title: GOTHiC, a probabilistic model to resolve complex biases and to identify real interactions in Hi-C data.
abstract: Hi-C is one of the main methods for investigating spatial co-localisation of DNA in the nucleus. However, the raw sequencing data obtained from Hi-C experiments suffer from large biases and spurious contacts, making it difficult to identify true interactions. Existing methods use complex models to account for biases and do not provide a significance threshold for detecting interactions. Here we introduce a simple binomial probabilistic model that resolves complex biases and distinguishes between true and false interactions. The model corrects biases of known and unknown origin and yields a p-value for each interaction, providing a reliable threshold based on significance. We demonstrate this experimentally by testing the method against a random ligation dataset. Our method outperforms previous methods and provides a statistical framework for further data analysis, such as comparisons of Hi-C interactions between different conditions. GOTHiC is available as a BioConductor package (http://www.bioconductor.org/packages/release/bioc/html/GOTHiC.html).
authors.affiliation: The Francis Crick Institute, London, United Kingdom.|UCL Genetics Institute, Department of Genetics Evolution and Environment, University College London, London, United Kingdom.
authors.forename: Borbala
authors.identifier: http://orcid.org/0000-0003-3429-3094
authors.initials: B
authors.lastname: Mifsud
authors.affiliation: The Francis Crick Institute, London, United Kingdom.
authors.forename: Inigo
authors.initials: I
authors.lastname: Martincorena
authors.affiliation: The Francis Crick Institute, London, United Kingdom.
authors.forename: Elodie
authors.initials: E
authors.lastname: Darbo
authors.affiliation: The Francis Crick Institute, London, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Sugar
authors.affiliation: Nuclear Dynamics Programme, Babraham Institute, Cambridge, United Kingdom.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schoenfelder
authors.affiliation: Nuclear Dynamics Programme, Babraham Institute, Cambridge, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Fraser
authors.affiliation: The Francis Crick Institute, London, United Kingdom.|UCL Genetics Institute, Department of Genetics Evolution and Environment, University College London, London, United Kingdom.|Okinawa Institute of Science & Technology, Okinawa, Japan.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Luscombe
mesh_terms: D015982:Bias; D002875:Chromosomes / Q000235:genetics* / Q000648:ultrastructure; D019295:Computational Biology / Q000379:methods*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D056426:Genetic Loci / Q000235:genetics*; D015233:Models, Statistical; D012984:Software
chemical_list: D004247:DNA