NDExR - R implementaion for NDEx server API
2024-10-29
Contents
1 Introduction
Networks are a powerful and flexible methodology for expressing biological knowledge for computation and communication. Albeit its benefits, the sharing of networks, the collaboration on network curation, keeping track of changes between different network versions, and detecting different versions itself, still is a major problem in network biology.
The Network Data Exchange, or NDEx, is an open-source software framework to manipulate, store and exchange networks of various types and formats (Pratt et al., 2015, Cell Systems 1, 302-305, October 28, 2015 ©2015 Elsevier Inc. ScienceDirect). NDEx can be used to upload, share and publicly distribute networks, while providing an output in formats, that can be used by plenty of other applications.
The public NDEx server is a network data commons which provides pathway collections like the Pathway Interaction Database of the NCI (http://www.ndexbio.org/#/user/301a91c6-a37b-11e4-bda0-000c29202374) and the Cancer Cell Maps Initiative (http://www.ndexbio.org/#/user/b47268a6-8112-11e6-b0a6-06603eb7f303).
This package provides an interface to query the public NDEx server, as well as private installations, in order to upload, download or modify biological networks.
This document aims to help the user to install and benefit from the wide range of functionality of this implementation. The package makes use of the R implementation of the Cytoscape Cyberinfrastructure (CX) format by the RCX package. The RCX package provides functions to create, edit, and extend the networks in CX format and also for the lossless conversion of the networks from and to iGraph and Bioconductor graph objects.
The package is compatible with all NDEx API versions 1.3 and 2.x.
2 Installation
2.1 Installation from Bioconductor
if (!requireNamespace("BiocManager", quietly = TRUE)) {
install.packages("BiocManager")
}
BiocManager::install("ndexr")
library(ndexr)3 Quick Start
A short overview of the most important functions of the package:
## load the library!
library(ndexr)
## login to the NDEx server
ndexcon <- ndex_connect("username", "password")
## search the networks for 'EGFR'
networks <- ndex_find_networks(ndexcon, "EGFR")
head(networks, 3)## ownerUUID isReadOnly subnetworkIds isValid
## 1 363f49e0-4cf0-11e9-9f06-0ac135e8bacf TRUE NULL TRUE
## 2 0db1f2dc-103f-11e8-b939-0ac135e8bacf FALSE NULL TRUE
## 3 efbfa554-57b3-11ed-ae36-0ac135e8bacf FALSE NULL TRUE
## warnings isShowcase isCertified indexLevel hasLayout hasSample cxFileSize
## 1 NULL FALSE FALSE META TRUE FALSE 34989
## 2 NULL FALSE FALSE ALL TRUE FALSE 93381
## 3 NULL FALSE FALSE ALL TRUE FALSE 294641
## cx2FileSize name
## 1 23355 EGFR biology
## 2 71065 EGFR Signaling
## 3 149583 NeoPPI - EGFR
## properties
## 1 NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100630/bin/cbt1109_0777_fig001.jpg, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100630/figure/F1/, Figure 1, EGFR biology, Pathway Figure OCR, https://www.biorxiv.org/content/10.1101/2020.05.29.124503v1.full , pathway, Homo sapiens, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100630, Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab., PMC3100630__cbt1109_0777_fig001.jpg, PMC3100630, 2011, Waiver-No rights reserved (CC0), Toni M Brand, et al. Cancer Biol Ther. 2011 May 1;11(9):777-792. <b>Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab.</b> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100630" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100630</a>, <a href="https://identifiers.org/doid/DOID:6688">Autoimmune lymphoproliferative syndrome</a>, <a href="https://identifiers.org/doid/DOID:162">Cancer</a>, <a href="https://identifiers.org/doid/DOID:0050700">Cardiomyopathy</a>, <a href="https://identifiers.org/doid/DOID:1324">Lung cancer</a>, <a href="https://identifiers.org/doid/DOID:3490">Noonan syndrome</a>, <a href="https://identifiers.org/doid/DOID:2394">Ovarian cancer</a>, __NetworkImage, figureLink, figureNumber, figureTitle, methods, networkType, organism, paperLink, paperTitle, pfocrId, pmcId, publicationYear, rights, reference, disease, string, string, string, string, string, string, string, string, string, string, string, string, string, string, string
## 2 NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, {"signor": "http://signor.uniroma2.it/relation_result.php?id=", "BTO": "http://identifiers.org/bto/BTO:", "uniprot": "http://identifiers.org/uniprot/", "pubmed": "http://identifiers.org/pubmed/", "CID": "http://identifiers.org/pubchem.compound/", "SID": "http://identifiers.org/pubchem.substance/", "chebi": "http://identifiers.org/chebi/CHEBI:", "hgnc.symbol": "http://identifiers.org/hgnc.symbol/"}, ["SIGNOR-EGF"], Theodora Pavlidou, Homo Sapiens (human), Prof. Gianni Cesareni, Attribution-ShareAlike 4.0 International (CC BY-SA 4.0), <div>Perfetto L., <i>et al.</i></div><div><b>SIGNOR: a database of causal relationships between biological entities</b><i>.</i></div><div>Nucleic Acids Res. 2016 Jan 4;44(D1):D548-54</div><div><span><a href="https://doi.org/10.1093/nar/gkv1048" target="_blank">doi: 10.1093/nar/gkv1048</a></span></div>, ["pathway","Signalling Pathway"], <a href="https://github.com/ndexcontent/ndexsignorloader">ndexsignorloader 1.2.0</a>, 0.1, https://signor.uniroma2.it/pathway_browser.php?organism=&pathway_list=SIGNOR-EGF, Edges have been collapsed with attributes converted to lists with exception of direct attribute, @context, labels, author, organism, rightsHolder, rights, reference, networkType, prov:wasGeneratedBy, __normalizationversion, prov:wasDerivedFrom, notes, string, list_of_string, string, string, string, string, string, list_of_string, string, string, string, string
## 3 NA, NA, NA, Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), Andrey Ivanov, Ph.D.; Xiulei Mo, Ph.D.; Qiankun Niu, Ph.D.; Haian Fu, Ph.D., <p>Mo, X. <i>et al</i>. (2022). <b>Systematic discovery of mutation-directed neo-protein-protein interactions in cancer</b>.<br/> Cell 185(11):1974-1985<br/>doi: <a href="https://doi.org/10.1016/j.cell.2022.04.014">10.1016/j.cell.2022.04.014</a></p>, rights, rightsHolder, reference, string, string, string
## owner version completed
## 1 wikipathways 2020-02-24 TRUE
## 2 signor 28-Nov-2023 TRUE
## 3 ivanovlab 20221108 TRUE
## description
## 1 \n<p>EGFR biology. Ligand binding to domains I and III of the EGFR expose the dimerization loop in domain II and induce receptor homo- or hetero-dimerization. This process activates the intrinsic tyrosine kinase activity of the EGFR and leads to the phosphorylation of specific tyrosines on the cytoplasmic tails of the receptor pair. These phospho-tyrosines serve to recruit specific effector molecules containing SH2 or PTB domains. These effector molecules recruit and induce various signaling pathways including the PI3K/AKT (A), RAS/MAPK (A), PLCγ/PKC (B) and STAT (B) pathways. In addition, a less appreciated pathway, the nuclear EGFR signaling pathway (C), is initiated upon ligand binding and induces EGFR translocation to the nucleus where it behaves as a co-transcriptional activator regulating key genes such as Cox2, iNOS, B-myb, Aurora kinase A and Cyclin D1.</p>\n<p><img src="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100630/bin/cbt1109_0777_fig001.jpg" style="width: 100%;"></p>\n
## 2 The epidermal growth factor receptor (EGFR) signaling pathway regulates growth, survival, proliferation, and differentiation. The binding of extracellular ligands (EGF) induces homo and heterodimerization, transphosphorylation and activation of four ErbB family receptors: EGFR (ErbB1), ErbB2, ErbB3, and ErbB4. These events trigger a cascade of activation of downstream pathways that include, principally, the MAPK, Akt and JNK pathways, culminating in DNA synthesis and cell proliferation.
## 3 <p>The protein-protein interactions of <b>EGFR L858R</b> or <b>EGFR</b> wild type detected using the NanoLuc luciferase-based bioluminescence resonance energy transfer (BRETn) technology-based quantitative high-throughput differential screening (qHT-dS) platform. The qHT-dS allows comparative screening of wild-type and mutant allele counterparts for the detection of differential interactions with cancer-associated proteins in live mammalian cells.</p><p>To differentiate gain of interactions (Go-PPI) from loss of interactions (Lo-PPI), the difference between WT and MUT PPI curves were calculated to obtain differential scores (differential_score), corresponding p-values (pvalue_ds), and p-values adjusted for multiple comparisons (qvalue_ds).</p> <p>The <b>statistically significant</b> edges (ss-Go-PPI, light blue) were defined based on the differential_score > 1 and pvalue_ds < 0.01. For ss-Lo-PPI edges (light red) the differential_score < 1 and pvalue_ds < 0.01.<br/></p><p>The <b>high-stringency n</b>edges (hs-Go-PPI, blue or hs-Lo-PPI, red) include the statistically significant PPIs for which qvalue_ds < 0.01, and differential_score ≥ 1.5 or ≤ 1/1.5, respectively.</p><p></p><p>The hs-Go-PPI edges that were further confirmed in a single-lowest-dose assay were prioritized as <b>high-confidence</b> edges (hc-Go-PPI, dark blue).</p>
## visibility nodeCount edgeCount creationTime
## 1 PUBLIC 65 0 1.597477e+12
## 2 PUBLIC 32 61 1.617835e+12
## 3 PUBLIC 341 340 1.667847e+12
## externalId modificationTime isDeleted
## 1 2e619013-dec9-11ea-99da-0ac135e8bacf 1.624923e+12 FALSE
## 2 f71ab602-97f0-11eb-9e72-0ac135e8bacf 1.701221e+12 FALSE
## 3 17bf8f9a-5ecd-11ed-ae36-0ac135e8bacf 1.669050e+12 FALSE## UUID of the first search result
networkId <- networks[1, "externalId"]
networkId## [1] "2e619013-dec9-11ea-99da-0ac135e8bacf"## get summary of the network
ndex_network_get_summary(ndexcon, networkId)## $ownerUUID
## [1] "363f49e0-4cf0-11e9-9f06-0ac135e8bacf"
##
## $isReadOnly
## [1] TRUE
##
## $subnetworkIds
## list()
##
## $isValid
## [1] TRUE
##
## $warnings
## list()
##
## $isShowcase
## [1] FALSE
##
## $isCertified
## [1] FALSE
##
## $indexLevel
## [1] "META"
##
## $hasLayout
## [1] TRUE
##
## $hasSample
## [1] FALSE
##
## $cxFileSize
## [1] 34989
##
## $cx2FileSize
## [1] 23355
##
## $name
## [1] "EGFR biology"
##
## $properties
## subNetworkId
## 1 NA
## 2 NA
## 3 NA
## 4 NA
## 5 NA
## 6 NA
## 7 NA
## 8 NA
## 9 NA
## 10 NA
## 11 NA
## 12 NA
## 13 NA
## 14 NA
## 15 NA
## value
## 1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100630/bin/cbt1109_0777_fig001.jpg
## 2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100630/figure/F1/
## 3 Figure 1
## 4 EGFR biology
## 5 Pathway Figure OCR, https://www.biorxiv.org/content/10.1101/2020.05.29.124503v1.full
## 6 pathway
## 7 Homo sapiens
## 8 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100630
## 9 Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab.
## 10 PMC3100630__cbt1109_0777_fig001.jpg
## 11 PMC3100630
## 12 2011
## 13 Waiver-No rights reserved (CC0)
## 14 Toni M Brand, et al. Cancer Biol Ther. 2011 May 1;11(9):777-792. <b>Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab.</b> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100630" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100630</a>
## 15 <a href="https://identifiers.org/doid/DOID:6688">Autoimmune lymphoproliferative syndrome</a>, <a href="https://identifiers.org/doid/DOID:162">Cancer</a>, <a href="https://identifiers.org/doid/DOID:0050700">Cardiomyopathy</a>, <a href="https://identifiers.org/doid/DOID:1324">Lung cancer</a>, <a href="https://identifiers.org/doid/DOID:3490">Noonan syndrome</a>, <a href="https://identifiers.org/doid/DOID:2394">Ovarian cancer</a>
## predicateString dataType
## 1 __NetworkImage string
## 2 figureLink string
## 3 figureNumber string
## 4 figureTitle string
## 5 methods string
## 6 networkType string
## 7 organism string
## 8 paperLink string
## 9 paperTitle string
## 10 pfocrId string
## 11 pmcId string
## 12 publicationYear string
## 13 rights string
## 14 reference string
## 15 disease string
##
## $owner
## [1] "wikipathways"
##
## $version
## [1] "2020-02-24"
##
## $completed
## [1] TRUE
##
## $description
## [1] "\n<p>EGFR biology. Ligand binding to domains I and III of the EGFR expose the dimerization loop in domain II and induce receptor homo- or hetero-dimerization. This process activates the intrinsic tyrosine kinase activity of the EGFR and leads to the phosphorylation of specific tyrosines on the cytoplasmic tails of the receptor pair. These phospho-tyrosines serve to recruit specific effector molecules containing SH2 or PTB domains. These effector molecules recruit and induce various signaling pathways including the PI3K/AKT (A), RAS/MAPK (A), PLCγ/PKC (B) and STAT (B) pathways. In addition, a less appreciated pathway, the nuclear EGFR signaling pathway (C), is initiated upon ligand binding and induces EGFR translocation to the nucleus where it behaves as a co-transcriptional activator regulating key genes such as Cox2, iNOS, B-myb, Aurora kinase A and Cyclin D1.</p>\n<p><img src=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100630/bin/cbt1109_0777_fig001.jpg\" style=\"width: 100%;\"></p>\n "
##
## $visibility
## [1] "PUBLIC"
##
## $nodeCount
## [1] 65
##
## $edgeCount
## [1] 0
##
## $creationTime
## [1] 1.597477e+12
##
## $externalId
## [1] "2e619013-dec9-11ea-99da-0ac135e8bacf"
##
## $modificationTime
## [1] 1.624923e+12
##
## $isDeleted
## [1] FALSE## get the entire network as RCX object
rcx <- ndex_get_network(ndexcon, networkId)
## show the content (aspects) of the network
rcx$metaData## Meta-data:
## name version idCounter elementCount consistencyGroup
## 1 nodes 1.0 843074 65 1
## 2 nodeAttributes 1.0 NA 390 1
## 3 networkAttributes 1.0 NA 18 1
## 4 cartesianLayout 1.0 NA 65 1
## 5 cyVisualProperties 1.0 NA 3 1
## 6 cyHiddenAttributes 1.0 NA 1 1
## 7 cyTableColumn 1.0 NA 30 1## upload network as a new network to the NDEx server
networkId <- ndex_create_network(ndexcon, rcx)
## do some other fancy stuff with the network, then update the
## network on the server
networkId <- ndex_update_network(ndexcon, rcx)
## realize, you did bad things to the poor network, so better delete
## it on the server
ndex_delete_network(ndexcon, networkId)4 Connect to a server
First, establish an connection to the NDEx server. This object is required for most of the other ndexr functions, because it stores options and authentication details. It is possible to connect to the server anonymously or provide a username and password to enable further functionality. If you have set up your own NDEx server, you might change the host to your local installation.
## load the library
library(ndexr)
## connect anonymously
ndexcon <- ndex_connect()
## log in with user name and password
ndexconUser <- ndex_connect(username="username", password="password")
## specify the server
ndexconLocal <- ndex_connect(
username="username",
password="password",
host="localhost:8888/ndex/rest"
)
## manually change the api and connection configuration
ndexcon13 <- ndex_connect(ndexConf=ndex_config$Version_1.3)This package is developed following the structure of the documented api structure. For complete description of the NDEx server api see http://www.home.ndexbio.org/using-the-ndex-server-api/. The R functions are named by the category, context and function they fullfil. In the following, the usage is described in detail, and hopefully gives a better understanding of logic behind the naming convention of this package.
5 Find Networks
To explore or search the networks on an NDEx server, this package offers a function to retrieve a list of networks from the server.
## list networks on server
networks <- ndex_find_networks(ndexcon)As result you get a data.frame containing information of the networks.
names(networks)## [1] "ownerUUID" "isReadOnly" "subnetworkIds" "isValid"
## [5] "warnings" "isShowcase" "isCertified" "indexLevel"
## [9] "hasLayout" "hasSample" "cxFileSize" "cx2FileSize"
## [13] "name" "properties" "owner" "version"
## [17] "completed" "description" "visibility" "nodeCount"
## [21] "edgeCount" "creationTime" "externalId" "modificationTime"
## [25] "isDeleted" "doi" "cxFormat"networks[1:5, c("name", "externalId")]## name
## 1 Bioregistry
## 2 secRecon - Functional Topoly Network
## 3 secRecon - Protein-Protein Interactions Network
## 4 FGF23 signaling in hypophosphatemic rickets and related disorders - Homo sapiens
## 5 SARS-CoV CYTOKINE STORM
## externalId
## 1 860647c4-f7c1-11ec-ac45-0ac135e8bacf
## 2 4e7b9729-722a-11ef-ad6c-005056ae3c32
## 3 efb15b63-722c-11ef-ad6c-005056ae3c32
## 4 8ea45310-9072-11ef-af07-005056ae3c32
## 5 a5973d67-8bd2-11ef-af07-005056ae3c32It is possible to restrict the networks to a specific search string (e.g. “EGFR”), an account name (only networks of this account will be shown), or limit the number of fetched networks.
## list networks on server (same as previous)
networks <- ndex_find_networks(ndexcon, start = 0, size = 5)
## search for 'EGFR'
networksEgfr <- ndex_find_networks(ndexcon, searchString = "EGFR")
## same as previous
networksEgfr <- ndex_find_networks(ndexcon, "EGFR")
networksEgfr[1:3, ]## ownerUUID isReadOnly subnetworkIds isValid
## 1 363f49e0-4cf0-11e9-9f06-0ac135e8bacf TRUE NULL TRUE
## 2 0db1f2dc-103f-11e8-b939-0ac135e8bacf FALSE NULL TRUE
## 3 efbfa554-57b3-11ed-ae36-0ac135e8bacf FALSE NULL TRUE
## warnings isShowcase isCertified indexLevel hasLayout hasSample cxFileSize
## 1 NULL FALSE FALSE META TRUE FALSE 34989
## 2 NULL FALSE FALSE ALL TRUE FALSE 93381
## 3 NULL FALSE FALSE ALL TRUE FALSE 294641
## cx2FileSize name
## 1 23355 EGFR biology
## 2 71065 EGFR Signaling
## 3 149583 NeoPPI - EGFR
## properties
## 1 NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100630/bin/cbt1109_0777_fig001.jpg, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100630/figure/F1/, Figure 1, EGFR biology, Pathway Figure OCR, https://www.biorxiv.org/content/10.1101/2020.05.29.124503v1.full , pathway, Homo sapiens, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100630, Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab., PMC3100630__cbt1109_0777_fig001.jpg, PMC3100630, 2011, Waiver-No rights reserved (CC0), Toni M Brand, et al. Cancer Biol Ther. 2011 May 1;11(9):777-792. <b>Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab.</b> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100630" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100630</a>, <a href="https://identifiers.org/doid/DOID:6688">Autoimmune lymphoproliferative syndrome</a>, <a href="https://identifiers.org/doid/DOID:162">Cancer</a>, <a href="https://identifiers.org/doid/DOID:0050700">Cardiomyopathy</a>, <a href="https://identifiers.org/doid/DOID:1324">Lung cancer</a>, <a href="https://identifiers.org/doid/DOID:3490">Noonan syndrome</a>, <a href="https://identifiers.org/doid/DOID:2394">Ovarian cancer</a>, __NetworkImage, figureLink, figureNumber, figureTitle, methods, networkType, organism, paperLink, paperTitle, pfocrId, pmcId, publicationYear, rights, reference, disease, string, string, string, string, string, string, string, string, string, string, string, string, string, string, string
## 2 NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, {"signor": "http://signor.uniroma2.it/relation_result.php?id=", "BTO": "http://identifiers.org/bto/BTO:", "uniprot": "http://identifiers.org/uniprot/", "pubmed": "http://identifiers.org/pubmed/", "CID": "http://identifiers.org/pubchem.compound/", "SID": "http://identifiers.org/pubchem.substance/", "chebi": "http://identifiers.org/chebi/CHEBI:", "hgnc.symbol": "http://identifiers.org/hgnc.symbol/"}, ["SIGNOR-EGF"], Theodora Pavlidou, Homo Sapiens (human), Prof. Gianni Cesareni, Attribution-ShareAlike 4.0 International (CC BY-SA 4.0), <div>Perfetto L., <i>et al.</i></div><div><b>SIGNOR: a database of causal relationships between biological entities</b><i>.</i></div><div>Nucleic Acids Res. 2016 Jan 4;44(D1):D548-54</div><div><span><a href="https://doi.org/10.1093/nar/gkv1048" target="_blank">doi: 10.1093/nar/gkv1048</a></span></div>, ["pathway","Signalling Pathway"], <a href="https://github.com/ndexcontent/ndexsignorloader">ndexsignorloader 1.2.0</a>, 0.1, https://signor.uniroma2.it/pathway_browser.php?organism=&pathway_list=SIGNOR-EGF, Edges have been collapsed with attributes converted to lists with exception of direct attribute, @context, labels, author, organism, rightsHolder, rights, reference, networkType, prov:wasGeneratedBy, __normalizationversion, prov:wasDerivedFrom, notes, string, list_of_string, string, string, string, string, string, list_of_string, string, string, string, string
## 3 NA, NA, NA, Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), Andrey Ivanov, Ph.D.; Xiulei Mo, Ph.D.; Qiankun Niu, Ph.D.; Haian Fu, Ph.D., <p>Mo, X. <i>et al</i>. (2022). <b>Systematic discovery of mutation-directed neo-protein-protein interactions in cancer</b>.<br/> Cell 185(11):1974-1985<br/>doi: <a href="https://doi.org/10.1016/j.cell.2022.04.014">10.1016/j.cell.2022.04.014</a></p>, rights, rightsHolder, reference, string, string, string
## owner version completed
## 1 wikipathways 2020-02-24 TRUE
## 2 signor 28-Nov-2023 TRUE
## 3 ivanovlab 20221108 TRUE
## description
## 1 \n<p>EGFR biology. Ligand binding to domains I and III of the EGFR expose the dimerization loop in domain II and induce receptor homo- or hetero-dimerization. This process activates the intrinsic tyrosine kinase activity of the EGFR and leads to the phosphorylation of specific tyrosines on the cytoplasmic tails of the receptor pair. These phospho-tyrosines serve to recruit specific effector molecules containing SH2 or PTB domains. These effector molecules recruit and induce various signaling pathways including the PI3K/AKT (A), RAS/MAPK (A), PLCγ/PKC (B) and STAT (B) pathways. In addition, a less appreciated pathway, the nuclear EGFR signaling pathway (C), is initiated upon ligand binding and induces EGFR translocation to the nucleus where it behaves as a co-transcriptional activator regulating key genes such as Cox2, iNOS, B-myb, Aurora kinase A and Cyclin D1.</p>\n<p><img src="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100630/bin/cbt1109_0777_fig001.jpg" style="width: 100%;"></p>\n
## 2 The epidermal growth factor receptor (EGFR) signaling pathway regulates growth, survival, proliferation, and differentiation. The binding of extracellular ligands (EGF) induces homo and heterodimerization, transphosphorylation and activation of four ErbB family receptors: EGFR (ErbB1), ErbB2, ErbB3, and ErbB4. These events trigger a cascade of activation of downstream pathways that include, principally, the MAPK, Akt and JNK pathways, culminating in DNA synthesis and cell proliferation.
## 3 <p>The protein-protein interactions of <b>EGFR L858R</b> or <b>EGFR</b> wild type detected using the NanoLuc luciferase-based bioluminescence resonance energy transfer (BRETn) technology-based quantitative high-throughput differential screening (qHT-dS) platform. The qHT-dS allows comparative screening of wild-type and mutant allele counterparts for the detection of differential interactions with cancer-associated proteins in live mammalian cells.</p><p>To differentiate gain of interactions (Go-PPI) from loss of interactions (Lo-PPI), the difference between WT and MUT PPI curves were calculated to obtain differential scores (differential_score), corresponding p-values (pvalue_ds), and p-values adjusted for multiple comparisons (qvalue_ds).</p> <p>The <b>statistically significant</b> edges (ss-Go-PPI, light blue) were defined based on the differential_score > 1 and pvalue_ds < 0.01. For ss-Lo-PPI edges (light red) the differential_score < 1 and pvalue_ds < 0.01.<br/></p><p>The <b>high-stringency n</b>edges (hs-Go-PPI, blue or hs-Lo-PPI, red) include the statistically significant PPIs for which qvalue_ds < 0.01, and differential_score ≥ 1.5 or ≤ 1/1.5, respectively.</p><p></p><p>The hs-Go-PPI edges that were further confirmed in a single-lowest-dose assay were prioritized as <b>high-confidence</b> edges (hc-Go-PPI, dark blue).</p>
## visibility nodeCount edgeCount creationTime
## 1 PUBLIC 65 0 1.597477e+12
## 2 PUBLIC 32 61 1.617835e+12
## 3 PUBLIC 341 340 1.667847e+12
## externalId modificationTime isDeleted
## 1 2e619013-dec9-11ea-99da-0ac135e8bacf 1.624923e+12 FALSE
## 2 f71ab602-97f0-11eb-9e72-0ac135e8bacf 1.701221e+12 FALSE
## 3 17bf8f9a-5ecd-11ed-ae36-0ac135e8bacf 1.669050e+12 FALSE## search for networks of a user
networksOfUser <- ndex_find_networks(ndexcon, accountName = "ndextutorials")
networksOfUser[1:5, c("name", "owner", "externalId")]## name owner
## 1 BNFO 286 (Homework) - Direct p53 effectors example ndextutorials
## 2 BNFO 286 - WNT Signaling ndextutorials
## 3 Metabolism ndextutorials
## 4 Metabolism of RNA ndextutorials
## 5 Metabolism of proteins ndextutorials
## externalId
## 1 57aac7d2-d959-11ed-b4a3-005056ae23aa
## 2 ff9c05f4-b502-11ec-b3be-0ac135e8bacf
## 3 3bd76cf4-c4a1-11e4-bcc4-000c29cb28fb
## 4 c9243cce-2d32-11e8-b939-0ac135e8bacf
## 5 4197cc9c-c4a6-11e4-bcc4-000c29cb28fb6 Simple network operations
To both, users and networks stored on an NDEx server, a universally
unique identifier (UUID) is assigned. Although both have the same format
(i.e. “xxxxxxxx-xxxx-xxxx-xxxx-xxxxxxxxxxxx”, where x is one of
[a-z0-9]), it has to be distinguished between the user UUID and the
network UUID, but the difference is obvious by the context. Within RCX
objects and search results, the network UUID is also referred to as
“externalId” (see previous section). This UUID can be
used to access a network on the server and retrieve just a summary of
the network (similar to the results of a network search) or even the
entire network as RCX object (see next section).
Since networks can contain many nodes and edges, and a huge amount of other attributes, it is typically advisable to first get a network summary, to check the node and edge counts for a network before retrieving the entire network. Thereby the structure of the network summary is similar the structure of the network list
## UUID of the first search result
networkId <- networksOfUser[1, "externalId"]
## get network summary
networkSummary <- ndex_network_get_summary(ndexcon, networkId)
names(networkSummary)## [1] "ownerUUID" "isReadOnly" "subnetworkIds" "isValid"
## [5] "warnings" "isShowcase" "isCertified" "indexLevel"
## [9] "hasLayout" "hasSample" "cxFileSize" "cx2FileSize"
## [13] "name" "properties" "owner" "version"
## [17] "completed" "description" "visibility" "nodeCount"
## [21] "edgeCount" "creationTime" "externalId" "modificationTime"
## [25] "isDeleted"networkSummary[c("name", "externalId")]## $name
## [1] "BNFO 286 (Homework) - Direct p53 effectors example"
##
## $externalId
## [1] "57aac7d2-d959-11ed-b4a3-005056ae23aa"## get the entire network as RCX object
rcx <- ndex_get_network(ndexcon, networkId)
rcx$metaData## Meta-data:
## name version idCounter elementCount consistencyGroup
## 1 nodes 1.0 146 146 1
## 2 edges 1.0 537 215 1
## 3 nodeAttributes 1.0 NA 287 1
## 4 edgeAttributes 1.0 NA 595 1
## 5 networkAttributes 1.0 NA 5 1
## 6 cartesianLayout 1.0 NA 146 1
## 7 cyVisualProperties 1.0 NA 3 1
## 8 cyHiddenAttributes 1.0 NA 3 1
## 9 cyTableColumn 1.0 NA 16 1To send a network to an server, there are two possibilities. Either one wants to update an existing network on the server or create a new one. In both cases, a UUID is returned, either of the updated network or a newly generated one for the created network. For updating a network, the UUID is extracted from the “externalId” property of the “ndexStatus” aspect, or can be set manually.
## create a new network on server
networkId <- ndex_create_network(ndexcon, rcx)
## update a network on server
networkId <- ndex_update_network(ndexcon, rcx)
## same as previous
networkId <- ndex_update_network(ndexcon, rcx, networkId)Besides creating, reading and updating, it is also possible to delete networks on the server. This operation cannot be undone, so be careful!
## deletes the network from the server
ndex_delete_network(ndexcon, networkId)7 RCX
For the exchange of network data, NDEx uses the Cytoscape
Cyberinfrastructure Network Interchange Format, or just CX format (See
http://www.home.ndexbio.org/data-model/).
CX is an Aspect-Oriented Network Interchange Format encoded in JSON,
which is used as basis for the R implementation of the CX format, namely RCX.
The RCX data model is implemented in the corresponding RCX to handle the networks.
8 Example Workflow
This example workflow shows how to connect to the public NDEx server, browse and retrieve the pathways of the Pathway Interaction Database of the NCI which are hosted there.
## load the library!
library(ndexr)
## login to the NDEx server
ndexcon <- ndex_connect()
## retrieve pathways of user 'nci-pid'
networks_pid <- ndex_find_networks(ndexcon, accountName = "nci-pid")
## list retrieved network information (only the first 10 entries)
networks_pid[1:10, "name"]## [1] "Syndecan-4-mediated signaling events (v2.0)"
## [2] "Syndecan-3-mediated signaling events (v2.0)"
## [3] "ErbB1 downstream signaling (v2.0)"
## [4] "Syndecan-2-mediated signaling events (v2.0)"
## [5] "ErbB receptor signaling network (v2.0)"
## [6] "Syndecan-1-mediated signaling events (v2.0)"
## [7] "EPO signaling pathway (v2.0)"
## [8] "Ephrin B reverse signaling (v2.0)"
## [9] "Sumoylation by RanBP2 regulates transcriptional repression (v2.0)"
## [10] "EPHB forward signaling (v2.0)"## show information on the first pathways listed
networks_pid[1, ]## ownerUUID isReadOnly subnetworkIds isValid
## 1 301a91c6-a37b-11e4-bda0-000c29202374 TRUE NULL TRUE
## warnings isShowcase isCertified indexLevel hasLayout hasSample cxFileSize
## 1 NULL FALSE FALSE ALL TRUE FALSE 205900
## cx2FileSize name
## 1 173363 Syndecan-4-mediated signaling events (v2.0)
## properties
## 1 NA, <p>Pillich RT, Chen J, Churas C, Fong D, Gyori BM, Ideker T, Karis K, Liu SN, Ono K, Pico A, Pratt D.<br/><b>NDEx IQuery: a multi-method network gene set analysis leveraging the Network Data Exchange</b>.<br/> Bioinformatics. 2023 Mar 1;39(3):btad118.<br/><a href="https://doi/org/10.1093/bioinformatics/btad118">doi: 10.1093/bioinformatics/btad118</a></p>, reference, string
## owner version completed
## 1 nci-pid 2.0 (20220901) TRUE
## description
## 1 <p>This is the updated version of an original NCI Pathway Interaction Database (PID) network.</p><p>The list of entities (genes, proteins, chemicals, etc) from the original network was used to query the <a href="https://www.indra.bio" target="_blank"><b>INDRA</b></a> database, retrieving high-quality relationships between entities. INDRA is a database that integrates information from multiple high-quality text mining engines, pathway databases, and small molecule resources. The INDRA-derived relationships are up-to-date and have links to detailed summaries of supporting literature evidence, including the specific supporting text.</p><p>While we have included only high-confidence relationships, text-mining complicated sentences can produce errors such as the reversal of up-regulation vs. down-regulation or the direction of an edge (i.e. B activates A instead of A activates B). Nevertheless, the entity recognition by the text miners is excellent and the text supporting a relationship almost always describes a genuine relationship between the entities.</p><p><b>Legend:</b><br/>BLUE: edges annotated by INDRA only.<br/>RED: edges annotated both by INDRA and PID.<br/>YELLOW: selected element.</p>
## visibility nodeCount edgeCount creationTime
## 1 PUBLIC 30 173 1.6651e+12
## externalId modificationTime isDeleted
## 1 00104179-45d1-11ed-b7d0-0ac135e8bacf 1.71813e+12 FALSE## retrieve network data
mynetwork <- ndex_get_network(ndexcon, networks_pid[1, "externalId"])
## visualize the network with RCX
RCX::visualize(mynetwork)
This code snippet starts with loading the ndexr library and connecting to the server anonymously.
Afterwards ndex_find_networks retrieves a list of networks of user nci-pid, which contains the data of the Pathway Interaction Database. The function ndex_get_network downloads the network data and stores in the RCX format and is then converted into an igraph object via RCX::toIgraph.
Here, the node IDs of the graph are set to readable names and the graph is plotted. Naturally, this graph can be annotated and beautified as required for the specific use cases.
9 Aspects and Metadata
In general it is not advisable to retrieve a complete RCX object from a server without knowing the number of aspects and its corresponding size, because this may cause unwanted or unnecessary network traffic and decline in performance. To avoid these problems, a possible workflow is to download the meta-data of a network at first to check the available aspects.
## get meta-data for a network
metadata <- ndex_network_get_metadata(ndexcon, networkId)
names(metadata)## [1] "name" "elementCount" "version" "idCounter"metadata[c("name", "elementCount")]## name elementCount
## 1 nodeAttributes 287
## 2 cyTableColumn 16
## 3 edges 215
## 4 cyVisualProperties 3
## 5 cyHiddenAttributes 3
## 6 nodes 146
## 7 networkAttributes 5
## 8 cartesianLayout 146
## 9 edgeAttributes 595Afterwards, only the favored aspects can be downloaded individually.
## get aspect 'nodeCitations' for the network
networkAttibutes <- ndex_network_get_aspect(ndexcon, networkId, "networkAttributes")
networkAttibutes## Network attributes:
## name
## 1 name
## 2 description
## 3 version
## 4 labels
## 5 @context
## value
## 1 BNFO 286 (Homework) - Direct p53 effectors example
## 2 Example network for Homework assignment in MED283/BNFO286 class.
## 3 1.0
## 4 3x BCL2L2
## 5 {"pubmed": "http://identifiers.org/pubmed/", "chebi": "http://identifiers.org/chebi/CHEBI:", "uniprot": "http://identifiers.org/uniprot/", "cas": "http://identifiers.org/cas/", "kegg.compound": "http://identifiers.org/kegg.compound/", "hprd": "http://identifiers.org/hprd/", "hgnc.symbol": "http://identifiers.org/hgnc.symbol/"}
## dataType isList
## 1 string FALSE
## 2 string FALSE
## 3 string FALSE
## 4 string FALSE
## 5 string FALSE10 NDEx Network properties
Even after creation, it is possible to change the name, the description or version of a network.
ndex_network_update_profile(ndexcon, networkId, name = "My network", version = "1.3")
ndex_network_update_profile(ndexcon, networkId, description = "Nothing to see here")For collaborative work, it is necessary to share networks between several users and groups. Therefore there are specialized functions to grant access to a network, change the permissions and withdraw access permissions. It is possible to use those functions on single users or groups. Possible permissions are “READ” to have reading access to private networks, “WRITE” to be able modify, and “ADMIN” for the owner of the network.
## show all user who have permission to a network
ndex_network_get_permission(ndexcon, networkId, "user")
## show all groups who have permission to a network
ndex_network_get_permission(ndexcon, networkId, "group")
## show all users with write access to a network
ndex_network_get_permission(ndexcon, networkId, "user", "WRITE")
## grant an user permission to a network
ndex_network_update_permission(ndexcon, networkId, user = someUserUuid, "READ")
## change the permission of an user to the network
ndex_network_update_permission(ndexcon, networkId, user = someUserUuid, "WRITE")
## withdraw the permission from an user
ndex_network_delete_permission(ndexcon, networkId, user = someUserUuid)Besides permission management on user and group level, it is also possible to set some system properties on a network that influence the accessibility further. By default a network is private, which means that it is only visible to the owner and invited users and groups. If at some point one decides to make the network readable by anyone, it is possible to change the visibility of a network to “PUBLIC”.
ndex_network_set_systemProperties(ndexcon, networkId, visibility = "PUBLIC")
ndex_network_set_systemProperties(ndexcon, networkId, visibility = "PRIVATE")When a network has reached the point to be published, further edits should be prevented. While it would be possible to set the access permissions of all users and groups to “READ”, this approach is very inconvenient. Therefore, a simpler way is to just set the network to read-only using the network system properties.
ndex_network_set_systemProperties(ndexcon, networkId, readOnly = TRUE)One also has the option at the NDEx server to choose a selection of their favorite networks for display in his or her home page.
ndex_network_set_systemProperties(ndexcon, networkId, showcase = TRUE)
ndex_network_set_systemProperties(ndexcon, networkId, showcase = FALSE)
# change more than one property simultaneously
ndex_network_set_systemProperties(
ndexcon, networkId, readOnly = TRUE, visibility = "PUBLIC", showcase = TRUE
)The provenance history aspect is now deprecated within the CX specification! The following description is left here for completeness and compatibility with old network specification!
The provenance history aspect of an NDEx network is used to document the workflow of events and information sources that produced the current network (for the official provenance documentation see http://www.home.ndexbio.org/network-provenance-history/ ). There is a convenience function, that retrieves the provenance of the network.
provenance <- ndex_network_get_provenance(ndexcon, networkId)11 API Compatibility with NDEx versions
In the following table all API functions are listed. The functions are grouped by the content they access, namely networks, users, or groups. For every function also is shown, if authentication is needed, and by which version it is supported (Version 2.0 or 1.3). A function marked with brackets indicates, that, although the function would be supported by this version, for different reasons no function could be implemented. Limitations of the single API functions are also given in the column of the corresponding version.
| Function name | Authentication | Version 2.x | Version 1.3 |
| Networks | |||
| ndex_find_networks | no | X | X |
| ndex_network_get_summary | no | X | X |
| ndex_get_network | no | X | X |
| ndex_create_network | yes | X | X |
| ndex_update_network | yes | X | X |
| ndex_delete_network | yes | X | X |
| ndex_network_get_metadata | no | X | (x) |
| ndex_network_aspect_get_metadata | no | (x) | |
| ndex_network_get_aspect | no | X | (x) |
| ndex_network_update_aspect | yes | (x) | |
| ndex_network_get_permission | yes | X | only for users, different response |
| ndex_network_update_permission | yes | X | (only for users) |
| ndex_network_delete_permission | yes | X | only for users |
| ndex_network_set_systemProperties | yes | X | only readOnly |
| ndex_network_update_profile | yes | X | X |
| ndex_network_get_provenance | no | (x) | X |
| Users | |||
| ndex_find_users | no | X | X |
| ndex_find_user_byName | no | X | |
| ndex_find_user_byId | no | X | |
| ndex_create_user | yes | X | |
| ndex_delete_user | yes | X | |
| ndex_update_user | yes | X | |
| ndex_verify_user | no | X | |
| ndex_user_change_password | yes | X | |
| ndex_user_mail_password | no | X | |
| ndex_user_forgot_password | no | X | |
| ndex_user_list_groups | yes | X | |
| ndex_user_show_group | yes | X | |
| ndex_user_list_permissions | yes | X | |
| ndex_user_show_permission | yes | X | |
| ndex_user_get_showcase | no | X | |
| ndex_user_get_networksummary | yes | X | |
| Groups | |||
| ndex_find_groups | no | X | X |
| ndex_get_group | no | X | |
| ndex_create_group | yes | X | |
| ndex_delete_group | yes | X | |
| ndex_update_group | yes | X | |
| ndex_group_list_users | no | X | |
| ndex_group_set_membership | yes | X | |
| ndex_group_list_networks | no | X | |
| ndex_group_network_get_permission | no | X |
12 Server REST API configuration
In the section “Connect to a server”, briefly a method for manually changing the API version was introduced, with the API definition stored in ndex_config.
names(ndex_config)## [1] "defaultVersion" "Version_2.1" "Version_2.0" "Version_1.3"str(ndex_config, max.level = 3)## List of 4
## $ defaultVersion: chr "Version_2.1"
## $ Version_2.1 :List of 3
## ..$ version : chr "2.1"
## ..$ connection:List of 3
## .. ..$ description: chr "URL of the NDEx server"
## .. ..$ host : chr "http://www.ndexbio.org"
## .. ..$ api : chr "/v2"
## ..$ api :List of 5
## .. ..$ serverStatus:List of 4
## .. ..$ user :List of 11
## .. ..$ group :List of 6
## .. ..$ network :List of 12
## .. ..$ search :List of 3
## $ Version_2.0 :List of 3
## ..$ version : chr "2.0"
## ..$ connection:List of 3
## .. ..$ description: chr "URL of the NDEx server"
## .. ..$ host : chr "http://www.ndexbio.org"
## .. ..$ api : chr "/v2"
## ..$ api :List of 5
## .. ..$ serverStatus:List of 3
## .. ..$ user :List of 11
## .. ..$ group :List of 6
## .. ..$ network :List of 12
## .. ..$ search :List of 3
## $ Version_1.3 :List of 3
## ..$ version : chr "1.3"
## ..$ connection:List of 3
## .. ..$ description: chr "URL of the NDEx server"
## .. ..$ host : chr "http://www.ndexbio.org"
## .. ..$ api : chr "/rest"
## ..$ api :List of 4
## .. ..$ serverStatus:List of 3
## .. ..$ user :List of 1
## .. ..$ network :List of 11
## .. ..$ search :List of 3This object contains the api definition for several versions (currently
version 1.3 and 2.0). By default, ndex_connect() uses the version defined
in ndex_config$defaultVersion (“Version_2.0”). To use another, or even a
customized version to establish a server connection, the ndexConf
parameter can be used, like shown before. In the following, the
structure of such a configuration is elaborated in more detail.
names(ndex_config$Version_2.0)## [1] "version" "connection" "api"The main structure of the configuration consists of three elements: The version is used to distinguish manually set configurations, which is used in some API functions to work differently for the single versions.
The “connection” element holds information about the default connection to the server, namely the host (e.g. “http://www.ndexbio.org/”) and the path to the api (e.g. “/v2” or “/rest”).
The REST API itself is defined in the “api” element, and follows the scheme of the function names, or the scheme of url paths likewise. E.g. in the “user” branch the different functions for handling user data are defined. If required, the functions might be grouped together in sub-branches furthermore. At the end of an branch, the actual definition of an API can be found.
To show, how such an API is defined and how to define one by themselves,
let’s have a look at
ndex_config$Version_2.0$api$user$password$mail, which is used by
ndex_user_mail_password(). Where to find the configuration of the
function is shown in the “REST query” section of the function
documentation. For a better readability, the yaml notation for this
function configuration is used:
mail:
description: "Causes a new password to be generated for ..."
url: "/user/#USERID#/password"
method: "PUT"
params:
user:
method: "replace"
tag: "#USERID#"
forgot:
method: "parameter"
tag: "forgot"
default: "true"Note: To get the yaml notation for the whole ndex_config simply use
yaml::as.yaml(ndex_config) (requires package yaml to be installed).
The single parameter definitions are given as list by the “params” parameter. Each parameter is defined by a method, and, if applicable, a tag, a default value and/or an optional flag. There are three keywords defining the method: replace, append or parameter.
- replace: The String defined by “tag” can be found within the url and
will be replaced by the given value of the parameter. E.g. the tag
#NETWORKID#in the url/network/#NETWORKID#/provenanceis replaced by a value (e.g.aaaaaaaa-bbbb-cccc-dddd-eeeeeeeeeeee) given as network id, which leads to the url/network/aaaaaaaa-bbbb-cccc-dddd-eeeeeeeeeeee/provenance. - append: The given value of the parameter is appended to an url.
Therefore the order of the parameters in the params definition is
used. E.g. the url
/network/searchand the given values forstart = 0andsize = 100generates the following url:/network/search/0/100 - parameter: Encodes the given parameters as url parameter using the
specified tag as parameter descriptor. E.g. a parameter with the tag
usernameand the valueSomeNameis encoded in the url/useras follows:/user?username=SomeName
It is also possible to set parameter as optional (except for replace),
or define default values. Values are assigned to the parameters using
the parameter name in the … parameter of the ndex_helper_encodeParams()
function. Parameters, that are not defined in the configuration are
ignored.
The easiest to write an own configuration is by simply copying an existing configuration and tailor it to the needs.
# Copy an existing config
custom_ndex_config <- ndex_config$Version_2.0
# Change the host connection for a local NDEx server installation
custom_ndex_config$connection$host <- "localhost:8090"
# Custom path to the REST api
custom_ndex_config$connection$api <- "/api/rest"
# Change the REST path for the ndex_get_network function
custom_ndex_config$api$network$get$url <- "/custom/networks/#NETWORKID#"
# Add some (default) parameters to the function
custom_ndex_config$api$network$get$params$newParam <- list(method = "parameter", tag = "someTag", default = "someValue")It is also possible to write an own configuration in yaml (or convert
ndex_config to yaml, see above) and load it as object (yaml::load or
yaml::load_file) or to translate the configuration into R code using
the function ndexr:::yamlToRConfig()
Note: For package maintenance it is advised to add new versions as yaml
definitions in /R/ndex_api_config.yml (for example as "Version_3.0") and update the R code in /R/ndex_api_config.r, which defines the ndex_config object.
yamlToRConfig <- function(
yamlFile = "R/ndex_api_config.yml", rScriptFile = "R/ndex_api_config.r",
defaultHeader = ndex_conf_header
) {
yamlObj <- yaml::yaml.load_file(yamlFile)
rCodeTxt <- paste0(defaultHeader, listToRCode(yamlObj))
outFile <- file(rScriptFile)
writeLines(rCodeTxt, outFile)
close(outFile)
}
yamlToRConfig()