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A feed-forward network for input that is both categorical and quantitative.

The data on which a multi-layer perceptron (MLP) is to be trained to approximate a continuous function may have inputs that are categorical rather than numeric or quantitative such as color, gender, race, etc. A categorical variable causes a discontinuous relationship between an input variable and the output. A MLP, with connection matrices that multiply input values and sigmoid functions that further transform values, represents a continuous mapping in all input variables. A MLP therefore requires that all inputs correspond to numeric, continuously valued variables and represents a continuous function in all input variables. The way that this problem is usually dealt with is to replace the categorical values by numeric ones and treat them as if they were continuously valued. However, there is no meaningful correspondence between the continuous quantities generated this way and the original categorical values. Another approach is to encode the categorical portion of the input using 1-out-of-n encoding and include this code as input to the MLP. The approach in this paper is to segregate categorical variables from the continuous independent variables completely. The MLP is trained with multiple outputs; a separate output unit for each of the allowed combination of values of the categorical independent variables. During training the categorical value or combination of categorical values determines which of the output units should have the target value on it, with the remaining outputs being 'do not care'. Three data sets were used for comparison of methods. Results show that this approach is much more effective than the conventional approach of assigning continuous variables to the categorical features. In case of the data set where there were several categorical variables the method proposed here is also more effective than the 1-out-of-n input method.

Algorithms↗

Measurement of acoustic impedance and reflectance in the human ear canal.

The pressure reflectance R (omega) is the transfer function which may be defined for a linear one-port network by the ratio of the reflected complex pressure divided by the incident complex pressure. The reflectance is a function that is closely related to the impedance of the 1-port. The energy reflectance R (omega) is defined as magnitude of [R]2. It represents the ratio of reflected to incident energy. In the human ear canal the energy reflectance is important because it is a measure of the inefficiency of the middle ear and cochlea, and because of the insight provided by its simple frequency domain interpretation. One may characterize the ear canal impedance by use of the pressure reflectance and its magnitude, sidestepping the difficult problems of (a) the unknown canal length from the measurement point to the eardrum, (b) the complicated geometry of the drum, and (c) the cross-sectional area changes in the canal as a function of distance. Reported here are acoustic impedance measurements, looking into the ear canal, measured on ten young adults with normal hearing (ages 18-24). The measurement point in the canal was approximately 0.85 cm from the entrance of the canal. From these measurements, the pressure reflectance in the canal is computed and impedance and reflectance measurements from 0.1 to 15.0 kHz are compared among ears. The average reflectance and the standard deviation of the reflectance for the ten subjects have been determined. The impedance and reflectance of two common ear simulators, the Brüel & Kjaer 4157 and the Industrial Research Products DB-100 (Zwislocki) coupler are also measured and compared to the average human measurements. All measurements are made using controls that assure a uniform accuracy in the acoustic calibration across subjects. This is done by the use of two standard acoustic resistors whose impedances are known. From the experimental results, it is concluded that there is significant subject variability in the magnitude of the reflectance for the ten ear canals. This variability is believed to be due to cochlear and middle ear impedance differences. An attempt was made at modeling the reflectance but, as discussed in the paper, several problems presently stand in the way of these models. Such models would be useful for acoustic virtual-reality systems and for active noise control earphones.

Acoustic Impedance Tests↗

Prediction of O-glycosylation of mammalian proteins: specificity patterns of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase.

The specificity of the enzyme(s) catalysing the covalent link between the hydroxyl side chains of serine or threonine and the sugar moiety N-acetylgalactosamine (GalNAc) is unknown. Pattern recognition by artificial neural networks and weight matrix algorithms was performed to determine the exact position of in vivo O-linked GalNAc-glycosylated serine and threonine residues from the primary sequence exclusively. The acceptor sequence context for O-glycosylation of serine was found to differ from that of threonine and the two types were therefore treated separately. The context of the sites showed a high abundance of proline, serine and threonine extending far beyond the previously reported region covering positions -4 through +4 relative to the glycosylated residue. The O-glycosylation sites were found to cluster and to have a high abundance in the N-terminal part of the protein. The sites were also found to have an increased preference for three different classes of beta-turns. No simple consensus-like rule could be deduced for the complex glycosylation sequence acceptor patterns. The neural networks were trained on the hitherto largest data material consisting of 48 carefully examined mammalian glycoproteins comprising 264 O-glycosylation sites. For detection neural network algorithms were much more reliable than weight matrices. The networks correctly found 60-95% of the O-glycosylated serine/threonine residues and 88-97% of the non-glycosylated residues in two independent test sets of known glycoproteins. A computer server using E-mail for prediction of O-glycosylation sites has been implemented and made publicly available. The Internet address is NetOglyc@cbs.dtu.dk.

Algorithms↗

Functional consequences of an integration of motion and stereopsis in area MT of monkey extrastriate visual cortex.

Experimental evidence from neurophysiological recordings in the middle temporal (MT) area of the macaque monkey suggests that motion-selective cells can use disparity information to separate motion signals that originate from different depths. This finding of a cross-talk between different visual channels has implications for the understanding of the processing of motion in the primate visual system and especially for behavioral tasks requiring the determination of global motion. In this paper, the consequences for the analysis of optic flow fields are explored. A network model is presented that effectively uses the disparity sensitivity of MT-like neurons for the reduction of noise in optic flow fields. Simulations reproduce the recent psychophysical finding that the robustness of the human optic flow processing system is improved by stereoscopic depth information, but that the use of this information depends on the structure of the visual environment.

Animals↗

Hycones: a hybrid approach to designing decision support systems.

Hycones II is a tool that facilitates the construction of hybrid connectionist expert systems to solve problems in classification. Hycones II provides a hybrid system that integrates frames with three types of neural network: the "combinatorial" neural model (CNM), the "Fuzzy ARTMAP" model, and the "Semantic ART" (SMART) model, a combination of the CNM and Fuzzy ART-MAP. We will compare the ability of these three models to solve diagnostic problems in two medical domains.

Artificial Intelligence↗

Motor primitive and sequence self-organization in a hierarchical recurrent neural network.

This study describes how complex goal-directed behavior can be obtained through adaptation processes in a hierarchically organized recurrent neural network using a genetic algorithm (GA). Our experiments, using a simulated Khepera robot, showed that different types of dynamic structures self-organize in the lower and higher levels of the network for the purpose of achieving complex navigation tasks. The parametric bifurcation structures that appear in the lower level explain the mechanism of how behavior primitives are switched in a top-down way. In the higher level, a topologically ordered mapping of initial cell activation states to motor primitive sequences self-organizes by utilizing the initial sensitivity characteristics of non-linear dynamical systems. The biological plausibility of the model's essential principles is discussed.

Algorithms↗

Cortical instability and the mechanism of mania: a neural network simulation and perceptual test.

BACKGROUND: A previous neural network simulation suggested that manic states arise from excessive levels of noise that destabilize neural representations. The Necker cube stick figure provides a simple perceptual task that assesses stability of gestalt-type representations. METHODS: A neural network was developed that included a simulation of the Necker cube task. Noise was added to induce maniclike jumps from one representation to another. A parallel study of Necker cube perception was conducted with 16 patients diagnosed with manic-spectrum disorder, 18 patients with schizophrenia, and 19 normal control subjects. Cognitive speed and rate of indiscriminate responses were assessed using an auditory continuous performance task. RESULTS: During processing of the "Necker cube" stimulus, the reversal rate of the noise-destabilized "manic" network was increased by 30%. In the human subject study, the median score of Necker cube reversal rates for manic-spectrum patients was roughly twice that of normal control subjects and patients with schizophrenia. Accelerated reversal rates in the manic-spectrum group were not attributable to excessive cognitive speed or higher rates of indiscriminate responses. CONCLUSIONS: The two studies, considered together, support the hypothesis that excessive cortical noise destabilizes neural representations in manic-spectrum patients.

Adult↗

A method for diagnosing multiple diseases in MUNIN.

A new method for diagnosing multiple diseases in large medical decision support systems based on causal probabilistic networks is proposed. The method is based on characteristics of the diagnostic process that we believe to be present in many diagnostic tasks, both inside and outside medicine. The diagnosis must often be made under uncertainty, choosing between diagnoses that each have small prior probabilities, but not so small that the possibility of two or more simultaneous diseases can be ignored. Often a symptom can be caused by several diseases and the presence of several diseases tend to aggravate the symptoms. For diagnostic problems that share these characteristic, we have proposed a method that operates in a number of phases: in the first phase only single diseases are considered and this helps to focus the attention on a smaller number of plausible diseases. In the second phase, pairs of diseases are considered, which make it possible to narrow down the field of plausible diagnoses further. In the following phases, larger subsets of diseases are considered. The method was applied to the diagnosis of neuromuscular disorders, using previous experience with the so-called MUNIN system as a starting point. The results showed that the method gave large reductions in computation time without compromising the computational accuracy in any substantial way. It is concluded that the method enables practical inference in large medical expert systems based on causal probabilistic networks.

Decision Trees↗

An algorithm to assemble pathways from processes.

To understand or to modify a biological pathway, the first step is to determine the patterns of coupling among its processes that are compatible with its input-output relation. Algorithms for this purpose have been devised for metabolic pathways, in which the reactions typically leave the enzymes unmodified. As shown here, one of these algorithms can also assemble molecular networks in which reactions modify proteins, if the proteins are included among the inputs to the reactions. Thus one procedure suffices to assemble pathways for metabolism, cytoplasmic signal transduction, and gene regulation.

Algorithms↗

Interpreting spatial and temporal neural activity through a recurrent neural network brain-machine interface.

We propose the use of optimized brain-machine interface (BMI) models for interpreting the spatial and temporal neural activity generated in motor tasks. In this study, a nonlinear dynamical neural network is trained to predict the hand position of primates from neural recordings in a reaching task paradigm. We first develop a method to reveal the role attributed by the model to the sampled motor, premotor, and parietal cortices in generating hand movements. Next, using the trained model weights, we derive a temporal sensitivity measure to asses how the model utilized the sampled cortices and neurons in real-time during BMI testing.

Algorithms↗

Automatic spike detection via an artificial neural network using raw EEG data: effects of data preparation and implications in the limitations of online recognition.

OBJECTIVE: Automatic detection of epileptic EEG spikes via an artificial neural network has been reported to be feasible using raw EEG data as input. This study re-investigated its suitability by further exploring the effects of data preparation on classification performance testing. METHODS: Six hundred EEG files (300 spikes and 300 non-spikes) taken from 20 patients were included in this study. Raw EEG data were sent to the neural network using the architecture reported to give best performance (30 input-layer and 6 hidden-layer neurons). RESULTS: Significantly larger weighting of the 10th input-layer neuron was found after training with prepared raw EEG data. The classification process was thus dominated by the peak location. Subsequent analysis showed that online spike detection with an erroneously trained network yielded an area less than 0.5 under the receiver-operating-characteristic curve, and hence performed inferiorly to random assignments. Networks trained and tested using the same unprepared EEG data achieved no better than about 87% true classification rate at equal sensitivity and specificity. CONCLUSIONS: The high true classification rate reported previously is believed to be an artifact arising from erroneous data preparation and off-line validation. Spike detection using raw EEG data as input is unlikely to be feasible under current computer technology.

Brain↗

Qualitative analysis of gene networks.

In this paper, we review the qualitative tools developed by our group for the analysis of regulatory networks. Focusing on the dynamical and biological roles of feedback circuits, this method can be applied in the context of both logical and differential formalisms. This approach already led to several interesting results about the relation between the network structure and the corresponding dynamical properties. In particular, it could be shown that at least one positive regulatory circuit is necessary to generate multistationarity (i.e., alternative states of gene expression), whereas at least one negative circuit is necessary to generate a stable oscillatory behavior. Applications to the analysis of complex gene networks, as well as to the synthesis of regulatory models to account for global expression data are discussed.

Animals↗

PRED-CLASS: cascading neural networks for generalized protein classification and genome-wide applications.

A cascading system of hierarchical, artificial neural networks (named PRED-CLASS) is presented for the generalized classification of proteins into four distinct classes-transmembrane, fibrous, globular, and mixed-from information solely encoded in their amino acid sequences. The architecture of the individual component networks is kept very simple, reducing the number of free parameters (network synaptic weights) for faster training, improved generalization, and the avoidance of data overfitting. Capturing information from as few as 50 protein sequences spread among the four target classes (6 transmembrane, 10 fibrous, 13 globular, and 17 mixed), PRED-CLASS was able to obtain 371 correct predictions out of a set of 387 proteins (success rate approximately 96%) unambiguously assigned into one of the target classes. The application of PRED-CLASS to several test sets and complete proteomes of several organisms demonstrates that such a method could serve as a valuable tool in the annotation of genomic open reading frames with no functional assignment or as a preliminary step in fold recognition and ab initio structure prediction methods. Detailed results obtained for various data sets and completed genomes, along with a web sever running the PRED-CLASS algorithm, can be accessed over the World Wide Web at http://o2.biol.uoa.gr/PRED-CLASS.

Computational Biology↗

Classification of chromatic visual evoked potentials with the aid of a neural net.

Twelve normal subjects, and six color blind (three protanopes and three deuteranopes) individuals were used in this study. Visual evoked potentials (50-150 msec post-stimulus) were recorded in response to three stimuli: (a) three horizontal, achromatic bars alternating in luminosity between bright and dim, (b) bars alternating between blue and red, and (c) bars alternating between green and red. The resulting waveforms were normalized in amplitude and submitted to a commercial neural net program for classification. The network correctly identified 24 of the 36 normal responses. (2) The network was also asked to distinguish between the responses of normal and color blind individuals. Based upon the blue/red response, the network correctly classed 12 of 18 responses, and based upon the green/red response correctly classified 14 of 18 (including all 6 color blinds). (3) These results are statistically highly significant and suggest that the VEP elicited by chromatic stimulation is substantially different from that elicited by achromatic stimuli.

Classification↗

ARACNE: an algorithm for the reconstruction of gene regulatory networks in a mammalian cellular context.

BACKGROUND: Elucidating gene regulatory networks is crucial for understanding normal cell physiology and complex pathologic phenotypes. Existing computational methods for the genome-wide "reverse engineering" of such networks have been successful only for lower eukaryotes with simple genomes. Here we present ARACNE, a novel algorithm, using microarray expression profiles, specifically designed to scale up to the complexity of regulatory networks in mammalian cells, yet general enough to address a wider range of network deconvolution problems. This method uses an information theoretic approach to eliminate the majority of indirect interactions inferred by co-expression methods. RESULTS: We prove that ARACNE reconstructs the network exactly (asymptotically) if the effect of loops in the network topology is negligible, and we show that the algorithm works well in practice, even in the presence of numerous loops and complex topologies. We assess ARACNE's ability to reconstruct transcriptional regulatory networks using both a realistic synthetic dataset and a microarray dataset from human B cells. On synthetic datasets ARACNE achieves very low error rates and outperforms established methods, such as Relevance Networks and Bayesian Networks. Application to the deconvolution of genetic networks in human B cells demonstrates ARACNE's ability to infer validated transcriptional targets of the cMYC proto-oncogene. We also study the effects of misestimation of mutual information on network reconstruction, and show that algorithms based on mutual information ranking are more resilient to estimation errors. CONCLUSION: ARACNE shows promise in identifying direct transcriptional interactions in mammalian cellular networks, a problem that has challenged existing reverse engineering algorithms. This approach should enhance our ability to use microarray data to elucidate functional mechanisms that underlie cellular processes and to identify molecular targets of pharmacological compounds in mammalian cellular networks.

Algorithms↗

Bayesian probabilistic approach for predicting backbone structures in terms of protein blocks.

By using an unsupervised cluster analyzer, we have identified a local structural alphabet composed of 16 folding patterns of five consecutive C(alpha) ("protein blocks"). The dependence that exists between successive blocks is explicitly taken into account. A Bayesian approach based on the relation protein block-amino acid propensity is used for prediction and leads to a success rate close to 35%. Sharing sequence windows associated with certain blocks into "sequence families" improves the prediction accuracy by 6%. This prediction accuracy exceeds 75% when keeping the first four predicted protein blocks at each site of the protein. In addition, two different strategies are proposed: the first one defines the number of protein blocks in each site needed for respecting a user-fixed prediction accuracy, and alternatively, the second one defines the different protein sites to be predicted with a user-fixed number of blocks and a chosen accuracy. This last strategy applied to the ubiquitin conjugating enzyme (alpha/beta protein) shows that 91% of the sites may be predicted with a prediction accuracy larger than 77% considering only three blocks per site. The prediction strategies proposed improve our knowledge about sequence-structure dependence and should be very useful in ab initio protein modelling.

Artificial Intelligence↗

A computer model of rigidity and related motor dysfunction in Parkinson's disease.

This work explores the involvement of spinal circuits in the generation of parkinsonian rigidity and related motor dysfunction. A computer model of spinal proprioceptive input processing, derived from previous work on spasticity modeling, was adapted to the simulation of parkinsonian rigidity. Model parameters were varied to generate simulations reproducing experimental data obtained using the pendulum test of the leg in 10 parkinsonian patients and 3 healthy subjects. Convenient reproductions of experimental traces in rigidity were obtained by the combination of a low reflex gain and a decrease in reflex threshold. These findings are consistent with studies reporting an increase of spinal interneuron excitability and proprioception deficits in Parkinson's disease (PD). Moreover, as the threshold parameter was much lowered, our model generated typical features of parkinsonian resting tremor, endorsing the hypothesis of a participation of a spinal oscillator in this disorder. Finally, tuning the reflex gain during simulations of rigidity resulted in the generation of active movement, opening some hypotheses on pathophysiology of motor dysfunction in PD, and notably, of akinesia. More generally, this work accredits the hypothesis of the involvement of an aperiodic, altered supra-spinal motor drive in PD, resulting in spinal dysfunction, through specific descending motor pathways. This may lead to a search for new (spinal) pharmacological targets in PD. It emphasizes further the value of computer modeling in understanding motor control in health and disease.

Computer Simulation↗

Multiple approaches to data-mining of proteomic data based on statistical and pattern classification methods.

The data-mining challenge presented is composed of two fundamental problems. Problem one is the separation of forty-one subjects into two classifications based on the data produced by the mass spectrometry of protein samples from each subject. Problem two is to find the specific differences between protein expression data of two sets of subjects. In each problem, one group of subjects has a disease, while the other group is nondiseased. Each problem was approached with the intent to introduce a new and potentially useful tool to analyze protein expression from mass spectrometry data. A variety of methodologies, both conventional and nonconventional were used in the analysis of these problems. The results presented show both overlap and discrepancies. What is important is the breadth of the techniques and the future direction this analysis will create.

Artificial Intelligence↗