Interaction networks with StringDB
Last updated on 2025-12-02 | Edit this page
Estimated time: 12 minutes
Overview
Questions
- How can we use
STRINGdbto visualise protein–protein interaction networks for our DE genes? - How do we map our gene identifiers to the IDs used by STRING?
- What information does STRING functional enrichment add beyond standard GO/KEGG analysis?
Objectives
- Load and initialise the
STRINGdbobject for mouse. - Map a set of differentially expressed genes to STRING
identifiers.
- Visualise a protein–protein interaction network for top DE
genes.
- Retrieve and inspect STRING functional enrichment results.
Interaction networks with StringDB
So far, we have focused on pathway-level enrichment. Another useful way to interpret RNA-seq results is to look at protein–protein interaction (PPI) networks: Are our differentially expressed genes part of the same complexes or signalling modules?
The STRINGdb package provides an interface to the STRING database, which aggregates known and predicted PPIs from multiple sources (experiments, databases, text-mining, etc.).
In this lesson we will:
- Initialise a STRINGdb object for mouse.
- Map our top differentially expressed genes to STRING IDs.
- Plot an interaction network.
- Retrieve functional enrichment results from STRING.
R
# Initialize STRINGdb for mouse (taxonomy ID: 10090)
string_db <- STRINGdb$new(version = "12", species = 10090, score_threshold = 400, input_directory = "")
# Prepare data: select top 200 DE genes (by adjusted P value)
top200 <- debasal[order(debasal$adj.P.Val), ][1:200, ]
top200_mapped <- string_db$map(top200, "ENTREZID", removeUnmappedRows = TRUE)
OUTPUT
Warning: we couldn't map to STRING 2% of your identifiersR
# Plot the protein interaction network
string_db$plot_network(top200_mapped$STRING_id)
R
# Get functional enrichment (GO, KEGG, Reactome)
enrichment <- string_db$get_enrichment(top200_mapped$STRING_id)
head(enrichment)
OUTPUT
category term number_of_genes number_of_genes_in_background
1 COMPARTMENTS GOCC:0005730 22 442
2 COMPARTMENTS GOCC:0110165 151 13279
3 COMPARTMENTS GOCC:0030684 7 56
4 COMPARTMENTS GOCC:0031981 35 1642
5 COMPARTMENTS GOCC:0043229 113 8917
6 COMPARTMENTS GOCC:0043232 56 3336
ncbiTaxonId
1 10090
2 10090
3 10090
4 10090
5 10090
6 10090
inputGenes
1 10090.ENSMUSP00000000080,10090.ENSMUSP00000021048,10090.ENSMUSP00000021592,10090.ENSMUSP00000026999,10090.ENSMUSP00000037613,10090.ENSMUSP00000038580,10090.ENSMUSP00000039027,10090.ENSMUSP00000039853,10090.ENSMUSP00000042691,10090.ENSMUSP00000044653,10090.ENSMUSP00000044827,10090.ENSMUSP00000048337,10090.ENSMUSP00000048377,10090.ENSMUSP00000057984,10090.ENSMUSP00000067579,10090.ENSMUSP00000080085,10090.ENSMUSP00000081133,10090.ENSMUSP00000104167,10090.ENSMUSP00000116252,10090.ENSMUSP00000117461,10090.ENSMUSP00000120014,10090.ENSMUSP00000152412
2 10090.ENSMUSP00000000080,10090.ENSMUSP00000000199,10090.ENSMUSP00000000312,10090.ENSMUSP00000000769,10090.ENSMUSP00000001147,10090.ENSMUSP00000001181,10090.ENSMUSP00000001920,10090.ENSMUSP00000002152,10090.ENSMUSP00000004203,10090.ENSMUSP00000004646,10090.ENSMUSP00000007317,10090.ENSMUSP00000008036,10090.ENSMUSP00000014640,10090.ENSMUSP00000014743,10090.ENSMUSP00000019701,10090.ENSMUSP00000020308,10090.ENSMUSP00000020439,10090.ENSMUSP00000020524,10090.ENSMUSP00000020575,10090.ENSMUSP00000021048,10090.ENSMUSP00000021592,10090.ENSMUSP00000021617,10090.ENSMUSP00000021794,10090.ENSMUSP00000022176,10090.ENSMUSP00000022446,10090.ENSMUSP00000023807,10090.ENSMUSP00000023918,10090.ENSMUSP00000025236,10090.ENSMUSP00000025288,10090.ENSMUSP00000025639,10090.ENSMUSP00000025681,10090.ENSMUSP00000026076,10090.ENSMUSP00000026414,10090.ENSMUSP00000026999,10090.ENSMUSP00000027217,10090.ENSMUSP00000027941,10090.ENSMUSP00000028148,10090.ENSMUSP00000029194,10090.ENSMUSP00000029454,10090.ENSMUSP00000029482,10090.ENSMUSP00000029623,10090.ENSMUSP00000029625,10090.ENSMUSP00000029865,10090.ENSMUSP00000032386,10090.ENSMUSP00000032568,10090.ENSMUSP00000033054,10090.ENSMUSP00000033372,10090.ENSMUSP00000033386,10090.ENSMUSP00000034197,10090.ENSMUSP00000034457,10090.ENSMUSP00000034618,10090.ENSMUSP00000034650,10090.ENSMUSP00000034713,10090.ENSMUSP00000035105,10090.ENSMUSP00000036285,10090.ENSMUSP00000037613,10090.ENSMUSP00000037627,10090.ENSMUSP00000038017,10090.ENSMUSP00000038063,10090.ENSMUSP00000038580,10090.ENSMUSP00000038977,10090.ENSMUSP00000039027,10090.ENSMUSP00000039707,10090.ENSMUSP00000039853,10090.ENSMUSP00000040717,10090.ENSMUSP00000041175,10090.ENSMUSP00000041557,10090.ENSMUSP00000042691,10090.ENSMUSP00000044630,10090.ENSMUSP00000044653,10090.ENSMUSP00000044827,10090.ENSMUSP00000045036,10090.ENSMUSP00000045239,10090.ENSMUSP00000046755,10090.ENSMUSP00000047839,10090.ENSMUSP00000048334,10090.ENSMUSP00000048337,10090.ENSMUSP00000048377,10090.ENSMUSP00000050103,10090.ENSMUSP00000052020,10090.ENSMUSP00000053420,10090.ENSMUSP00000053962,10090.ENSMUSP00000056001,10090.ENSMUSP00000057096,10090.ENSMUSP00000057984,10090.ENSMUSP00000058042,10090.ENSMUSP00000058321,10090.ENSMUSP00000060202,10090.ENSMUSP00000062256,10090.ENSMUSP00000066857,10090.ENSMUSP00000067066,10090.ENSMUSP00000067579,10090.ENSMUSP00000068479,10090.ENSMUSP00000069257,10090.ENSMUSP00000069505,10090.ENSMUSP00000070216,10090.ENSMUSP00000072352,10090.ENSMUSP00000074198,10090.ENSMUSP00000074340,10090.ENSMUSP00000075619,10090.ENSMUSP00000077466,10090.ENSMUSP00000077612,10090.ENSMUSP00000078336,10090.ENSMUSP00000080085,10090.ENSMUSP00000080579,10090.ENSMUSP00000080717,10090.ENSMUSP00000081133,10090.ENSMUSP00000081712,10090.ENSMUSP00000084461,10090.ENSMUSP00000084977,10090.ENSMUSP00000086795,10090.ENSMUSP00000091799,10090.ENSMUSP00000092223,10090.ENSMUSP00000096728,10090.ENSMUSP00000097919,10090.ENSMUSP00000100013,10090.ENSMUSP00000101531,10090.ENSMUSP00000101696,10090.ENSMUSP00000102034,10090.ENSMUSP00000103048,10090.ENSMUSP00000104167,10090.ENSMUSP00000105312,10090.ENSMUSP00000105491,10090.ENSMUSP00000105743,10090.ENSMUSP00000106963,10090.ENSMUSP00000108726,10090.ENSMUSP00000112314,10090.ENSMUSP00000112923,10090.ENSMUSP00000113424,10090.ENSMUSP00000115871,10090.ENSMUSP00000115883,10090.ENSMUSP00000116252,10090.ENSMUSP00000117461,10090.ENSMUSP00000119242,10090.ENSMUSP00000120014,10090.ENSMUSP00000120085,10090.ENSMUSP00000121346,10090.ENSMUSP00000122733,10090.ENSMUSP00000122881,10090.ENSMUSP00000123590,10090.ENSMUSP00000124565,10090.ENSMUSP00000125531,10090.ENSMUSP00000126448,10090.ENSMUSP00000132519,10090.ENSMUSP00000133478,10090.ENSMUSP00000135040,10090.ENSMUSP00000140275,10090.ENSMUSP00000141104,10090.ENSMUSP00000142770,10090.ENSMUSP00000144979,10090.ENSMUSP00000152412
3 10090.ENSMUSP00000001339,10090.ENSMUSP00000037613,10090.ENSMUSP00000038580,10090.ENSMUSP00000039027,10090.ENSMUSP00000048377,10090.ENSMUSP00000080085,10090.ENSMUSP00000152412
4 10090.ENSMUSP00000000080,10090.ENSMUSP00000014640,10090.ENSMUSP00000014743,10090.ENSMUSP00000021048,10090.ENSMUSP00000021592,10090.ENSMUSP00000022446,10090.ENSMUSP00000026999,10090.ENSMUSP00000027941,10090.ENSMUSP00000029194,10090.ENSMUSP00000037613,10090.ENSMUSP00000038580,10090.ENSMUSP00000039027,10090.ENSMUSP00000039853,10090.ENSMUSP00000042691,10090.ENSMUSP00000044653,10090.ENSMUSP00000044827,10090.ENSMUSP00000048337,10090.ENSMUSP00000048377,10090.ENSMUSP00000057984,10090.ENSMUSP00000067579,10090.ENSMUSP00000069505,10090.ENSMUSP00000080085,10090.ENSMUSP00000081133,10090.ENSMUSP00000084461,10090.ENSMUSP00000097919,10090.ENSMUSP00000100013,10090.ENSMUSP00000104167,10090.ENSMUSP00000105743,10090.ENSMUSP00000116252,10090.ENSMUSP00000117461,10090.ENSMUSP00000120014,10090.ENSMUSP00000121346,10090.ENSMUSP00000124565,10090.ENSMUSP00000133478,10090.ENSMUSP00000152412
5 10090.ENSMUSP00000000080,10090.ENSMUSP00000000199,10090.ENSMUSP00000000312,10090.ENSMUSP00000001920,10090.ENSMUSP00000002152,10090.ENSMUSP00000004203,10090.ENSMUSP00000004646,10090.ENSMUSP00000007317,10090.ENSMUSP00000008036,10090.ENSMUSP00000014640,10090.ENSMUSP00000014743,10090.ENSMUSP00000020308,10090.ENSMUSP00000020524,10090.ENSMUSP00000021048,10090.ENSMUSP00000021592,10090.ENSMUSP00000021617,10090.ENSMUSP00000021794,10090.ENSMUSP00000022176,10090.ENSMUSP00000022446,10090.ENSMUSP00000023918,10090.ENSMUSP00000025236,10090.ENSMUSP00000025288,10090.ENSMUSP00000025639,10090.ENSMUSP00000025681,10090.ENSMUSP00000026999,10090.ENSMUSP00000027217,10090.ENSMUSP00000027941,10090.ENSMUSP00000028148,10090.ENSMUSP00000029194,10090.ENSMUSP00000029454,10090.ENSMUSP00000029482,10090.ENSMUSP00000029623,10090.ENSMUSP00000029865,10090.ENSMUSP00000032386,10090.ENSMUSP00000032568,10090.ENSMUSP00000033372,10090.ENSMUSP00000034197,10090.ENSMUSP00000034713,10090.ENSMUSP00000035105,10090.ENSMUSP00000036285,10090.ENSMUSP00000037613,10090.ENSMUSP00000037627,10090.ENSMUSP00000038017,10090.ENSMUSP00000038063,10090.ENSMUSP00000038580,10090.ENSMUSP00000039027,10090.ENSMUSP00000039707,10090.ENSMUSP00000039853,10090.ENSMUSP00000040717,10090.ENSMUSP00000041175,10090.ENSMUSP00000042691,10090.ENSMUSP00000044630,10090.ENSMUSP00000044653,10090.ENSMUSP00000044827,10090.ENSMUSP00000045239,10090.ENSMUSP00000048337,10090.ENSMUSP00000048377,10090.ENSMUSP00000050103,10090.ENSMUSP00000052020,10090.ENSMUSP00000053962,10090.ENSMUSP00000056001,10090.ENSMUSP00000057984,10090.ENSMUSP00000058042,10090.ENSMUSP00000058321,10090.ENSMUSP00000062256,10090.ENSMUSP00000067579,10090.ENSMUSP00000068479,10090.ENSMUSP00000069257,10090.ENSMUSP00000069505,10090.ENSMUSP00000070216,10090.ENSMUSP00000074198,10090.ENSMUSP00000075619,10090.ENSMUSP00000077466,10090.ENSMUSP00000077612,10090.ENSMUSP00000078336,10090.ENSMUSP00000080085,10090.ENSMUSP00000080579,10090.ENSMUSP00000080717,10090.ENSMUSP00000081133,10090.ENSMUSP00000081712,10090.ENSMUSP00000084461,10090.ENSMUSP00000084977,10090.ENSMUSP00000092223,10090.ENSMUSP00000096728,10090.ENSMUSP00000097919,10090.ENSMUSP00000100013,10090.ENSMUSP00000102034,10090.ENSMUSP00000103048,10090.ENSMUSP00000104167,10090.ENSMUSP00000105312,10090.ENSMUSP00000105491,10090.ENSMUSP00000105743,10090.ENSMUSP00000106963,10090.ENSMUSP00000108726,10090.ENSMUSP00000112314,10090.ENSMUSP00000112923,10090.ENSMUSP00000115871,10090.ENSMUSP00000115883,10090.ENSMUSP00000116252,10090.ENSMUSP00000117461,10090.ENSMUSP00000120014,10090.ENSMUSP00000120085,10090.ENSMUSP00000121346,10090.ENSMUSP00000122733,10090.ENSMUSP00000123590,10090.ENSMUSP00000124565,10090.ENSMUSP00000126448,10090.ENSMUSP00000133478,10090.ENSMUSP00000135040,10090.ENSMUSP00000140275,10090.ENSMUSP00000142770,10090.ENSMUSP00000144979,10090.ENSMUSP00000152412
6 10090.ENSMUSP00000000080,10090.ENSMUSP00000000312,10090.ENSMUSP00000001920,10090.ENSMUSP00000004646,10090.ENSMUSP00000007317,10090.ENSMUSP00000008036,10090.ENSMUSP00000021048,10090.ENSMUSP00000021592,10090.ENSMUSP00000021617,10090.ENSMUSP00000021794,10090.ENSMUSP00000025681,10090.ENSMUSP00000026999,10090.ENSMUSP00000027941,10090.ENSMUSP00000029454,10090.ENSMUSP00000029482,10090.ENSMUSP00000033372,10090.ENSMUSP00000035105,10090.ENSMUSP00000037613,10090.ENSMUSP00000038580,10090.ENSMUSP00000039027,10090.ENSMUSP00000039707,10090.ENSMUSP00000039853,10090.ENSMUSP00000042691,10090.ENSMUSP00000044653,10090.ENSMUSP00000044827,10090.ENSMUSP00000048337,10090.ENSMUSP00000048377,10090.ENSMUSP00000052020,10090.ENSMUSP00000057984,10090.ENSMUSP00000067579,10090.ENSMUSP00000068479,10090.ENSMUSP00000069257,10090.ENSMUSP00000069505,10090.ENSMUSP00000074198,10090.ENSMUSP00000078336,10090.ENSMUSP00000080085,10090.ENSMUSP00000080579,10090.ENSMUSP00000081133,10090.ENSMUSP00000084461,10090.ENSMUSP00000092223,10090.ENSMUSP00000097919,10090.ENSMUSP00000102034,10090.ENSMUSP00000104167,10090.ENSMUSP00000105312,10090.ENSMUSP00000105491,10090.ENSMUSP00000115871,10090.ENSMUSP00000116252,10090.ENSMUSP00000117461,10090.ENSMUSP00000120014,10090.ENSMUSP00000120085,10090.ENSMUSP00000122733,10090.ENSMUSP00000123590,10090.ENSMUSP00000124565,10090.ENSMUSP00000133478,10090.ENSMUSP00000135040,10090.ENSMUSP00000152412
preferredNames
1 Klf6,Ftsj3,Cdca7l,Smad7,Fbl,Rrp9,Tsr1,Rrp12,Ddx21,Cd3eap,Mybbp1a,Wdr43,Utp4,Riox1,Rcl1,Rrp1b,Nol9,Dhx33,Grwd1,Rpl12,Nhp2,Gtpbp4
2 Klf6,Ncs1,Cdh1,Serpinf1,Col6a1,Col6a2,Aif1l,Bbc3,Ppan,Coro1c,Krt19,Rplp1,Ankrd28,Csf1,Dusp9,Ddit4,Wif1,Rhbdf1,Fstl3,Ftsj3,Cdca7l,Asb2,Nedd9,Hmgcr,Eaf1,Igfbp6,Ivns1abp,Stard4,Zfp521,Ccdc86,Cdc42bpg,Gfra1,Dgka,Smad7,Ecrg4,Atf3,Fpgs,Skil,Casq2,Gpsm2,Tlr2,Sfrp2,Trp53inp1,Bhlhe41,Dmpk,Adm,Rp2,Mrgprf,St3gal2,Urb2,Pdzd3,Mcam,Ldlr,Rpsa,Smad6,Fbl,Trp53inp2,Tm6sf1,Dhcr24,Rrp9,Naa25,Tsr1,Micall2,Rrp12,Cox8a,Cyp2s1,Slc7a5,Ddx21,Lad1,Cd3eap,Mybbp1a,Myof,Golgb1,Gjb3,Ppp1r13l,Fbln2,Wdr43,Utp4,Rnf152,Flnb,Cldn4,Lcn2,Irgm2,Dsg2,Riox1,Rab11fip1,Cavin1,Uck2,Adrb2,Slit3,Lif,Rcl1,Ak1,Ppp1r12a,Nr1d1,Zfp46,Csn1s2b,Nfatc2,Hmcn1,Rabep1,Emp2,C1qbp,Ablim1,Rrp1b,Dysf,Chil1,Nol9,Dnajb5,Ppp1r10,Prune2,Lgals1,Cldn3,Map1a,Mafb,Mapt,Sox4,Gpr3,Gjb4,Synpo2,Aen,Dhx33,Triobp,Fam110a,Plcb1,Arhgap1,Naaa,Barx2,Mgst1,Adamtsl4,Slain2,Vegfa,Grwd1,Rpl12,Atp2b4,Nhp2,Cep350,Taf13,Tnni2,Mfsd6,Usp10,Alkbh1,C1s1,Acot1,Emp3,Baz1a,Tppp3,Kcnma1,Mybph,Fdps,Creb5,Gtpbp4
3 Rrp15,Fbl,Rrp9,Tsr1,Utp4,Rrp1b,Gtpbp4
4 Klf6,Ankrd28,Csf1,Ftsj3,Cdca7l,Eaf1,Smad7,Atf3,Skil,Fbl,Rrp9,Tsr1,Rrp12,Ddx21,Cd3eap,Mybbp1a,Wdr43,Utp4,Riox1,Rcl1,Nr1d1,Rrp1b,Nol9,Ppp1r10,Mapt,Sox4,Dhx33,Plcb1,Grwd1,Rpl12,Nhp2,Taf13,Alkbh1,Baz1a,Gtpbp4
5 Klf6,Ncs1,Cdh1,Aif1l,Bbc3,Ppan,Coro1c,Krt19,Rplp1,Ankrd28,Csf1,Ddit4,Rhbdf1,Ftsj3,Cdca7l,Asb2,Nedd9,Hmgcr,Eaf1,Ivns1abp,Stard4,Zfp521,Ccdc86,Cdc42bpg,Smad7,Ecrg4,Atf3,Fpgs,Skil,Casq2,Gpsm2,Tlr2,Trp53inp1,Bhlhe41,Dmpk,Rp2,St3gal2,Ldlr,Rpsa,Smad6,Fbl,Trp53inp2,Tm6sf1,Dhcr24,Rrp9,Tsr1,Micall2,Rrp12,Cox8a,Cyp2s1,Ddx21,Lad1,Cd3eap,Mybbp1a,Golgb1,Wdr43,Utp4,Rnf152,Flnb,Lcn2,Irgm2,Riox1,Rab11fip1,Cavin1,Adrb2,Rcl1,Ak1,Ppp1r12a,Nr1d1,Zfp46,Nfatc2,Rabep1,Emp2,C1qbp,Ablim1,Rrp1b,Dysf,Chil1,Nol9,Dnajb5,Ppp1r10,Prune2,Map1a,Mafb,Mapt,Sox4,Synpo2,Aen,Dhx33,Triobp,Fam110a,Plcb1,Arhgap1,Naaa,Barx2,Mgst1,Slain2,Vegfa,Grwd1,Rpl12,Nhp2,Cep350,Taf13,Tnni2,Usp10,Alkbh1,Acot1,Baz1a,Tppp3,Kcnma1,Fdps,Creb5,Gtpbp4
6 Klf6,Cdh1,Aif1l,Coro1c,Krt19,Rplp1,Ftsj3,Cdca7l,Asb2,Nedd9,Cdc42bpg,Smad7,Atf3,Casq2,Gpsm2,Rp2,Rpsa,Fbl,Rrp9,Tsr1,Micall2,Rrp12,Ddx21,Cd3eap,Mybbp1a,Wdr43,Utp4,Flnb,Riox1,Rcl1,Ak1,Ppp1r12a,Nr1d1,Nfatc2,Ablim1,Rrp1b,Dysf,Nol9,Ppp1r10,Map1a,Mapt,Synpo2,Dhx33,Triobp,Fam110a,Slain2,Grwd1,Rpl12,Nhp2,Cep350,Tnni2,Usp10,Alkbh1,Baz1a,Tppp3,Gtpbp4
p_value fdr description
1 1.73e-10 3.82e-07 Nucleolus
2 6.67e-07 7.40e-04 Cellular anatomical entity
3 1.39e-06 8.80e-04 Preribosome
4 1.63e-06 8.80e-04 Nuclear lumen
5 1.20e-06 8.80e-04 Intracellular organelle
6 1.50e-06 8.80e-04 Intracellular non-membrane-bounded organelleThere are many available ways of exploring your data using the STRING
database that can’t be covered in one tutorial but you can learn more by
reading the vignette
and inspect available functions within the STRINGdb package
by running:
R
STRINGdb$methods()
OUTPUT
[1] ".objectPackage" ".objectParent"
[3] "add_diff_exp_color" "add_proteins_description"
[5] "benchmark_ppi" "benchmark_ppi_pathway_view"
[7] "callSuper" "copy"
[9] "enrichment_heatmap" "export"
[11] "field" "get_aliases"
[13] "get_annotations" "get_bioc_graph"
[15] "get_clusters" "get_enrichment"
[17] "get_graph" "get_homologs"
[19] "get_homologs_besthits" "get_homology_graph"
[21] "get_interactions" "get_link"
[23] "get_neighbors" "get_paralogs"
[25] "get_pathways_benchmarking_blackList" "get_png"
[27] "get_ppi_enrichment" "get_ppi_enrichment_full"
[29] "get_proteins" "get_pubmed"
[31] "get_pubmed_interaction" "get_subnetwork"
[33] "get_summary" "get_term_proteins"
[35] "getClass" "getRefClass"
[37] "import" "initFields"
[39] "initialize" "load"
[41] "load_all" "map"
[43] "mp" "plot_network"
[45] "plot_ppi_enrichment" "post_payload"
[47] "ppi_enrichment" "remove_homologous_interactions"
[49] "set_background" "show"
[51] "show#envRefClass" "trace"
[53] "untrace" "usingMethods" Read more about STRING:
- Szklarczyk, Damian et al. “The STRING database in 2025: protein networks with directionality of regulation.” Nucleic acids research vol. 53,D1 (2025): D730-D737. doi:10.1093/nar/gkae1113
STRINGdblinks your genes to protein–protein interaction networks from the STRING database.Mapping from gene IDs (e.g. ENTREZ) to STRING IDs is a crucial first step.
Network visualisation can reveal modules of interconnected DE genes that may not be obvious from lists or tables.
STRING provides its own functional enrichment, which can complement results from
clusterProfilerandfgsea.