Stable Feature Selection for Biomarker Discovery

Feature selection techniques have been used as the workhorse in biomarker discovery applications for a long time. Surprisingly, the stability of feature selection with respect to sampling variations has long been under-considered. It is only until recently that this issue has received more and more attention. In this article, we review existing stable feature selection methods for biomarker discovery using a generic hierarchal framework. We have two objectives: (1) providing an overview on this new yet fast growing topic for a convenient reference; (2) categorizing existing methods under an expandable framework for future research and development

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.Siemens AG, MunichDFG (Graduate College 638)DAAD (PPP Luso - Alem˜a and PPP Hispano - Alemanas

Developing a discrimination rule between breast cancer patients and controls using proteomics mass spectrometric data: A three-step approach

To discriminate between breast cancer patients and controls, we used a three-step approach to obtain our decision rule. First, we ranked the mass/charge values using random forests, because it generates importance indices that take possible interactions into account. We observed that the top ranked variables consisted of highly correlated contiguous mass/charge values, which were grouped in the second step into new variables. Finally, these newly created variables were used as predictors to find a suitable discrimination rule. In this last step, we compared three different methods, namely Classification and Regression Tree ( CART), logistic regression and penalized logistic regression. Logistic regression and penalized logistic regression performed equally well and both had a higher classification accuracy than CART. The model obtained with penalized logistic regression was chosen as we hypothesized that this model would provide a better classification accuracy in the validation set. The solution had a good performance on the training set with a classification accuracy of 86.3%, and a sensitivity and specificity of 86.8% and 85.7%, respectively

Isoform-level gene signature improves prognostic stratification and accurately classifies glioblastoma subtypes.

Molecular stratification of tumors is essential for developing personalized therapies. Although patient stratification strategies have been successful; computational methods to accurately translate the gene-signature from high-throughput platform to a clinically adaptable low-dimensional platform are currently lacking. Here, we describe PIGExClass (platform-independent isoform-level gene-expression based classification-system), a novel computational approach to derive and then transfer gene-signatures from one analytical platform to another. We applied PIGExClass to design a reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) based molecular-subtyping assay for glioblastoma multiforme (GBM), the most aggressive primary brain tumors. Unsupervised clustering of TCGA (the Cancer Genome Altas Consortium) GBM samples, based on isoform-level gene-expression profiles, recaptured the four known molecular subgroups but switched the subtype for 19% of the samples, resulting in significant (P = 0.0103) survival differences among the refined subgroups. PIGExClass derived four-class classifier, which requires only 121 transcript-variants, assigns GBM patients' molecular subtype with 92% accuracy. This classifier was translated to an RT-qPCR assay and validated in an independent cohort of 206 GBM samples. Our results demonstrate the efficacy of PIGExClass in the design of clinically adaptable molecular subtyping assay and have implications for developing robust diagnostic assays for cancer patient stratification

Gene set based ensemble methods for cancer classification

Diagnosis of cancer very often depends on conclusions drawn after both clinical and microscopic examinations of tissues to study the manifestation of the disease in order to place tumors in known categories. One factor which determines the categorization of cancer is the tissue from which the tumor originates. Information gathered from clinical exams may be partial or not completely predictive of a specific category of cancer. Further complicating the problem of categorizing various tumors is that the histological classification of the cancer tissue and description of its course of development may be atypical. Gene expression data gleaned from micro-array analysis provides tremendous promise for more accurate cancer diagnosis. One hurdle in the classification of tumors based on gene expression data is that the data space is ultra-dimensional with relatively few points; that is, there are a small number of examples with a large number of genes. A second hurdle is expression bias caused by the correlation of genes. Analysis of subsets of genes, known as gene set analysis, provides a mechanism by which groups of differentially expressed genes can be identified. We propose an ensemble of classifiers whose base classifiers are ℓ1-regularized logistic regression models with restriction of the feature space to biologically relevant genes. Some researchers have already explored the use of ensemble classifiers to classify cancer but the effect of the underlying base classifiers in conjunction with biologically-derived gene sets on cancer classification has not been explored

Boosting Correlation Based Penalization in Generalized Linear Models

In high dimensional regression problems penalization techniques are a useful tool for estimation and variable selection. We propose a novel penalization technique that aims at the grouping effect which encourages strongly correlated predictors to be in or out of the model together. The proposed penalty uses the correlation between predictors explicitly. We consider a simple version that does not select variables and a boosted version which is able to reduce the number of variables in the model. Both methods are derived within the framework of generalized linear models. The performance is evaluated by simulations and by use of real world data sets

Ensemble transcript interaction networks: A case study on Alzheimer's disease

Systems biology techniques are a topic of recent interest within the neurological field. Computational intelligence (CI) addresses this holistic perspective by means of consensus or ensemble techniques ultimately capable of uncovering new and relevant findings. In this paper, we propose the application of a CI approach based on ensemble Bayesian network classifiers and multivariate feature subset selection to induce probabilistic dependences that could match or unveil biological relationships. The research focuses on the analysis of high-throughput Alzheimer's disease (AD) transcript profiling. The analysis is conducted from two perspectives. First, we compare the expression profiles of hippocampus subregion entorhinal cortex (EC) samples of AD patients and controls. Second, we use the ensemble approach to study four types of samples: EC and dentate gyrus (DG) samples from both patients and controls. Results disclose transcript interaction networks with remarkable structures and genes not directly related to AD by previous studies. The ensemble is able to identify a variety of transcripts that play key roles in other neurological pathologies. Classical statistical assessment by means of non-parametric tests confirms the relevance of the majority of the transcripts. The ensemble approach pinpoints key metabolic mechanisms that could lead to new findings in the pathogenesis and development of A

Knowledge management overview of feature selection problem in high-dimensional financial data: Cooperative co-evolution and Map Reduce perspectives

The term big data characterizes the massive amounts of data generation by the advanced technologies in different domains using 4Vs volume, velocity, variety, and veracity-to indicate the amount of data that can only be processed via computationally intensive analysis, the speed of their creation, the different types of data, and their accuracy. High-dimensional financial data, such as time-series and space-Time data, contain a large number of features (variables) while having a small number of samples, which are used to measure various real-Time business situations for financial organizations. Such datasets are normally noisy, and complex correlations may exist between their features, and many domains, including financial, lack the al analytic tools to mine the data for knowledge discovery because of the high-dimensionality. Feature selection is an optimization problem to find a minimal subset of relevant features that maximizes the classification accuracy and reduces the computations. Traditional statistical-based feature selection approaches are not adequate to deal with the curse of dimensionality associated with big data. Cooperative co-evolution, a meta-heuristic algorithm and a divide-And-conquer approach, decomposes high-dimensional problems into smaller sub-problems. Further, MapReduce, a programming model, offers a ready-To-use distributed, scalable, and fault-Tolerant infrastructure for parallelizing the developed algorithm. This article presents a knowledge management overview of evolutionary feature selection approaches, state-of-The-Art cooperative co-evolution and MapReduce-based feature selection techniques, and future research directions