title: Penalized weighted low-rank approximation for robust recovery of recurrent copy number variations.
abstract: BACKGROUND
  Copy number variation (CNV) analysis has become one of the most important research areas for understanding complex disease. With increasing resolution of array-based comparative genomic hybridization (aCGH) arrays, more and more raw copy number data are collected for multiple arrays. It is natural to realize the co-existence of both recurrent and individual-specific CNVs, together with the possible data contamination during the data generation process. Therefore, there is a great need for an efficient and robust statistical model for simultaneous recovery of both recurrent and individual-specific CNVs.
  
  
  RESULTS
  We develop a penalized weighted low-rank approximation method (WPLA) for robust recovery of recurrent CNVs. In particular, we formulate multiple aCGH arrays into a realization of a hidden low-rank matrix with some random noises and let an additional weight matrix account for those individual-specific effects. Thus, we do not restrict the random noise to be normally distributed, or even homogeneous. We show its performance through three real datasets and twelve synthetic datasets from different types of recurrent CNV regions associated with either normal random errors or heavily contaminated errors.
  
  
  CONCLUSIONS
  Our numerical experiments have demonstrated that the WPLA can successfully recover the recurrent CNV patterns from raw data under different scenarios. Compared with two other recent methods, it performs the best regarding its ability to simultaneously detect both recurrent and individual-specific CNVs under normal random errors. More importantly, the WPLA is the only method which can effectively recover the recurrent CNVs region when the data is heavily contaminated.
authors.affiliation: Department of Mathematics and Statistics, University of North Carolina at Greensboro, 1400 Spring Garden St, Greensoboro, NC, USA. x_gao2@uncg.edu.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Gao
mesh_terms: D000465:Algorithms; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D055028:Comparative Genomic Hybridization / Q000379:methods*; D019295:Computational Biology / Q000379:methods*; D056915:DNA Copy Number Variations / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D015233:Models, Statistical