AGeNNT: annotation of enzyme families by means of refined neighborhood networksReport as inadecuate

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BMC Bioinformatics

, 18:274

Networks analysis


BackgroundLarge enzyme families may contain functionally diverse members that give rise to clusters in a sequence similarity network SSN. In prokaryotes, the genome neighborhood of a gene-product is indicative of its function and thus, a genome neighborhood network GNN deduced for an SSN provides strong clues to the specific function of enzymes constituting the different clusters. The Enzyme Function Initiative offers services that compute SSNs and GNNs.

ResultsWe have implemented AGeNNT that utilizes these services, albeit with datasets purged with respect to unspecific protein functions and overrepresented species. AGeNNT generates refined GNNs rGNNs that consist of cluster-nodes representing the sequences under study and Pfam-nodes representing enzyme functions encoded in the respective neighborhoods. For cluster-nodes, AGeNNT summarizes the phylogenetic relationships of the contributing species and a statistic indicates how unique nodes and GNs are within this rGNN. Pfam-nodes are annotated with additional features like GO terms describing protein function. For edges, the coverage is given, which is the relative number of neighborhoods containing the considered enzyme function Pfam-node. AGeNNT is available at

ConclusionsAn rGNN is easier to interpret than a conventional GNN, which commonly contains proteins without enzymatic function and overly specific neighborhoods due to phylogenetic bias. The implemented filter routines and the statistic allow the user to identify those neighborhoods that are most indicative of a specific metabolic capacity. Thus, AGeNNT facilitates to distinguish and annotate functionally different members of enzyme families.

KeywordsSequence similarity network SSN Genome neighborhood network GNN Genome content Enzyme function Homology-free annotation AbbreviationsEFIEnzyme Function Initiative

GNGenome neighborhood

GNNGenome neighborhood network

NCBINational Center for Biotechnology Information

PfamProtein family

rGNNrefined genome neighborhood network

SSNSequence similarity network


Electronic supplementary materialThe online version of this article doi:10.1186-s12859-017-1689-6 contains supplementary material, which is available to authorized users.

Author: Florian Kandlinger - Maximilian G. Plach - Rainer Merkl


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