DNA copy number change is an important form of structural variations in human genomes. Detecting copy number changes using DNA array data is a challenging task due to high density genomic loci, low signal to noise ratios, and normal tissue contamination. We propose fused margin regression (FMR) method that combines a variable fusion rule and robust epsilon-insensitive loss criterion to approximate piecewise constant segments of the underlying copy number profile. We tested FMR on both simulation and real CGH and SNP array datasets, and observed competitively improved performance as compared to several widely-adopted existing methods.

Though supervised and unsupervised analyses of genomic data have been intensively studied in recent years, little effort has been made to discover the structural information contained in the data. In this work, we propose a stability analysis guided supervised clustering and visualization method aiming to discover the hierarchical structure in gene expression data, which we call the "tree of phenotypes". We applied the method on two multiclass gene expression microarray data sets and presented the biological plausibility of the learned trees. We also tested the multiclass classifiers built on the learned trees and demonstrated their good classification performance

MOTIVATION: Multilayer perceptrons (MLP) represent one of the widely used and effective machine learning methods currently applied to diagnostic classification based on high-dimensional genomic data. Since the dimensionalities of the existing genomic data often exceed the available sample sizes by orders of magnitude, the MLP performance may degrade owing to the curse of dimensionality and over-fitting, and may not provide acceptable prediction accuracy. RESULTS: Based on Fisher linear discriminant analysis, we designed and implemented an MLP optimization scheme for a two-layer MLP that effectively optimizes the initialization of MLP parameters and MLP architecture. The optimized MLP consistently demonstrated its ability in easing the curse of dimensionality in large microarray datasets. In comparison with a conventional MLP using random initialization, we obtained significant improvements in major performance measures including Bayes classification accuracy, convergence properties and area under the receiver operating characteristic curve (A(z)). SUPPLEMENTARY INFORMATION: The Supplementary information is available on http://www.cbil.ece.vt.edu/publications.htm