Stability and aggregation of ranked gene lists

Ranked gene lists are highly instable in the sense that similar measures of differential gene expression may yield very different rankings, and that a small change of the data set usually affects the obtained gene list considerably. Stability issues have long been under-considered in the literature, but they have grown to a hot topic in the last few years, perhaps as a consequence of the increasing skepticism on the reproducibility and clinical applicability of molecular research findings. In this article, we review existing approaches for the assessment of stability of ranked gene lists and the related problem of aggregation, give some practical recommendations, and warn against potential misuse of these methods. This overview is illustrated through an application to a recent leukemia data set using the freely available Bioconductor package GeneSelector

Techniques for clustering gene expression data

Many clustering techniques have been proposed for the analysis of gene expression data obtained from microarray experiments. However, choice of suitable method(s) for a given experimental dataset is not straightforward. Common approaches do not translate well and fail to take account of the data profile. This review paper surveys state of the art applications which recognises these limitations and implements procedures to overcome them. It provides a framework for the evaluation of clustering in gene expression analyses. The nature of microarray data is discussed briefly. Selected examples are presented for the clustering methods considered

Learning Heterogeneous Similarity Measures for Hybrid-Recommendations in Meta-Mining

The notion of meta-mining has appeared recently and extends the traditional meta-learning in two ways. First it does not learn meta-models that provide support only for the learning algorithm selection task but ones that support the whole data-mining process. In addition it abandons the so called black-box approach to algorithm description followed in meta-learning. Now in addition to the datasets, algorithms also have descriptors, workflows as well. For the latter two these descriptions are semantic, describing properties of the algorithms. With the availability of descriptors both for datasets and data mining workflows the traditional modelling techniques followed in meta-learning, typically based on classification and regression algorithms, are no longer appropriate. Instead we are faced with a problem the nature of which is much more similar to the problems that appear in recommendation systems. The most important meta-mining requirements are that suggestions should use only datasets and workflows descriptors and the cold-start problem, e.g. providing workflow suggestions for new datasets. In this paper we take a different view on the meta-mining modelling problem and treat it as a recommender problem. In order to account for the meta-mining specificities we derive a novel metric-based-learning recommender approach. Our method learns two homogeneous metrics, one in the dataset and one in the workflow space, and a heterogeneous one in the dataset-workflow space. All learned metrics reflect similarities established from the dataset-workflow preference matrix. We demonstrate our method on meta-mining over biological (microarray datasets) problems. The application of our method is not limited to the meta-mining problem, its formulations is general enough so that it can be applied on problems with similar requirements

Bioinformatics tools in predictive ecology: Applications to fisheries

This article is made available throught the Brunel Open Access Publishing Fund - Copygith @ 2012 Tucker et al.There has been a huge effort in the advancement of analytical techniques for molecular biological data over the past decade. This has led to many novel algorithms that are specialized to deal with data associated with biological phenomena, such as gene expression and protein interactions. In contrast, ecological data analysis has remained focused to some degree on off-the-shelf statistical techniques though this is starting to change with the adoption of state-of-the-art methods, where few assumptions can be made about the data and a more explorative approach is required, for example, through the use of Bayesian networks. In this paper, some novel bioinformatics tools for microarray data are discussed along with their ‘crossover potential’ with an application to fisheries data. In particular, a focus is made on the development of models that identify functionally equivalent species in different fish communities with the aim of predicting functional collapse

Feature selection for microarray gene expression data using simulated annealing guided by the multivariate joint entropy

In this work a new way to calculate the multivariate joint entropy is presented. This measure is the basis for a fast information-theoretic based evaluation of gene relevance in a Microarray Gene Expression data context. Its low complexity is based on the reuse of previous computations to calculate current feature relevance. The mu-TAFS algorithm --named as such to differentiate it from previous TAFS algorithms-- implements a simulated annealing technique specially designed for feature subset selection. The algorithm is applied to the maximization of gene subset relevance in several public-domain microarray data sets. The experimental results show a notoriously high classification performance and low size subsets formed by biologically meaningful genes.Postprint (published version

Application of Volcano Plots in Analyses of mRNA Differential Expressions with Microarrays

Volcano plot displays unstandardized signal (e.g. log-fold-change) against noise-adjusted/standardized signal (e.g. t-statistic or -log10(p-value) from the t test). We review the basic and an interactive use of the volcano plot, and its crucial role in understanding the regularized t-statistic. The joint filtering gene selection criterion based on regularized statistics has a curved discriminant line in the volcano plot, as compared to the two perpendicular lines for the "double filtering" criterion. This review attempts to provide an unifying framework for discussions on alternative measures of differential expression, improved methods for estimating variance, and visual display of a microarray analysis result. We also discuss the possibility to apply volcano plots to other fields beyond microarray.Comment: 8 figure

Feature Selection via Binary Simultaneous Perturbation Stochastic Approximation

Feature selection (FS) has become an indispensable task in dealing with today's highly complex pattern recognition problems with massive number of features. In this study, we propose a new wrapper approach for FS based on binary simultaneous perturbation stochastic approximation (BSPSA). This pseudo-gradient descent stochastic algorithm starts with an initial feature vector and moves toward the optimal feature vector via successive iterations. In each iteration, the current feature vector's individual components are perturbed simultaneously by random offsets from a qualified probability distribution. We present computational experiments on datasets with numbers of features ranging from a few dozens to thousands using three widely-used classifiers as wrappers: nearest neighbor, decision tree, and linear support vector machine. We compare our methodology against the full set of features as well as a binary genetic algorithm and sequential FS methods using cross-validated classification error rate and AUC as the performance criteria. Our results indicate that features selected by BSPSA compare favorably to alternative methods in general and BSPSA can yield superior feature sets for datasets with tens of thousands of features by examining an extremely small fraction of the solution space. We are not aware of any other wrapper FS methods that are computationally feasible with good convergence properties for such large datasets.Comment: This is the Istanbul Sehir University Technical Report #SHR-ISE-2016.01. A short version of this report has been accepted for publication at Pattern Recognition Letter

Gene Expression based Survival Prediction for Cancer Patients: A Topic Modeling Approach

Cancer is one of the leading cause of death, worldwide. Many believe that genomic data will enable us to better predict the survival time of these patients, which will lead to better, more personalized treatment options and patient care. As standard survival prediction models have a hard time coping with the high-dimensionality of such gene expression (GE) data, many projects use some dimensionality reduction techniques to overcome this hurdle. We introduce a novel methodology, inspired by topic modeling from the natural language domain, to derive expressive features from the high-dimensional GE data. There, a document is represented as a mixture over a relatively small number of topics, where each topic corresponds to a distribution over the words; here, to accommodate the heterogeneity of a patient's cancer, we represent each patient (~document) as a mixture over cancer-topics, where each cancer-topic is a mixture over GE values (~words). This required some extensions to the standard LDA model eg: to accommodate the "real-valued" expression values - leading to our novel "discretized" Latent Dirichlet Allocation (dLDA) procedure. We initially focus on the METABRIC dataset, which describes breast cancer patients using the r=49,576 GE values, from microarrays. Our results show that our approach provides survival estimates that are more accurate than standard models, in terms of the standard Concordance measure. We then validate this approach by running it on the Pan-kidney (KIPAN) dataset, over r=15,529 GE values - here using the mRNAseq modality - and find that it again achieves excellent results. In both cases, we also show that the resulting model is calibrated, using the recent "D-calibrated" measure. These successes, in two different cancer types and expression modalities, demonstrates the generality, and the effectiveness, of this approach