title: Mixture models and wavelet transforms reveal high confidence RNA-protein interaction sites in MOV10 PAR-CLIP data.
abstract: The Photo-Activatable Ribonucleoside-enhanced CrossLinking and ImmunoPrecipitation (PAR-CLIP) method was recently developed for global identification of RNAs interacting with proteins. The strength of this versatile method results from induction of specific T to C transitions at sites of interaction. However, current analytical tools do not distinguish between non-experimentally and experimentally induced transitions. Furthermore, geometric properties at potential binding sites are not taken into account. To surmount these shortcomings, we developed a two-step algorithm consisting of a non-parametric two-component mixture model and a wavelet-based peak calling procedure. Our algorithm can reduce the number of false positives up to 24% thereby identifying high confidence interaction sites. We successfully employed this approach in conjunction with a modified PAR-CLIP protocol to study the functional role of nuclear Moloney leukemia virus 10, a putative RNA helicase interacting with Argonaute2 and Polycomb. Our method, available as the R package wavClusteR, is generally applicable to any substitution-based inference problem in genomics.
authors: Department of Biosystems Science and Engineering, Swiss Federal Institute of Technology Zurich, Mattenstrasse 26, 4058 Basel, Switzerland.
authors: Cem
authors: C
authors: Sievers
authors: Tommy
authors: T
authors: Schlumpf
authors: Ritwick
authors: R
authors: Sawarkar
authors: Federico
authors: F
authors: Comoglio
authors: Renato
authors: R
authors: Paro
mesh_terms: D000465:Algorithms; D001499:Bayes Theorem; D001665:Binding Sites; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D015233:Models, Statistical; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D020365:RNA Helicases / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D058067:Wavelet Analysis
chemical_list: D016601:RNA-Binding Proteins; D012313:RNA; C530476:Mov10 protein, human; D020365:RNA Helicases