-score) [17] based on the biological context-specific study. We intend for PAGER 2.0 to become a major resource for researchers interested in integrative GNPA

MATERIALS AND METHODS
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