title: CRISPRstrand: predicting repeat orientations to determine the crRNA-encoding strand at CRISPR loci.
abstract: BACKGROUND
  The discovery of CRISPR-Cas systems almost 20 years ago rapidly changed our perception of the bacterial and archaeal immune systems. CRISPR loci consist of several repetitive DNA sequences called repeats, inter-spaced by stretches of variable length sequences called spacers. This CRISPR array is transcribed and processed into multiple mature RNA species (crRNAs). A single crRNA is integrated into an interference complex, together with CRISPR-associated (Cas) proteins, to bind and degrade invading nucleic acids. Although existing bioinformatics tools can recognize CRISPR loci by their characteristic repeat-spacer architecture, they generally output CRISPR arrays of ambiguous orientation and thus do not determine the strand from which crRNAs are processed. Knowledge of the correct orientation is crucial for many tasks, including the classification of CRISPR conservation, the detection of leader regions, the identification of target sites (protospacers) on invading genetic elements and the characterization of protospacer-adjacent motifs.
  
  
  RESULTS
  We present a fast and accurate tool to determine the crRNA-encoding strand at CRISPR loci by predicting the correct orientation of repeats based on an advanced machine learning approach. Both the repeat sequence and mutation information were encoded and processed by an efficient graph kernel to learn higher-order correlations. The model was trained and tested on curated data comprising >4500 CRISPRs and yielded a remarkable performance of 0.95 AUC ROC (area under the curve of the receiver operator characteristic). In addition, we show that accurate orientation information greatly improved detection of conserved repeat sequence families and structure motifs. We integrated CRISPRstrand predictions into our CRISPRmap web server of CRISPR conservation and updated the latter to version 2.0.
  
  
  BACKGROUND
  CRISPRmap and CRISPRstrand are available at http://rna.informatik.uni-freiburg.de/CRISPRmap.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Department of Computer Science, University of Freiburg, Georges-Köhler-Allee 106, 79110 Freiburg, Germany, Department of Biology, University of Copenhagen, Archaea Centre, Ole Maaloes Vej 5, DK2200 Copenhagen, Denmark and BIOSS Centre for Biological Signalling Studies, Cluster of Excellence, University of Freiburg, Germany.
authors.forename: Omer S
authors.initials: OS
authors.lastname: Alkhnbashi
authors.affiliation: Department of Computer Science, University of Freiburg, Georges-Köhler-Allee 106, 79110 Freiburg, Germany, Department of Biology, University of Copenhagen, Archaea Centre, Ole Maaloes Vej 5, DK2200 Copenhagen, Denmark and BIOSS Centre for Biological Signalling Studies, Cluster of Excellence, University of Freiburg, Germany.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Costa
authors.affiliation: Department of Computer Science, University of Freiburg, Georges-Köhler-Allee 106, 79110 Freiburg, Germany, Department of Biology, University of Copenhagen, Archaea Centre, Ole Maaloes Vej 5, DK2200 Copenhagen, Denmark and BIOSS Centre for Biological Signalling Studies, Cluster of Excellence, University of Freiburg, Germany.
authors.forename: Shiraz A
authors.initials: SA
authors.lastname: Shah
authors.affiliation: Department of Computer Science, University of Freiburg, Georges-Köhler-Allee 106, 79110 Freiburg, Germany, Department of Biology, University of Copenhagen, Archaea Centre, Ole Maaloes Vej 5, DK2200 Copenhagen, Denmark and BIOSS Centre for Biological Signalling Studies, Cluster of Excellence, University of Freiburg, Germany.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Garrett
authors.affiliation: Department of Computer Science, University of Freiburg, Georges-Köhler-Allee 106, 79110 Freiburg, Germany, Department of Biology, University of Copenhagen, Archaea Centre, Ole Maaloes Vej 5, DK2200 Copenhagen, Denmark and BIOSS Centre for Biological Signalling Studies, Cluster of Excellence, University of Freiburg, Germany.
authors.forename: Sita J
authors.initials: SJ
authors.lastname: Saunders
authors.affiliation: Department of Computer Science, University of Freiburg, Georges-Köhler-Allee 106, 79110 Freiburg, Germany, Department of Biology, University of Copenhagen, Archaea Centre, Ole Maaloes Vej 5, DK2200 Copenhagen, Denmark and BIOSS Centre for Biological Signalling Studies, Cluster of Excellence, University of Freiburg, Germany Department of Computer Science, University of Freiburg, Georges-Köhler-Allee 106, 79110 Freiburg, Germany, Department of Biology, University of Copenhagen, Archaea Centre, Ole Maaloes Vej 5, DK2200 Copenhagen, Denmark and BIOSS Centre for Biological Signalling Studies, Cluster of Excellence, University of Freiburg, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Backofen
mesh_terms: D001105:Archaea / Q000235:genetics; D001483:Base Sequence; D064113:CRISPR-Cas Systems; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D017124:Conserved Sequence; D056426:Genetic Loci; D058977:Molecular Sequence Annotation; D012313:RNA / Q000096:biosynthesis / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D012984:Software
chemical_list: D012313:RNA