title: Homology to peptide pattern for annotation of carbohydrate-active enzymes and prediction of function.
abstract: BACKGROUND
  Carbohydrate-active enzymes are found in all organisms and participate in key biological processes. These enzymes are classified in 274 families in the CAZy database but the sequence diversity within each family makes it a major task to identify new family members and to provide basis for prediction of enzyme function. A fast and reliable method for de novo annotation of genes encoding carbohydrate-active enzymes is to identify conserved peptides in the curated enzyme families followed by matching of the conserved peptides to the sequence of interest as demonstrated for the glycosyl hydrolase and the lytic polysaccharide monooxygenase families. This approach not only assigns the enzymes to families but also provides functional prediction of the enzymes with high accuracy.
  
  
  RESULTS
  We identified conserved peptides for all enzyme families in the CAZy database with Peptide Pattern Recognition. The conserved peptides were matched to protein sequence for de novo annotation and functional prediction of carbohydrate-active enzymes with the Hotpep method. Annotation of protein sequences from 12 bacterial and 16 fungal genomes to families with Hotpep had an accuracy of 0.84 (measured as F1-score) compared to semiautomatic annotation by the CAZy database whereas the dbCAN HMM-based method had an accuracy of 0.77 with optimized parameters. Furthermore, Hotpep provided a functional prediction with 86% accuracy for the annotated genes. Hotpep is available as a stand-alone application for MS Windows.
  
  
  CONCLUSIONS
  Hotpep is a state-of-the-art method for automatic annotation and functional prediction of carbohydrate-active enzymes.
authors.affiliation: Department of Chemical and Biochemical Engineering, Technical University of Denmark, Søltofts Plads, Building 229, 2800, Kgs. Lyngby, Denmark. pbus@kt.dtu.dk.
authors.forename: P K
authors.identifier: http://orcid.org/0000-0003-1920-636X
authors.initials: PK
authors.lastname: Busk
authors.affiliation: Department of Chemical and Biochemical Engineering, Technical University of Denmark, Søltofts Plads, Building 229, 2800, Kgs. Lyngby, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Pilgaard
authors.affiliation: Department of Chemical and Biochemical Engineering, Technical University of Denmark, Søltofts Plads, Building 229, 2800, Kgs. Lyngby, Denmark.
authors.forename: M J
authors.initials: MJ
authors.lastname: Lezyk
authors.affiliation: Department of Chemical and Biochemical Engineering, Technical University of Denmark, Søltofts Plads, Building 229, 2800, Kgs. Lyngby, Denmark.
authors.forename: A S
authors.initials: AS
authors.lastname: Meyer
authors.affiliation: Department of Chemical and Biochemical Engineering, Technical University of Denmark, Søltofts Plads, Building 229, 2800, Kgs. Lyngby, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Lange
mesh_terms: D001419:Bacteria / Q000145:classification / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D050260:Carbohydrate Metabolism; D030562:Databases, Protein; D004783:Environmental Microbiology; D005658:Fungi / Q000145:classification* / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D016680:Genome, Bacterial; D016681:Genome, Fungal; D006026:Glycoside Hydrolases / Q000737:chemistry / Q000235:genetics*; D006899:Mixed Function Oxygenases / Q000737:chemistry / Q000235:genetics*; D058977:Molecular Sequence Annotation
chemical_list: D006899:Mixed Function Oxygenases; D006026:Glycoside Hydrolases
keywords: Annotation; Carbohydrate-active enzymes; Genomics; Software