title: A fused lasso latent feature model for analyzing multi-sample aCGH data.
abstract: Array-based comparative genomic hybridization (aCGH) enables the measurement of DNA copy number across thousands of locations in a genome. The main goals of analyzing aCGH data are to identify the regions of copy number variation (CNV) and to quantify the amount of CNV. Although there are many methods for analyzing single-sample aCGH data, the analysis of multi-sample aCGH data is a relatively new area of research. Further, many of the current approaches for analyzing multi-sample aCGH data do not appropriately utilize the additional information present in the multiple samples. We propose a procedure called the Fused Lasso Latent Feature Model (FLLat) that provides a statistical framework for modeling multi-sample aCGH data and identifying regions of CNV. The procedure involves modeling each sample of aCGH data as a weighted sum of a fixed number of features. Regions of CNV are then identified through an application of the fused lasso penalty to each feature. Some simulation analyses show that FLLat outperforms single-sample methods when the simulated samples share common information. We also propose a method for estimating the false discovery rate. An analysis of an aCGH data set obtained from human breast tumors, focusing on chromosomes 8 and 17, shows that FLLat and Significance Testing of Aberrant Copy number (an alternative, existing approach) identify similar regions of CNV that are consistent with previous findings. However, through the estimated features and their corresponding weights, FLLat is further able to discern specific relationships between the samples, for example, identifying 3 distinct groups of samples based on their patterns of CNV for chromosome 17.
authors.affiliation: Department of Biostatistics, Harvard University, Boston, MA 02115, USA. gen.nowak@gmail.com
authors.forename: Gen
authors.initials: G
authors.lastname: Nowak
authors.forename: Trevor
authors.initials: T
authors.lastname: Hastie
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Pollack
authors.forename: Robert
authors.initials: R
authors.lastname: Tibshirani
mesh_terms: D056808:Biostatistics; D001943:Breast Neoplasms / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D055028:Comparative Genomic Hybridization / Q000706:statistics & numerical data*; D056915:DNA Copy Number Variations; D003627:Data Interpretation, Statistical; D005260:Female; D006801:Humans; D015233:Models, Statistical