This website contains a collection of webtools for creating and interacting with sequence similarity networks (SSNs) and genome neighborhood networks (GNNs). These tools originated in the Enzyme Function Initiative, a NIH-funded research project to develop a sequence / structure-based strategy for facilitating discovery of in vitro enzymatic and in vivo metabolic / physiological functions of unknown enzymes discovered in genome projects.
The Enzyme Function Initiative tools are hosted at the Carl R. Woese Institute for Genomic Biology (IGB), at the University of Illinois at Urbana-Champaign. The development of these tools is headed by John A. Gerlt (PI), aided by scientist Rémi Zallot and software engineers Dan Davidson, David Slater, and Nils Oberg. The computational infrastracture is supported by the Computer and Network Resource Group at IGB.
A "From The Bench" article was recently published in Biochemistry and is available on the training resources page.
The web tools have been described in four publications:
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
Rémi Zallot, Nils Oberg, John A. Gerlt, "Democratized" genomic enzymology web tools for functional assignment, Current Opinion in Chemical Biology, Volume 47, 2018, Pages 77-85, https://doi.org/10.1016/j.cbpa.2018.09.009
John A. Gerlt, Genomic enzymology: Web tools for leveraging protein family sequence–function space and genome context to discover novel functions, Biochemistry. Volume 56, 2017, Pages 4293-4308. https://doi.org/10.1021/acs.biochem.7b00614
John A. Gerlt, Jason T. Bouvier, Daniel B. Davidson, Heidi J. Imker, Boris Sadkhin, David R. Slater, Katie L. Whalen, Enzyme Function Initiative-Enzyme Similarity Tool (EFI-EST): A web tool for generating protein sequence similarity networks, Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Volume 1854, Issue 8, 2015, Pages 1019-1037, ISSN 1570-9639, https://dx.doi.org/10.1016/j.bbapap.2015.04.015
|SSN Creation SSN creation from sequences, Pfam or InterPro famil(ies), and UniProt and/or NCBI protein accession IDs.||GNN Creation GNN creation from sequence similarity networks.|
|Genome neighborhood diagrams Genome neighborhood diagrams from sequences, sequence IDs, or GNNs.||Functional Profiling Computationally-guided functional profiling using ShortBRED and the CGFP tools from the Balskus and Huttenhower Labs at Harvard University.|
These webtools use NCBI BLAST and CD-HIT to create SSNs and GNNs. The computationally-guided functional profiling tool uses the CGFP programs from the Balskus Lab (https://bitbucket.org/biobakery/cgfp/src) and ShortBRED from the Huttenhower Lab (http://huttenhower.sph.harvard.edu/shortbred). The data used originate from the UniProt Consortium databases and the InterPro and ENA databases from EMBL-EBI.
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