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

Analysis of the singular value decomposition as a tool for processing microarray expression data

We give two informative derivations of a spectral algorithm for clustering and partitioning a bi-partite graph. In the first case we begin with a discrete optimization problem that relaxes into a tractable continuous analogue. In the second case we use the power method to derive an iterative interpretation of the algorithm. Both versions reveal a natural approach for re-scaling the edge weights and help to explain the performance of the algorithm in the presence of outliers. Our motivation for this work is in the analysis of microarray data from bioinformatics, and we give some numerical results for a publicly available acute leukemia data set

Assessing similarity of feature selection techniques in high-dimensional domains

Recent research efforts attempt to combine multiple feature selection techniques instead of using a single one. However, this combination is often made on an “ad hoc” basis, depending on the specific problem at hand, without considering the degree of diversity/similarity of the involved methods. Moreover, though it is recognized that different techniques may return quite dissimilar outputs, especially in high dimensional/small sample size domains, few direct comparisons exist that quantify these differences and their implications on classification performance. This paper aims to provide a contribution in this direction by proposing a general methodology for assessing the similarity between the outputs of different feature selection methods in high dimensional classification problems. Using as benchmark the genomics domain, an empirical study has been conducted to compare some of the most popular feature selection methods, and useful insight has been obtained about their pattern of agreement

Information visualization for DNA microarray data analysis: A critical review

Graphical representation may provide effective means of making sense of the complexity and sheer volume of data produced by DNA microarray experiments that monitor the expression patterns of thousands of genes simultaneously. The ability to use ldquoabstractrdquo graphical representation to draw attention to areas of interest, and more in-depth visualizations to answer focused questions, would enable biologists to move from a large amount of data to particular records they are interested in, and therefore, gain deeper insights in understanding the microarray experiment results. This paper starts by providing some background knowledge of microarray experiments, and then, explains how graphical representation can be applied in general to this problem domain, followed by exploring the role of visualization in gene expression data analysis. Having set the problem scene, the paper then examines various multivariate data visualization techniques that have been applied to microarray data analysis. These techniques are critically reviewed so that the strengths and weaknesses of each technique can be tabulated. Finally, several key problem areas as well as possible solutions to them are discussed as being a source for future work

Predicting Genetic Regulatory Response Using Classification

We present a novel classification-based method for learning to predict gene regulatory response. Our approach is motivated by the hypothesis that in simple organisms such as Saccharomyces cerevisiae, we can learn a decision rule for predicting whether a gene is up- or down-regulated in a particular experiment based on (1) the presence of binding site subsequences (``motifs'') in the gene's regulatory region and (2) the expression levels of regulators such as transcription factors in the experiment (``parents''). Thus our learning task integrates two qualitatively different data sources: genome-wide cDNA microarray data across multiple perturbation and mutant experiments along with motif profile data from regulatory sequences. We convert the regression task of predicting real-valued gene expression measurement to a classification task of predicting +1 and -1 labels, corresponding to up- and down-regulation beyond the levels of biological and measurement noise in microarray measurements. The learning algorithm employed is boosting with a margin-based generalization of decision trees, alternating decision trees. This large-margin classifier is sufficiently flexible to allow complex logical functions, yet sufficiently simple to give insight into the combinatorial mechanisms of gene regulation. We observe encouraging prediction accuracy on experiments based on the Gasch S. cerevisiae dataset, and we show that we can accurately predict up- and down-regulation on held-out experiments. Our method thus provides predictive hypotheses, suggests biological experiments, and provides interpretable insight into the structure of genetic regulatory networks.Comment: 8 pages, 4 figures, presented at Twelfth International Conference on Intelligent Systems for Molecular Biology (ISMB 2004), supplemental website: http://www.cs.columbia.edu/compbio/geneclas

A cDNA Microarray Gene Expression Data Classifier for Clinical Diagnostics Based on Graph Theory

Despite great advances in discovering cancer molecular profiles, the proper application of microarray technology to routine clinical diagnostics is still a challenge. Current practices in the classification of microarrays' data show two main limitations: the reliability of the training data sets used to build the classifiers, and the classifiers' performances, especially when the sample to be classified does not belong to any of the available classes. In this case, state-of-the-art algorithms usually produce a high rate of false positives that, in real diagnostic applications, are unacceptable. To address this problem, this paper presents a new cDNA microarray data classification algorithm based on graph theory and is able to overcome most of the limitations of known classification methodologies. The classifier works by analyzing gene expression data organized in an innovative data structure based on graphs, where vertices correspond to genes and edges to gene expression relationships. To demonstrate the novelty of the proposed approach, the authors present an experimental performance comparison between the proposed classifier and several state-of-the-art classification algorithm

The robust selection of predictive genes via a simple classifier

Identifying genes that direct the mechanism of a disease from expression data is extremely useful in understanding how that mechanism works. This in turn may lead to better diagnoses and potentially can lead to a cure for that disease. This task becomes extremely challenging when the data are characterised by only a small number of samples and a high number of dimensions, as it is often the case with gene expression data. Motivated by this challenge, we present a general framework that focuses on simplicity and data perturbation. These are the keys for the robust identification of the most predictive features in such data. Within this framework, we propose a simple selective na¨ıve Bayes classifier discovered using a global search technique, and combine it with data perturbation to increase its robustness to small sample sizes. An extensive validation of the method was carried out using two applied datasets from the field of microarrays and a simulated dataset, all confounded by small sample sizes and high dimensionality. The method has been shown capable of identifying genes previously confirmed or associated with prostate cancer and viral infections