Classification and biomarker identification using gene network modules and support vector machines

<p>Abstract</p> <p>Background</p> <p>Classification using microarray datasets is usually based on a small number of samples for which tens of thousands of gene expression measurements have been obtained. The selection of the genes most significant to the classification problem is a challenging issue in high dimension data analysis and interpretation. A previous study with SVM-RCE (Recursive Cluster Elimination), suggested that classification based on groups of correlated genes sometimes exhibits better performance than classification using single genes. Large databases of gene interaction networks provide an important resource for the analysis of genetic phenomena and for classification studies using interacting genes.</p> <p>We now demonstrate that an algorithm which integrates network information with recursive feature elimination based on SVM exhibits good performance and improves the biological interpretability of the results. We refer to the method as SVM with Recursive Network Elimination (SVM-RNE)</p> <p>Results</p> <p>Initially, one thousand genes selected by t-test from a training set are filtered so that only genes that map to a gene network database remain. The Gene Expression Network Analysis Tool (GXNA) is applied to the remaining genes to form <it>n </it>clusters of genes that are highly connected in the network. Linear SVM is used to classify the samples using these clusters, and a weight is assigned to each cluster based on its importance to the classification. The least informative clusters are removed while retaining the remainder for the next classification step. This process is repeated until an optimal classification is obtained.</p> <p>Conclusion</p> <p>More than 90% accuracy can be obtained in classification of selected microarray datasets by integrating the interaction network information with the gene expression information from the microarrays.</p> <p>The Matlab version of SVM-RNE can be downloaded from <url>http://web.macam.ac.il/~myousef</url></p

One-class Machine Learning Approach for fMRI Analysis

One-Class Machine Learning techniques (i.e. "bottleneck" neural networks and one-class support vector machines (SVM)) are applied to classify whether a subject is performing a task or not by looking solely at the raw fMRI slices of his brain. "One-class" means that during training the system only has access to positive (i.e. task performing) examples. "Two-class" means it has access to negative examples as well. Successful classification of data by a system trained under either of the one-class systems was accomplished at close to the 60% level. (In contrast, an implementation of a standard two class SVM succeeds at around the 70% level.) These results were stable over repeated experiments and for both motor and visual tasks. Since the one-class neural network technique is naturally related to dimension reduction, it is possible that this mechanism may also be used for feature selection

Non-parametric temporal modeling of the hemodynamic response function via a liquid state machine

Standard methods for the analysis of functional MRI data strongly rely on prior implicit and explicit hypotheses made to simplify the analysis. In this work the attention is focused on two such commonly accepted hypotheses: (i) the hemodynamic response function (HRF) to be searched in the BOLD signal can be described by a specific parametric model e.g., double-gamma; (ii) the effect of stimuli on the signal is taken to be linearly additive. While these assumptions have been empirically proven to generate high sensitivity for statistical methods, they also limit the identification of relevant voxels to what is already postulated in the signal, thus not allowing the discovery of unknown correlates in the data due to the presence of unexpected hemodynamics. This paper tries to overcome these limitations by proposing a method wherein the HRF is learned directly from data rather than induced from its basic form assumed in advance. This approach produces a set of voxel-wise models of HRF and, as a result, relevant voxels are filterable according to the accuracy of their prediction in a machine learning framework. This approach is instantiated using a temporal architecture based on the paradigm of Reservoir Computing wherein a Liquid State Machine is combined with a decoding Feed-Forward Neural Network. This splits the modeling into two parts: first a representation of the complex temporal reactivity of the hemodynamic response is determined by a universal global "reservoir" which is essentially temporal; second an interpretation of the encoded representation is determined by a standard feed-forward neural network, which is trained by the data. Thus the reservoir models the temporal state of information during and following temporal stimuli in a feed-back system, while the neural network "translates" this data to fit the specific HRF response as given, e.g. by BOLD signal measurements in fMRI. An empirical analysis on synthetic datasets shows that the learning process can be robust both to noise and to the varying shape of the underlying HRF. A similar investigation on real fMRI datasets provides evidence that BOLD predictability allows for discrimination between relevant and irrelevant voxels for a given set of stimuli

Decoding the Formation of New Semantics: MVPA Investigation of Rapid Neocortical Plasticity during Associative Encoding through Fast Mapping

Neocortical structures typically only support slow acquisition of declarative memory; however, learning through fast mapping may facilitate rapid learning-induced cortical plasticity and hippocampal-independent integration of novel associations into existing semantic networks. During fast mapping the meaning of new words and concepts is inferred, and durable novel associations are incidentally formed, a process thought to support early childhood’s exuberant learning. The anterior temporal lobe, a cortical semantic memory hub, may critically support such learning. We investigated encoding of semantic associations through fast mapping using fMRI and multivoxel pattern analysis. Subsequent memory performance following fast mapping was more efficiently predicted using anterior temporal lobe than hippocampal voxels, while standard explicit encoding was best predicted by hippocampal activity. Searchlight algorithms revealed additional activity patterns that predicted successful fast mapping semantic learning located in lateral occipitotemporal and parietotemporal neocortex and ventrolateral prefrontal cortex. By contrast, successful explicit encoding could be classified by activity in medial and dorsolateral prefrontal and parahippocampal cortices. We propose that fast mapping promotes incidental rapid integration of new associations into existing neocortical semantic networks by activating related, nonoverlapping conceptual knowledge. In healthy adults, this is better captured by unique anterior and lateral temporal lobe activity patterns, while hippocampal involvement is less predictive of this kind of learning

One-Class SVMs for Document Classification

We implemented versions of the SVM appropriate for one-class classification in the context of information retrieval. The experiments were conducted on the standard Reuters data set. For the SVM implementation we used both a version of Schölkopf et al. and a somewhat different version of one-class SVM based on identifying “outlier ” data as representative of the second-class. We report on experiments with different kernels for both of these implementations and with different representations of the data, including binary vectors, tf-idf representation and a modification called “Hadamard ” representation. Then we compared it with one-class versions of the algorithms prototype (Rocchio), nearest neighbor, naive Bayes, and finally a natural one-class neural network classification method based on “bottleneck” compression generated filters. The SVM approach as represented by Schölkopf was superior to all the methods except the neural network one, where it was, although occasionally worse, essentially comparable. However, the SVM methods turned out to be quite sensitive to the choice of representation and kernel in ways which are not well understood; therefore, for the time being leaving the neural network approach as the most robust