MOTIVATION: Copy number variations (CNVs) are a major source of genomic variability and are especially significant in cancer. Until recently microarray technologies have been used to characterize CNVs in genomes. However, advances in next-generation sequencing technology offer significant opportunities to deduce copy number directly from genome sequencing data. Unfortunately cancer genomes differ from normal genomes in several aspects that make them far less amenable to copy number detection. For example, cancer genomes are often aneuploid and an admixture of diploid/non-tumor cell fractions. Also patient-derived xenograft models can be laden with mouse contamination that strongly affects accurate assignment of copy number. Hence, there is a need to develop analytical tools that can take into account cancer-specific parameters for detecting CNVs directly from genome sequencing data. RESULTS: We have developed WaveCNV, a software package to identify copy number alterations by detecting breakpoints of CNVs using translation-invariant discrete wavelet transforms and assign digitized copy numbers to each event using next-generation sequencing data. We also assign alleles specifying the chromosomal ratio following duplication/loss. We verified copy number calls using both microarray (correlation coefficient 0.97) and quantitative polymerase chain reaction (correlation coefficient 0.94) and found them to be highly concordant. We demonstrate its utility in pancreatic primary and xenograft sequencing data. AVAILABILITY AND IMPLEMENTATION: Source code and executables are available at https://github.com/WaveCNV. The segmentation algorithm is implemented in MATLAB, and copy number assignment is implemented Perl. CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Case-based reasoning (CBR) is a suitable paradigm for class discovery in molecular biology, where the rules that define the domain knowledge are difficult to obtain and the number and the complexity of the rules affecting the problem are too large for formal knowledge representation. To extend the capabilities of CBR, we propose the mixture of experts for case-based reasoning (MOE4CBR), a method that combines an ensemble of CBR classifiers with spectral clustering and logistic regression. Our approach not only achieves higher prediction accuracy, but also leads to the selection of a subset of features that have meaningful relationships with their class labels. We evaluate MOE4CBR by applying the method to a CBR system called TA3 - a computational framework for CBR systems. For two ovarian mass spectrometry data sets, the prediction accuracy improves from 80 percent to 93 percent and from 90 percent to 98.4 percent, respectively. We also apply the method to leukemia and lung microarray data sets with prediction accuracy improving from 65 percent to 74 percent and from 60 percent to 70 percent, respectively. Finally, we compare our list of discovered biomarkers with the lists of selected biomarkers from other studies for the mass spectrometry data sets.