title: A scale-space method for detecting recurrent DNA copy number changes with analytical false discovery rate control.
abstract: Tumor formation is partially driven by DNA copy number changes, which are typically measured using array comparative genomic hybridization, SNP arrays and DNA sequencing platforms. Many techniques are available for detecting recurring aberrations across multiple tumor samples, including CMAR, STAC, GISTIC and KC-SMART. GISTIC is widely used and detects both broad and focal (potentially overlapping) recurring events. However, GISTIC performs false discovery rate control on probes instead of events. Here we propose Analytical Multi-scale Identification of Recurrent Events, a multi-scale Gaussian smoothing approach, for the detection of both broad and focal (potentially overlapping) recurring copy number alterations. Importantly, false discovery rate control is performed analytically (no need for permutations) on events rather than probes. The method does not require segmentation or calling on the input dataset and therefore reduces the potential loss of information due to discretization. An important characteristic of the approach is that the error rate is controlled across all scales and that the algorithm outputs a single profile of significant events selected from the appropriate scales. We perform extensive simulations and showcase its utility on a glioblastoma SNP array dataset. Importantly, ADMIRE detects focal events that are missed by GISTIC, including two events involving known glioma tumor-suppressor genes: CDKN2C and NF1.
authors.affiliation: Bioinformatics and Statistics group, Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Ewald
authors.initials: E
authors.lastname: van Dyk
authors.forename: Marcel J T
authors.initials: MJ
authors.lastname: Reinders
authors.forename: Lodewyk F A
authors.initials: LF
authors.lastname: Wessels
mesh_terms: D000465:Algorithms; D056915:DNA Copy Number Variations; D004273:DNA, Neoplasm / Q000032:analysis*; D003627:Data Interpretation, Statistical; D023281:Genomics / Q000379:methods; D005910:Glioma / Q000235:genetics; D006801:Humans
chemical_list: D004273:DNA, Neoplasm