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James Lowey

Publications and source records attributed to James Lowey.

4 recordsLinked to original sources

Noise-injected neural networks show promise for use on small-sample expression data.

BACKGROUND: Overfitting the data is a salient issue for classifier design in small-sample settings. This is why selecting a classifier from a constrained family of classifiers, ones that do not possess the potential to too finely partition the feature space, is typically preferable. But overfitting is not merely a consequence of the classifier family; it is highly dependent on the classification rule used to design a classifier from the sample data. Thus, it is possible to consider families that are rather complex but for which there are classification rules that perform well for small samples. Such classification rules can be advantageous because they facilitate satisfactory classification when the class-conditional distributions are not easily separated and the sample is not large. Here we consider neural networks, from the perspectives of classical design based solely on the sample data and from noise-injection-based design. RESULTS: This paper provides an extensive simulation-based comparative study of noise-injected neural-network design. It considers a number of different feature-label models across various small sample sizes using varying amounts of noise injection. Besides comparing noise-injected neural-network design to classical neural-network design, the paper compares it to a number of other classification rules. Our particular interest is with the use of microarray data for expression-based classification for diagnosis and prognosis. To that end, we consider noise-injected neural-network design as it relates to a study of survivability of breast cancer patients. CONCLUSION: The conclusion is that in many instances noise-injected neural network design is superior to the other tested methods, and in almost all cases it does not perform substantially worse than the best of the other methods. Since the amount of noise injected is consequential, the effect of differing amounts of injected noise must be considered.

Algorithms↗

Genetic test bed for feature selection.

MOTIVATION: Given a large set of potential features, such as the set of all gene-expression values from a microarray, it is necessary to find a small subset with which to classify. The task of finding an optimal feature set of a given size is inherently combinatoric because to assure optimality all feature sets of a given size must be checked. Thus, numerous suboptimal feature-selection algorithms have been proposed. There are strong impediments to evaluate feature-selection algorithms using real data when data are limited, a common situation in genetic classification. The difficulty is compound. First, there are no class-conditional distributions from which to draw data points, only a single small labeled sample. Second, there are no test data with which to estimate the feature-set errors, and one must depend on a training-data-based error estimator. Finally, there is no optimal feature set with which to compare the feature sets found by the algorithms. RESULTS: This paper describes a genetic test bed for the evaluation of feature-selection algorithms. It begins with a large biological feature-label dataset that is used as an empirical distribution and, using massively parallel computation, finds the top feature sets of various sizes based on a given sample size and classification rule. The user can draw random samples from the data, apply a proposed algorithm, and evaluate the proficiency of the proposed algorithm via three different measures (code provided). A key feature of the test bed is that, once a dataset is input, a single command creates the entire test bed relative to the dataset. The particular dataset used for the first version of the test bed comes from a microarray-based classification study that analyzes a large number of microarrays, prepared with RNA from breast tumor samples from each of 295 patients. AVAILABILITY: The software and supplementary material are available at http://public.tgen.org/tgen-cb/support/testbed/ CONTACT: edward@ece.tamu.edu.

Algorithms↗

The interaction of four genes in the inflammation pathway significantly predicts prostate cancer risk.

It is widely hypothesized that the interactions of multiple genes influence individual risk to prostate cancer. However, current efforts at identifying prostate cancer risk genes primarily rely on single-gene approaches. In an attempt to fill this gap, we carried out a study to explore the joint effect of multiple genes in the inflammation pathway on prostate cancer risk. We studied 20 genes in the Toll-like receptor signaling pathway as well as several cytokines. For each of these genes, we selected and genotyped haplotype-tagging single nucleotide polymorphisms (SNP) among 1,383 cases and 780 controls from the CAPS (CAncer Prostate in Sweden) study population. A total of 57 SNPs were included in the final analysis. A data mining method, multifactor dimensionality reduction, was used to explore the interaction effects of SNPs on prostate cancer risk. Interaction effects were assessed for all possible n SNP combinations, where n = 2, 3, or 4. For each n SNP combination, the model providing lowest prediction error among 100 cross-validations was chosen. The statistical significance levels of the best models in each n SNP combination were determined using permutation tests. A four-SNP interaction (one SNP each from IL-10, IL-1RN, TIRAP, and TLR5) had the lowest prediction error (43.28%, P = 0.019). Our ability to analyze a large number of SNPs in a large sample size is one of the first efforts in exploring the effect of high-order gene-gene interactions on prostate cancer risk, and this is an important contribution to this new and quickly evolving field.

Case-Control Studies↗

Optimal number of features as a function of sample size for various classification rules.

MOTIVATION: Given the joint feature-label distribution, increasing the number of features always results in decreased classification error; however, this is not the case when a classifier is designed via a classification rule from sample data. Typically (but not always), for fixed sample size, the error of a designed classifier decreases and then increases as the number of features grows. The potential downside of using too many features is most critical for small samples, which are commonplace for gene-expression-based classifiers for phenotype discrimination. For fixed sample size and feature-label distribution, the issue is to find an optimal number of features. RESULTS: Since only in rare cases is there a known distribution of the error as a function of the number of features and sample size, this study employs simulation for various feature-label distributions and classification rules, and across a wide range of sample and feature-set sizes. To achieve the desired end, finding the optimal number of features as a function of sample size, it employs massively parallel computation. Seven classifiers are treated: 3-nearest-neighbor, Gaussian kernel, linear support vector machine, polynomial support vector machine, perceptron, regular histogram and linear discriminant analysis. Three Gaussian-based models are considered: linear, nonlinear and bimodal. In addition, real patient data from a large breast-cancer study is considered. To mitigate the combinatorial search for finding optimal feature sets, and to model the situation in which subsets of genes are co-regulated and correlation is internal to these subsets, we assume that the covariance matrix of the features is blocked, with each block corresponding to a group of correlated features. Altogether there are a large number of error surfaces for the many cases. These are provided in full on a companion website, which is meant to serve as resource for those working with small-sample classification. AVAILABILITY: For the companion website, please visit http://public.tgen.org/tamu/ofs/ CONTACT: e-dougherty@ee.tamu.edu.

Algorithms↗