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Online prediction of onsets of seizure-like events in hippocampal neural networks using wavelet artificial neural networks.

It has been previously shown that wavelet artificial neural networks (WANNs) are able to classify the different states of epileptiform activity and predict the onsets of seizure-like events (SLEs) by offline processing (Ann. Biomed. Eng. 33(6):798-810, 2005) of the electrical data from the in-vitro hippocampal slice model of recurrent spontaneous SLEs. The WANN design entailed the assumption that time-varying frequency information from the biological recordings can be used to estimate the times at which onsets of SLEs would most likely occur in the future. Progressions of different frequency components were captured by the artificial neural network (ANN) using selective frequency inputs from the initial wavelet transform of the biological data. The training of the WANN had been established using 184 SLE episodes in 34 slices from 21 rats offline. Nine of these rats also exhibited periods of interictal bursts (IBs). These IBs were included as part of the training to help distinguish the difference in dynamics of bursting activities between the preictal- and interictal type. In this paper, we present the results of an online processing using WANN on 23 in-vitro rat hippocampal slices from 9 rats having 93 spontaneous SLE episodes generated under low magnesium conditions. Over the test cases, three of the nine rats exhibited over 30 min of IB activities. We demonstrated that the WANN was able to classify the different states, namely, interictal, preictal, ictal, and IB activities with an accuracy of 86.6, 72.6, 84.5, and 69.1%, respectively. Prediction of state transitions into ictal events was achieved using regression of initial "normalized time-to-onset" estimates. The SLE onsets can be estimated up to 36.4 s ahead of their actual occurrences, with a mean error of 14.3 +/- 27.0 s. The prediction errors decreased progressively as the actual time-to-onset decreased and more initial "normalized time-to-onset" estimates were used for the regression procedure.

Action Potentials↗

Gene name identification and normalization using a model organism database.

Biology has now become an information science, and researchers are increasingly dependent on expert-curated biological databases to organize the findings from the published literature. We report here on a series of experiments related to the application of natural language processing to aid in the curation process for FlyBase. We focused on listing the normalized form of genes and gene products discussed in an article. We broke this into two steps: gene mention tagging in text, followed by normalization of gene names. For gene mention tagging, we adopted a statistical approach. To provide training data, we were able to reverse engineer the gene lists from the associated articles and abstracts, to generate text labeled (imperfectly) with gene mentions. We then evaluated the quality of the noisy training data (precision of 78%, recall 88%) and the quality of the HMM tagger output trained on this noisy data (precision 78%, recall 71%). In order to generate normalized gene lists, we explored two approaches. First, we explored simple pattern matching based on synonym lists to obtain a high recall/low precision system (recall 95%, precision 2%). Using a series of filters, we were able to improve precision to 50% with a recall of 72% (balanced F-measure of 0.59). Our second approach combined the HMM gene mention tagger with various filters to remove ambiguous mentions; this approach achieved an F-measure of 0.72 (precision 88%, recall 61%). These experiments indicate that the lexical resources provided by FlyBase are complete enough to achieve high recall on the gene list task, and that normalization requires accurate disambiguation; different strategies for tagging and normalization trade off recall for precision.

Abstracting and Indexing↗

Topology of resultant networks shaped by evolutionary pressure.

Understanding the topology of complex systems abstracted to networks is important for unraveling their functional capabilities. Many such networks follow the small-world and scale-free regimes. Several models of artificially growing networks lead to this observed network topology. Most previously proposed models for growing networks, such as rich-get-richer and duplication-divergence, produce realistic network topologies but do not consider the effects of exogenous forces such as optimization for adaptation in shaping network topology. It is likely that such forces have shaped complex systems throughout their evolution. To develop further insights into possible mechanisms that shape networks, a model that uses several previously proposed network growth algorithms was developed to grow networks that adapt under exogenous stress. A decision tree problem was used to generate a complex Boolean function. Growing networks were required to adapt to correctly decode this function using an evolutionary selection process. Under this growth regimen all growing network models are similarly adaptable. The newly added nodes tend to cluster into pathways emanating from few inputs, regardless of the growth algorithm. Distribution of redundant pathways from inputs to the output follow a power-law function with a scaling exponent (approximately 1.3). Similar distribution of redundant pathways was observed from inputs in a cell signaling network and an air traffic control network. A flat distribution of redundant pathways from inputs was observed in growing networks that do not attempt to adapt. This analysis provides initial insights into distribution of pathways in naturally evolving complex systems that have defined input-output relationships.

Algorithms↗

Comparison of machine learning and traditional classifiers in glaucoma diagnosis.

Glaucoma is a progressive optic neuropathy with characteristic structural changes in the optic nerve head reflected in the visual field. The visual-field sensitivity test is commonly used in a clinical setting to evaluate glaucoma. Standard automated perimetry (SAP) is a common computerized visual-field test whose output is amenable to machine learning. We compared the performance of a number of machine learning algorithms with STATPAC indexes mean deviation, pattern standard deviation, and corrected pattern standard deviation. The machine learning algorithms studied included multilayer perceptron (MLP), support vector machine (SVM), and linear (LDA) and quadratic discriminant analysis (QDA), Parzen window, mixture of Gaussian (MOG), and mixture of generalized Gaussian (MGG). MLP and SVM are classifiers that work directly on the decision boundary and fall under the discriminative paradigm. Generative classifiers, which first model the data probability density and then perform classification via Bayes' rule, usually give deeper insight into the structure of the data space. We have applied MOG, MGG, LDA, QDA, and Parzen window to the classification of glaucoma from SAP. Performance of the various classifiers was compared by the areas under their receiver operating characteristic curves and by sensitivities (true-positive rates) at chosen specificities (true-negative rates). The machine-learning-type classifiers showed improved performance over the best indexes from STATPAC. Forward-selection and backward-elimination methodology further improved the classification rate and also has the potential to reduce testing time by diminishing the number of visual-field location measurements.

Artificial Intelligence↗

A hill-climbing approach for automatic gridding of cDNA microarray images.

Image and statistical analysis are two important stages of cDNA microarrays. Of these, gridding is necessary to accurately identify the location of each spot while extracting spot intensities from the microarray images and automating this procedure permits high-throughput analysis. Due to the deficiencies of the equipment used to print the arrays, rotations, misalignments, high contamination with noise and artifacts, and the enormous amount of data generated, solving the gridding problem by means of an automatic system is not trivial. Existing techniques to solve the automatic grid segmentation problem cover only limited aspects of this challenging problem and require the user to specify the size of the spots, the number of rows and columns in the grid, and boundary conditions. In this paper, a hill-climbing automatic gridding and spot quantification technique is proposed which takes a microarray image (or a subgrid) as input and makes no assumptions about the size of the spots, rows, and columns in the grid. The proposed method is based on a hill-climbing approach that utilizes different objective functions. The method has been found to effectively detect the grids on microarray images drawn from databases from GEO and the Stanford genomic laboratories.

Algorithms↗

Orthogonal laplacianfaces for face recognition.

Following the intuition that the naturally occurring face data may be generated by sampling a probability distribution that has support on or near a submanifold of ambient space, we propose an appearance-based face recognition method, called orthogonal Laplacianface. Our algorithm is based on the locality preserving projection (LPP) algorithm, which aims at finding a linear approximation to the eigenfunctions of the Laplace Beltrami operator on the face manifold. However, LPP is nonorthogonal, and this makes it difficult to reconstruct the data. The orthogonal locality preserving projection (OLPP) method produces orthogonal basis functions and can have more locality preserving power than LPP. Since the locality preserving power is potentially related to the discriminating power, the OLPP is expected to have more discriminating power than LPP. Experimental results on three face databases demonstrate the effectiveness of our proposed algorithm.

Algorithms↗

Dynamic model-based clustering for time-course gene expression data.

Microarray technology has produced a huge body of time-course gene expression data. Such gene expression data has proved useful in genomic disease diagnosis and genomic drug design. The challenge is how to uncover useful information in such data. Cluster analysis has played an important role in analyzing gene expression data. Many distance/correlation- and static model-based clustering techniques have been applied to time-course expression data. However, these techniques are unable to account for the dynamics of such data. It is the dynamics that characterize the data and that should be considered in cluster analysis so as to obtain high quality clustering. This paper proposes a dynamic model-based clustering method for time-course gene expression data. The proposed method regards a time-course gene expression dataset as a set of time series, generated by a number of stochastic processes. Each stochastic process defines a cluster and is described by an autoregressive model. A relocation-iteration algorithm is proposed to identity the model parameters and posterior probabilities are employed to assign each gene to an appropriate cluster. A bootstrapping method and an average adjusted Rand index (AARI) are employed to measure the quality of clustering. Computational experiments are performed on a synthetic and three real time-course gene expression datasets to investigate the proposed method. The results show that our method allows the better quality clustering than other clustering methods (e.g. k-means) for time-course gene expression data, and thus it is a useful and powerful tool for analyzing time-course gene expression data.

Algorithms↗

Quantitative prediction of mouse class I MHC peptide binding affinity using support vector machine regression (SVR) models.

BACKGROUND: The binding between peptide epitopes and major histocompatibility complex proteins (MHCs) is an important event in the cellular immune response. Accurate prediction of the binding between short peptides and the MHC molecules has long been a principal challenge for immunoinformatics. Recently, the modeling of MHC-peptide binding has come to emphasize quantitative predictions: instead of categorizing peptides as "binders" or "non-binders" or as "strong binders" and "weak binders", recent methods seek to make predictions about precise binding affinities. RESULTS: We developed a quantitative support vector machine regression (SVR) approach, called SVRMHC, to model peptide-MHC binding affinities. As a non-linear method, SVRMHC was able to generate models that out-performed existing linear models, such as the "additive method". By adopting a new "11-factor encoding" scheme, SVRMHC takes into account similarities in the physicochemical properties of the amino acids constituting the input peptides. When applied to MHC-peptide binding data for three mouse class I MHC alleles, the SVRMHC models produced more accurate predictions than those produced previously. Furthermore, comparisons based on Receiver Operating Characteristic (ROC) analysis indicated that SVRMHC was able to out-perform several prominent methods in identifying strongly binding peptides. CONCLUSION: As a method with demonstrated performance in the quantitative modeling of MHC-peptide binding and in identifying strong binders, SVRMHC is a promising immunoinformatics tool with not inconsiderable future potential.

Algorithms↗

Application of machine learning in SNP discovery.

BACKGROUND: Single nucleotide polymorphisms (SNP) constitute more than 90% of the genetic variation, and hence can account for most trait differences among individuals in a given species. Polymorphism detection software PolyBayes and PolyPhred give high false positive SNP predictions even with stringent parameter values. We developed a machine learning (ML) method to augment PolyBayes to improve its prediction accuracy. ML methods have also been successfully applied to other bioinformatics problems in predicting genes, promoters, transcription factor binding sites and protein structures. RESULTS: The ML program C4.5 was applied to a set of features in order to build a SNP classifier from training data based on human expert decisions (True/False). The training data were 27,275 candidate SNP generated by sequencing 1973 STS (sequence tag sites) (12 Mb) in both directions from 6 diverse homozygous soybean cultivars and PolyBayes analysis. Test data of 18,390 candidate SNP were generated similarly from 1359 additional STS (8 Mb). SNP from both sets were classified by experts. After training the ML classifier, it agreed with the experts on 97.3% of test data compared with 7.8% agreement between PolyBayes and experts. The PolyBayes positive predictive values (PPV) (i.e., fraction of candidate SNP being real) were 7.8% for all predictions and 16.7% for those with 100% posterior probability of being real. Using ML improved the PPV to 84.8%, a 5- to 10-fold increase. While both ML and PolyBayes produced a similar number of true positives, the ML program generated only 249 false positives as compared to 16,955 for PolyBayes. The complexity of the soybean genome may have contributed to high false SNP predictions by PolyBayes and hence results may differ for other genomes. CONCLUSION: A machine learning (ML) method was developed as a supplementary feature to the polymorphism detection software for improving prediction accuracies. The results from this study indicate that a trained ML classifier can significantly reduce human intervention and in this case achieved a 5-10 fold enhanced productivity. The optimized feature set and ML framework can also be applied to all polymorphism discovery software. ML support software is written in Perl and can be easily integrated into an existing SNP discovery pipeline.

Algorithms↗

Read Codes Version 3: a user led terminology.

Version 3 of the Read Codes was designed in response to a new set of requirements generated by three new terming initiatives in the UK, the Clinical Terms Project, the Professions Allied to Medicine Terms Project and the Nursing Terms Project. The challenge was to cope with the detail required by clinical specialists for maintaining a computerised record, to capture the natural language used by clinicians in their everyday work, and to support efficient analysis across medical records required to extract information from clinicians' individual patient data. The structure of Version 3 allows a directed acyclic graph to replace the traditional hierarchy; permits multiple such graphs if necessary; introduces qualifiers, embedding these in an information model to support analysis; introduces one-to-many mapping to external classifications where this is necessary; and maintains the tradition of a dynamic terminology that stresses the inclusion of natural clinical terms.

Artificial Intelligence↗

Evolving connectionist system versus algebraic formulas for prediction of renal function from serum creatinine.

BACKGROUND: In clinical trials, equation 7 from the Modification of Diet in Renal Disease (MDRD) Study is the most accurate formula for the prediction of glomerular filtration rate (GFR) from serum creatinine. An alternative approach has been developed using evolving connectionist systems (ECOS), which are novel computing structures that can be trained to generate accurate output from a given set of input variables. This study aims to compare the prediction errors associated with each method, using data that reproduce routine clinical practice as opposed to the artificial setting of clinical trials. METHODS: The methods were compared using 441 radioisotope measurements of GFR in 178 chronic kidney disease patients from 12 centers in Australia and New Zealand. All clinical and laboratory measurements were obtained from the patients' center rather than central laboratories, as would be the case in routine clinical practice. Both the MDRD formula and ECOS used the same predictive variables, and both were optimized to the study cohort by stepwise regression and training, respectively. RESULTS: Mean measured GFR in the cohort was 22.6 mL/min/1.73 m(2). The bias and precision of the MDRD formula were -3.5 mL/min/1.73 m(2) and 34.5%, respectively, improving to -1.2 mL/min/1.73 m(2) and 31.1% after maximal optimization of the formula to study data. The bias and precision of the ECOS were 0.7 mL/min/1.73 m(2) and 32.6%, respectively, improving to -0.1 mL/min/1.73 m(2) and 16.6% after maximal optimization of the system to study data. The prediction of GFR using ECOS was improved by accounting for the center from where clinical and laboratory measurements originated within the connectionist model. CONCLUSION: Algebraic formulas will be associated with greater prediction error in routine clinical practice than in the original trials, and machine intelligence is more likely to predict GFR accurately in this setting.

Adult↗

Combination of hyperbolic functions for multimodal biometrics data fusion.

In this paper, we treat the problem of combining fingerprint and speech biometric decisions as a classifier fusion problem. By exploiting the specialist capabilities of each classifier, a combined classifier may yield results which would not be possible in a single classifier. The Feedforward Neural Network provides a natural choice for such data fusion as it has been shown to be a universal approximator. However, the training process remains much to be a trial-and-error effort since no learning algorithm can guarantee convergence to optimal solution within finite iterations. In this work, we propose a network model to generate different combinations of the hyperbolic functions to achieve some approximation and classification properties. This is to circumvent the iterative training problem as seen in neural networks learning. In many decision data fusion applications, since individual classifiers or estimators to be combined would have attained a certain level of classification or approximation accuracy, this hyperbolic functions network can be used to combine these classifiers taking their decision outputs as the inputs to the network. The proposed hyperbolic functions network model is first applied to a function approximation problem to illustrate its approximation capability. This is followed by some case studies on pattern classification problems. The model is finally applied to combine the fingerprint and speaker verification decisions which show either better or comparable results with respect to several commonly used methods.

Algorithms↗

Learning eigenfunctions links spectral embedding and kernel PCA.

In this letter, we show a direct relation between spectral embedding methods and kernel principal components analysis and how both are special cases of a more general learning problem: learning the principal eigenfunctions of an operator defined from a kernel and the unknown data-generating density. Whereas spectral embedding methods provided only coordinates for the training points, the analysis justifies a simple extension to out-of-sample examples (the Nyström formula) for multidimensional scaling (MDS), spectral clustering, Laplacian eigenmaps, locally linear embedding (LLE), and Isomap. The analysis provides, for all such spectral embedding methods, the definition of a loss function, whose empirical average is minimized by the traditional algorithms. The asymptotic expected value of that loss defines a generalization performance and clarifies what these algorithms are trying to learn. Experiments with LLE, Isomap, spectral clustering, and MDS show that this out-of-sample embedding formula generalizes well, with a level of error comparable to the effect of small perturbations of the training set on the embedding.

Algorithms↗

Segmentation of trabeculated structures using an anisotropic Markov random field: application to the study of the optic nerve head in glaucoma.

The study of the architecture of the optic nerve head (ONH) may provide valuable information about the development and progression of glaucoma. To this end, we have generated three-dimensional datasets from monkey eyes under controlled intraocular pressure (IOP). Segmentation of the connective tissues in this area is crucial to obtain an accurate measurement of geometrical parameters and to build mechanical models. However, this segmentation is made difficult by the complicated geometry and the artifacts introduced in the dataset building process. We present a novel segmentation algorithm, based on expectation-maximization, which incorporates an anisotropic Markov random field (MRF) to introduce prior knowledge about the geometry of the structure. The structure tensor is used to characterize the predominant structure direction and the spatial coherence at each point. The algorithm, which has been validated on an artificial validation dataset that mimics our ONH datasets, shows significant improvement over an isotropic MRF. Results on the real datasets demonstrate the ability of the new algorithm to obtain accurate, spatially consistent segmentations of this structure.

Algorithms↗

Learning from noisy information in FasArt and FasBack neuro-fuzzy systems.

Neuro-fuzzy systems have been in the focus of recent research as a solution to jointly exploit the main features of fuzzy logic systems and neural networks. Within the application literature, neuro-fuzzy systems can be found as methods for function identification. This approach is supported by theorems that guarantee the possibility of representing arbitrary functions by fuzzy systems. However, due to the fact that real data are often noisy, generation of accurate identifiers is presented as an important problem. Within the Adaptive Resonance Theory (ART), PROBART architecture has been proposed as a solution to this problem. After a detailed comparison of these architectures based on their design principles, the FasArt and FasBack models are proposed. They are neuro-fuzzy identifiers that offer a dual interpretation, as fuzzy logic systems or neural networks. FasArt and FasBack can be trained on noisy data without need of change in their structure or data preprocessing. In the simulation work, a comparative study is carried out on the performances of Fuzzy ARTMAP, PROBART, FasArt and FasBack, focusing on prediction error and network complexity. Results show that FasArt and FasBack clearly enhance the performance of other models in this important problem.

Artifacts↗

A unified analysis of value-function-based reinforcement- learning algorithms.

Reinforcement learning is the problem of generating optimal behavior in a sequential decision-making environment given the opportunity of interacting with it. Many algorithms for solving reinforcement-learning problems work by computing improved estimates of the optimal value function. We extend prior analyses of reinforcement-learning algorithms and present a powerful new theorem that can provide a unified analysis of such value-function-based reinforcement-learning algorithms. The usefulness of the theorem lies in how it allows the convergence of a complex asynchronous reinforcement-learning algorithm to be proved by verifying that a simpler synchronous algorithm converges. We illustrate the application of the theorem by analyzing the convergence of Q-learning, model-based reinforcement learning, Q-learning with multistate updates, Q-learning for Markov games, and risk-sensitive reinforcement learning.

Algorithms↗

Perspectives on the use of chemometrics in laboratory medicine.

Today's automated laboratory instruments are capable of generating prodigious volumes of high-quality measurements. Increasingly, the powerful mathematical and statistical methods of chemometrics are being called upon to help reduce these measurements to useful information. Chemometric methods have been important in automating various data-intensive functions of the clinical laboratory, including analysis of cellular images, identification of bacteria and fungi on the basis of their metabolic and chemical properties, and identification of drugs and toxic substances from their mass spectra. These methods also appear promising in aiding both the selection and interpretation of laboratory tests for diagnosis, monitoring, and prognosis. In spite of the demonstrated potential of these methods, significant problems remain to be solved in the areas of measurement standardization, data-base collection, and user familiarity with these approaches before chemometric methods can be used most fully by the clinical laboratory.

Artificial Intelligence↗

Mining SARS-CoV protease cleavage data using non-orthogonal decision trees: a novel method for decisive template selection.

MOTIVATION: Although the outbreak of the severe acute respiratory syndrome (SARS) is currently over, it is expected that it will return to attack human beings. A critical challenge to scientists from various disciplines worldwide is to study the specificity of cleavage activity of SARS-related coronavirus (SARS-CoV) and use the knowledge obtained from the study for effective inhibitor design to fight the disease. The most commonly used inductive programming methods for knowledge discovery from data assume that the elements of input patterns are orthogonal to each other. Suppose a sub-sequence is denoted as P2-P1-P1'-P2', the conventional inductive programming method may result in a rule like 'if P1 = Q, then the sub-sequence is cleaved, otherwise non-cleaved'. If the site P1 is not orthogonal to the others (for instance, P2, P1' and P2'), the prediction power of these kind of rules may be limited. Therefore this study is aimed at developing a novel method for constructing non-orthogonal decision trees for mining protease data. RESULT: Eighteen sequences of coronavirus polyprotein were downloaded from NCBI (http://www.ncbi.nlm.nih.gov). Among these sequences, 252 cleavage sites were experimentally determined. These sequences were scanned using a sliding window with size k to generate about 50,000 k-mer sub-sequences (for short, k-mers). The value of k varies from 4 to 12 with a gap of two. The bio-basis function proposed by Thomson et al. is used to transform the k-mers to a high-dimensional numerical space on which an inductive programming method is applied for the purpose of deriving a decision tree for decision-making. The process of this transform is referred to as a bio-mapping. The constructed decision trees select about 10 out of 50,000 k-mers. This small set of selected k-mers is regarded as a set of decisive templates. By doing so, non-orthogonal decision trees are constructed using the selected templates and the prediction accuracy is significantly improved.

Algorithms↗