EFI - Genome Neighborhood Tool

This web resource is supported by a Research Resource from the National Institute of General Medical Sciences (R24GM141196-01).

The tools are available without charge or license to both academic and commercial users.

Please cite your use of the EFI tools:

Rémi Zallot, Nils Oberg, and John A. Gerlt, The EFI Web Resource for Genomic Enzymology Tools: Leveraging Protein, Genome, and Metagenome Databases to Discover Novel Enzymes and Metabolic Pathways. Biochemistry 2019 58 (41), 4169-4182. https://doi.org/10.1021/acs.biochem.9b00735

Nils Oberg, Rémi Zallot, and John A. Gerlt, EFI-EST, EFI-GNT, and EFI-CGFP: Enzyme Function Initiative (EFI) Web Resource for Genomic Enzymology Tools. J Mol Biol 2023. https://doi.org/10.1016/j.jmb.2023.168018

Update of EFI Tools

The EFI Tools are being upgraded on 10/26/26. The site will not be available from 10/23-10/26 for maintenance.

While the updated site is functionally identical to the old site, jobs run prior to that date will only be available through the results link in the finalization email (not the Previous Jobs tab). User accounts created on the old site will no longer be available, and users are encouraged to create new accounts when the upgraded site becomes available.

EFI-GNT allows exploration of the genome neighborhoods for sequence similarity network (SSN) clusters in order to facilitate the assignment of function within protein families and superfamilies.

In GNT Submission, each sequence within a SSN is used as a query for interrogation of its genome neighborhood. A colored SSN identifying clusters, Genome Neighborhood Networks (GNNs) providing statistical analysis of neighboring Pfam families, Genome Neighborhood Diagrams (GNDs), sets of IDs and sequences per cluster and additional files are created. For the Retrieve Neighorhood Diagrams option, only GNDs will be created.

A listing of new features and other information pertaining to GNT is available on the release notes page.

The GNT database uses UniProt 2026_02, and ENA downloaded on June 2026.

GNT Submission
Retrieve Neighborhood Diagrams
View Saved Diagrams
Tutorial

Submission is currently disabled due to site maintenance.

Clicking on the headers below provides access to various ways of generating genomic neighborhood diagrams.

Single Sequence BLAST
Sequence ID Lookup
FASTA Sequence Lookup

Submission is currently disabled due to site maintenance.

EFI-Genome Neighborhood Tool Overview

The EFI-GNT (EFI Genome Neighborhood Tool) is focused on placing protein families and superfamilies into a genomic context. A sequence similarity network (SSN) is used as an input. Each sequence within a SSN is used as a query for interrogation of its genome neighborhood.

EFI-GNT enables exploration of the genome neighborhoods for sequences in SSN clusters in order to facilitate their assignment of function.

EFI-GNT Acceptable Input

EFI-GNT is compatible with SSN generated by the EFI-Enzyme Similarity Tool (EFI-EST). Acceptable SSNs are generated for an entire Pfam and/or InterPro protein family (EFI-EST option B), a focused region of a family (option A), a set of protein sequence that can be identified from FASTA headers (from option C with “Header Reading” activated) or a list of recognizable UniProt and/or NCBI IDs (from option D). SSNs manually modified within Cytoscape are accepted. SSNs that have been colored using the "Color SSN Utility" are also accepted. SSNs generated from FASTA sequences (option C) without the "Read Header" option activated are not accepted.

Principle of GNT Analysis

EFI-GNT provides statistical analysis, per SSN cluster, of genome context for bacterial, archeal and fungal sequences, in order to identify possible functional linkage. Sequences from the SSN analyzed are used as query for retrieval of their genome neighborhood. The user specifies the neighborhood size (±N orfs from the SSN query) and minimum query-neighbor co-occurrence frequency for the outputs.

EFI-GNT Output

EFI-GNT identifies each SSN cluster and assigns it a unique color. A colored SSN is produced. It then interrogates the European Nucleotide Archive (ENA; https://www.ebi.ac.uk/ena) to obtain the genome contexts of each sequence, sorts neighbors into Pfam families, and provides three specific outputs. Firstly, a GNN network in which each SSN cluster is a hub node with its spoke nodes identified neighboring Pfam families (for identifying candidates for pathway enzymes); secondly, a GNN network in which each neighbor Pfam family is a hub node with its spoke nodes that SSN clusters that identify this Pfam as a neighbor (for identifying divergent clusters that are orthologues); and thirdly, genome neighborhood diagrams (GNDs) for visual representations of the neighborhoods for the sequences in each SSN cluster (for visual inspection of synteny and the presence/absence of functionally linked proteins).

Direct Genomic Neighborhood Diagrams (GND) Generation

The "Retrieve neighborhood diagrams" allows exploring of neighboring genes for specific queries. You can submit a single sequence that is used as the query for a BLAST search of the UniProt database. The retrieved sequences are used to generate GNDs. GNDs can be generated from a provided list of IDs or even from FASTA sequences, by collecting IDs from FASTA headers.

Figure 1: Examples of colored SSN (left) and a hub-and-spoke cluster from a GNN (right).