PAG stands for Pathway, Annotated-list and Gene-signature. A PAG geneset represents a set of genes that share a common feature, whether they belong within the same pathway, share common biological processes, are co-differentially expressed under a particular condition of an experiment or clinical sample, or share a common downstream target or function.
Pathway and Annotated-list Gene-signature Electronic Repository (PAGER) is an online systems biology tool for constructing and visualizing gene and PAG networks from multiple PAG genesets.
PAGER was implemented by using PHP language version 5 and Codeigniter version 2.1.3. PAGER data was stored in Oracle 12g database maintained by Indiana University and was connected to PHP server by Oracle Instant Client software. P-value for each edge in PAGs' networks was computed on the fly by using hypergeometric function provided by PDL. For gene and PAGs' networks visualization in PAGER, cytoscape.js, a JavaScript graph library for network visualization.
PAGER currently contains a total of 113,830 PAGs from 37 data sources, and is being updated weekly. We welcome you to add your PAGs to PAGER ( link ).
For full breakdown on PAG sources, refer to the table below:
Version | Type | Source | Count | |
---|---|---|---|---|
v.1 updates | P | Reactome | 528 | 33412 |
MSigDB-c2(CP) | 1320 | |||
KEGG | 199 | |||
Spike | 28 | |||
PharmGKB | 102 | |||
WikiPathway | 144 | |||
NCI-Nature Curated | 132 | |||
BioCarta | 252 | |||
Protein Lounge | 388 | |||
A | MSigDB-c2(CGP),c3 | 6199 | ||
G | GeneSigDB | 2942 | ||
MSigDB-c4 | 858 | |||
GAD | 1671 | GWAS Catalog | 1230 | |
NGS Catalog | 56 | |||
N | Genome Data | 17363 | ||
v.2 updates | A | GOA | 21894 | 56140 |
GTEx | 92 | |||
Pfam | 1161 | |||
G | DSigDB | 22455 | ||
MSigDB-c7 | 4852 | |||
mirTARbase | 2603 | |||
PheWAS | 1358 | |||
Microcosm Targets | 851 | |||
TargetScan | 390 | |||
Isozyme | 484 | |||
v.3 updates | P | GeoMx Cancer Transcriptome Atlas | 110 | 24278 |
A | Cell | 22 | ||
G | I2D | 15874 | ||
HPA-PathologyAtlas | 20 | |||
HPA-TCGA | 7932 | |||
HPA-normProtein | 105 | |||
HPA-FANTOM5 | 45 | |||
HPA-normRNA | 43 | |||
HPA-RNAcon | 62 | |||
HPA-CellAtlas | 31 | |||
HPA-GTEx | 34 | |||
Total | 113830 |
PAGER has several unique features available:
For examples of how to use PAGER, please see Use Cases.
Users can perform a basic search query for PAGs in PAGER by entering a keyword or gene symbol into the search bar on the home page:
Users can enter a list of genes obtained from their experiment or other data source to order to search for related PAGs in PAGER:
The RP-score (standing for rank prioritization-score) is used to rank genes within the PAG, allowing for output of a PAGER-ranked gene list.
We use RP-score to calculate and assign the gene weight in every PAG:
where p and q are the indexes of proteins from the selected module, k is a constant (k=2 in this study). The term conf(p, q) is the interaction confidence score assigned by HAPPI-2, where conf(p, q) is between 0 and 1. N(p, q) holds the value of 1 if protein p interacts with q or the value of 0 if protein p does not interact with q. We then rank the genes by the RP-score to pull out potential important genes in the top rank list.
The nCoCo score takes into account PAG size bias when determining quality score of PAG results. Users can view PAGs similar to their queried gene list by nCoCo score by clicking on header arrows:
The nCoCo score represents a PAG quality metric and is improved from the initial CoCo score (a Cohesion Coefficient derived from the measure of statistically significant coverage of gene-gene functional correlations in gene pairs or gene trios) in our PAGER publication .
Yes! Users may refer to this link for detailed instructions.
Yes! Users may refer to this link for contribution.
We try to make the content submission procedures easy for the user. We recommend users to upload geneset data using one of the two forms we provide.
1. Differential gene expression format (DEG) : Differentially expressed genes from your bulk RNA-sequencing or single-cell sequencing experiments.
2. Literature-curation format (LIT) : Genesets curated from related literature/reviews in your research field.
Once you submit your file, you will receive an email with a receipt ID for your submission. You can use this receipt ID to email us about any questions or updates about your submission.
The PAGER API allows developers to analyze gene lists, get enrichment results, and download files of enrichment results. We provide a demo using two R scripts in performing the PAGER analysis using API.
Zongliang Yue, Madhura M. Kshirsagar, Thanh Nguyen, Chayaporn Suphavilai, Michael T. Neylon, Liugen Zhu, Timothy Ratliff, Jake Y. Chen, PAGER: constructing PAGs and new PAG–PAG relationships for network biology, Bioinformatics, Volume 31, Issue 12, 15 June 2015, Pages i250–i257, https://doi.org/10.1093/bioinformatics/btv265
Zongliang Yue, Qi Zheng, Michael T Neylon, Minjae Yoo, Jimin Shin, Zhiying Zhao, Aik Choon Tan, Jake Y Chen, PAGER 2.0: an update to the pathway, annotated-list and gene-signature electronic repository for Human Network Biology, Nucleic Acids Research, Volume 46, Issue D1, 4 January 2018, Pages D668–D676, https://doi.org/10.1093/nar/gkx1040