Knowledge-based gene expression classification via matrix factorization.

MOTIVATION: Modern machine learning methods based on matrix decomposition techniques, like independent component analysis (ICA) or non-negative matrix factorization (NMF), provide new and efficient analysis tools which are currently explored to analyze gene expression profiles. These exploratory feature extraction techniques yield expression modes (ICA) or metagenes (NMF). These extracted features are considered indicative of underlying regulatory processes. They can as well be applied to the classification of gene expression datasets by grouping samples into different categories for diagnostic purposes or group genes into functional categories for further investigation of related metabolic pathways and regulatory networks. RESULTS: In this study we focus on unsupervised matrix factorization techniques and apply ICA and sparse NMF to microarray datasets. The latter monitor the gene expression levels of human peripheral blood cells during differentiation from monocytes to macrophages. We show that these tools are able to identify relevant signatures in the deduced component matrices and extract informative sets of marker genes from these gene expression profiles. The methods rely on the joint discriminative power of a set of marker genes rather than on single marker genes. With these sets of marker genes, corroborated by leave-one-out or random forest cross-validation, the datasets could easily be classified into related diagnostic categories. The latter correspond to either monocytes versus macrophages or healthy vs Niemann Pick C disease patients.

Comparison of unsupervised and supervised gene selection methods.

Modern machine learning methods based on matrix decomposition techniques like Independent Component Analysis (ICA) provide new and efficient analysis tools which are currently explored to analyze gene expression profiles. These exploratory feature extraction techniques yield informative expression modes (ICA) which are considered indicative of underlying regulatory processes. Their most strongly expressed genes represent marker genes for classification of the tissue samples under investigation. Comparison with supervised gene selection methods based on statistical scores or support vector machines corroborate these findings. The method is applied to macrophages loaded/de-loaded with chemically modified low density lipids.

How to extract marker genes from microarray data sets.

In this study we focus on classification tasks and apply matrix factorization techniques like principal component analysis (PCA), independent component analysis (ICA) and non-negative matrix factorization (NMF) to a microarray data set. The latter monitors the gene expression levels (GEL) of mononcytes and macrophages during and after differentiation. We show that these tools are able to identify relevant signatures in the deduced matrices and extract marker genes from these gene expression profiles (GEPs) without the need for extensive data bank search for appropriate functional annotations. With these marker genes corresponding test data sets can then easily be classified into related diagnostic categories.

Routes to identify marker genes for microarray classification.

Support vector machines are applied to extract marker genes from various microarray data sets: Breast Cancer, Leukemia and Monocyte - Macrophage Differentiation to ease classification of related pathologies or characterize related gene regulation pathways.