A mixture model with a reference-based automatic selection of components for disease classification from protein and/or gene expression levels

Background Bioinformatics data analysis is often using linear mixture model representing samples as additive mixture of components. Properly constrained blind matrix factorization methods extract those components using mixture samples only. However, automatic selection of extracted components to be retained for classification analysis remains an open issue. Results The method proposed here is applied to well-studied protein and genomic datasets of ovarian, prostate and colon cancers to extract components for disease prediction. It achieves average sensitivities of: 96.2 (sd=2.7%), 97.6% (sd=2.8%) and 90.8% (sd=5.5%) and average specificities of: 93.6% (sd=4.1%), 99% (sd=2.2%) and 79.4% (sd=9.8%) in 100 independent two-fold cross-validations. Conclusions We propose an additive mixture model of a sample for feature extraction using, in principle, sparseness constrained factorization on a sample-by-sample basis. As opposed to that, existing methods factorize complete dataset simultaneously. The sample model is composed of a reference sample representing control and/or case (disease) groups and a test sample. Each sample is decomposed into two or more components that are selected automatically (without using label information) as control specific, case specific and not differentially expressed (neutral). The number of components is determined by cross-validation. Automatic assignment of features (m/z ratios or genes) to particular component is based on thresholds estimated from each sample directly. Due to the locality of decomposition, the strength of the expression of each feature across the samples can vary. Yet, they will still be allocated to the related disease and/or control specific component. Since label information is not used in the selection process, case and control specific components can be used for classification. That is not the case with standard factorization methods. Moreover, the component selected by proposed method as disease specific can be interpreted as a sub-mode and retained for further analysis to identify potential biomarkers. As opposed to standard matrix factorization methods this can be achieved on a sample (experiment)-by-sample basis. Postulating one or more components with indifferent features enables their removal from disease and control specific components on a sample-by-sample basis. This yields selected components with reduced complexity and generally, it increases prediction accuracy

Hybridizing sparse component analysis with genetic algorithms for microarray analysis

Nonnegative matrix factorization (NMF) has proven to be a useful tool for the previous termanalysisnext term of nonnegative multivariate data. However, it is known not to lead to unique results when applied to blind source separation (BSS) problems. In this paper we present an extension of NMF capable of solving the BSS problem when the underlying sources are sufficiently previous termsparse.next term In contrast to most well-established BSS methods, the devised previous termalgorithmnext term is capable of solving the BSS problem in cases where the underlying sources are not independent or uncorrelated. As the proposed fitness function is discontinuous and possesses many local minima, we use a previous termgenetic algorithmnext term for its minimization. Finally, we apply the devised previous termalgorithmnext term to real world previous termmicroarraynext term data