Summary: The minfi package is widely used for analyzing Illumina DNA methylation array data. Here we describe modifications to the minfi package required to support the HumanMethylationEPIC ('EPIC') array from Illumina. We discuss methods for the joint analysis and normalization of data from the HumanMethylation450 ('450k') and EPIC platforms. We introduce the single-sample Noob ( ssNoob ) method, a normalization procedure suitable for incremental preprocessing of individual methylation arrays and conclude that this method should be used when integrating data from multiple generations of Infinium methylation arrays. We show how to use reference 450k datasets to estimate cell type composition of samples on EPIC arrays. The cumulative effect of these updates is to ensure that minfi provides the tools to best integrate existing and forthcoming Illumina methylation array data. Availability and Implementation: The minfi package version 1.19.12 or higher is available for all platforms from the Bioconductor project. Contact: [email protected]. Supplementary information: Supplementary data are available at Bioinformatics online.

MOTIVATION: Three major problems confront the construction of a human genetic network from heterogeneous genomics data using kernel-based approaches: definition of a robust gold-standard negative set, large-scale learning and massive missing data values. RESULTS: The proposed graph-based approach generates a robust GSN for the training process of genetic network construction. The RVM-based ensemble model that combines AdaBoost and reduced-feature yields improved performance on large-scale learning problems with massive missing values in comparison to Naïve Bayes. CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary material is available at Bioinformatics online.

MOTIVATION: Genomic instability in cancer leads to abnormal genome copy number alterations (CNA) that are associated with the development and behavior of tumors. Advances in microarray technology have allowed for greater resolution in detection of DNA copy number changes (amplifications or deletions) across the genome. However, the increase in number of measured signals and accompanying noise from the array probes present a challenge in accurate and fast identification of breakpoints that define CNA. This article proposes a novel detection technique that exploits the use of piece wise constant (PWC) vectors to represent genome copy number and sparse Bayesian learning (SBL) to detect CNA breakpoints. METHODS: First, a compact linear algebra representation for the genome copy number is developed from normalized probe intensities. Second, SBL is applied and optimized to infer locations where copy number changes occur. Third, a backward elimination (BE) procedure is used to rank the inferred breakpoints; and a cut-off point can be efficiently adjusted in this procedure to control for the false discovery rate (FDR). RESULTS: The performance of our algorithm is evaluated using simulated and real genome datasets and compared to other existing techniques. Our approach achieves the highest accuracy and lowest FDR while improving computational speed by several orders of magnitude. The proposed algorithm has been developed into a free standing software application (GADA, Genome Alteration Detection Algorithm). AVAILABILITY: http://biron.usc.edu/~piquereg/GADA

MOTIVATION: A number of algorithms have been proposed for the processing of feature-level data from high-density oligonucleotide microarrays to give estimates of transcript abundance. Performance in the common task of detecting differential expression between samples can be quantified by the statistical concepts of sensitivity and specificity, and represented by the use of receiver operating characteristic curves. These have been previously presented for small numbers of genes known to be differentially present in spiked-in samples. We present here a study of performance over a large number (thousands) of transcripts for which there is strong evidence of differential expression, with corresponding false positive rates controlled by comparisons between replicates. RESULTS: The straight-line regression analysis of a mixture series with replicates by five estimation algorithms produces a consensus set of 4462 transcripts with differential expression of agreed direction and high significance (p < 0.01) according to all algorithms. The more difficult task of two-sample tests between adjacent mixture levels produces performance curves of fraction true positive detected against significance level. Performance varies significantly between algorithms: at the p < 0.01 level, the detection rate varies between 41 and 66%. A control using comparisons between replicates at the same levels indicates that the tests produce empirical false positive rates closely matching the nominal p-values.