# Building PPIs from StringDB

Jonathan Ronen1 and Altuna Akalin1

1Berlin Institute for Medical Systems Biology, Max Delbrück Center

#### 2022-11-01

# 1 Introduction

This vignette demonstrates how a Protein-Protein interaction (PPI) graph may be constructed from the database stringDB.

# 2 Obtaining network data from stringDB

Other networks can also be used with netSmooth. We mostly rely on networks from stringDB. StringDB has multiple species available such as human, mouse, zebrafish, C.elengas and D.melanogaster. It is also possible to prune the network differently. For our purposes we use the edges that have highest confidence score. Below, we are showing how to obtain and prune human network from stringDB. Specifically, we use the work flow below.

1. Get human network/graph from STRINGdb.
2. Prune the network to get only high-confidence edges
3. Create adjacency matrix
4. Map protein ids in the network to Ensembl Gene ids in the adjacency matrix

    require(STRINGdb)
    require(igraph)
    require(biomaRt)

    # 1. getSTRINGdb for human
    string_db <- STRINGdb$new(species=9606)
    human_graph <- string_db$get_graph()

    # 2. get edges with high confidence score
    edge.scores <- E(human_graph)$combined_score
    ninetyth.percentile <- quantile(edge.scores, 0.9)
    thresh <- data.frame(name='90th percentile',
                         val=ninetyth.percentile)
    human_graph <- subgraph.edges(human_graph,
                                  E(human_graph)[combined_score > ninetyth.percentile])

    # 3. create adjacency matrix
    adj_matrix <- as_adjacency_matrix(human_graph)

    # 4. map gene ids to protein ids

    ### get gene/protein ids via Biomart
    mart=useMart(host = 'grch37.ensembl.org',
                 biomart='ENSEMBL_MART_ENSEMBL',
                 dataset='hsapiens_gene_ensembl')

    ### extract protein ids from the human network
    protein_ids <- sapply(strsplit(rownames(adj_matrix), '\\.'),
                          function(x) x[2])

    ### get protein to gene id mappings
    mart_results <- getBM(attributes = c("ensembl_gene_id",
                                         "ensembl_peptide_id"),
                          filters = "ensembl_peptide_id", values = protein_ids,
                          mart = mart)

    ### replace protein ids with gene ids
    ix <- match(protein_ids, mart_results$ensembl_peptide_id)
    ix <- ix[!is.na(ix)]

    newnames <- protein_ids
    newnames[match(mart_results[ix,'ensembl_peptide_id'], newnames)] <-
        mart_results[ix, 'ensembl_gene_id']
    rownames(adj_matrix) <- newnames
    colnames(adj_matrix) <- newnames

    ppi <- adj_matrix[!duplicated(newnames), !duplicated(newnames)]
    nullrows <- Matrix::rowSums(ppi)==0
    ppi <- ppi[!nullrows,!nullrows] ## ppi is the network with gene ids

    sessionInfo()

    ## R version 4.2.1 (2022-06-23 ucrt)
    ## Platform: x86_64-w64-mingw32/x64 (64-bit)
    ## Running under: Windows Server x64 (build 20348)
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    ## Matrix products: default
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    ## [4] LC_NUMERIC=C
    ## [5] LC_TIME=English_United States.utf8
    ##
    ## attached base packages:
    ## [1] stats     graphics  grDevices utils     datasets  methods   base
    ##
    ## other attached packages:
    ## [1] BiocStyle_2.26.0
    ##
    ## loaded via a namespace (and not attached):
    ##  [1] bookdown_0.29       digest_0.6.30       R6_2.5.1
    ##  [4] jsonlite_1.8.3      magrittr_2.0.3      evaluate_0.17
    ##  [7] stringi_1.7.8       cachem_1.0.6        rlang_1.0.6
    ## [10] cli_3.4.1           jquerylib_0.1.4     bslib_0.4.0
    ## [13] rmarkdown_2.17      tools_4.2.1         stringr_1.4.1
    ## [16] xfun_0.34           yaml_2.3.6          fastmap_1.1.0
    ## [19] compiler_4.2.1      BiocManager_1.30.19 htmltools_0.5.3
    ## [22] knitr_1.40          sass_0.4.2