A machine learning approach for genome-wide prediction of morbid and druggable human genes based on systems-level data

Background: The genome-wide identification of both morbid genes, i.e., those genes whose mutations cause hereditary human diseases, and druggable genes, i.e., genes coding for proteins whose modulation by small molecules elicits phenotypic effects, requires experimental approaches that are time-consuming and laborious. Thus, a computational approach which could accurately predict such genes on a genome-wide scale would be invaluable for accelerating the pace of discovery of causal relationships between genes and diseases as well as the determination of druggability of gene products.Results: In this paper we propose a machine learning-based computational approach to predict morbid and druggable genes on a genome-wide scale. For this purpose, we constructed a decision tree-based meta-classifier and trained it on datasets containing, for each morbid and druggable gene, network topological features, tissue expression profile and subcellular localization data as learning attributes. This meta-classifier correctly recovered 65% of known morbid genes with a precision of 66% and correctly recovered 78% of known druggable genes with a precision of 75%. It was than used to assign morbidity and druggability scores to genes not known to be morbid and druggable and we showed a good match between these scores and literature data. Finally, we generated decision trees by training the J48 algorithm on the morbidity and druggability datasets to discover cellular rules for morbidity and druggability and, among the rules, we found that the number of regulating transcription factors and plasma membrane localization are the most important factors to morbidity and druggability, respectively.Conclusions: We were able to demonstrate that network topological features along with tissue expression profile and subcellular localization can reliably predict human morbid and druggable genes on a genome-wide scale. Moreover, by constructing decision trees based on these data, we could discover cellular rules governing morbidity and druggability.

Transducer Loading Effect on the Performance of PZT-Based SHM Systems

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Optimal Frequency Range Selection for PZT Transducers in Impedance-Based SHM Systems

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

A comparative study of thermal conductivity in ZnO- and SnO2-based varistor systems

We performed a comparative study of electrical and thermal properties of ZnO- and SnO2-based varistor. The electrical properties of commercial ZnO-based varistor are equivalent to that found in SnO2-based varistor system. In spite of this, the SnO2 showed a thermal conductivity higher than commercial samples of ZnO-based varistor, which allied with its simpler microstructure and lower dopant concentration is a remarkable result that point out to the use of this system to compete commercially with ZnO-based varistor devices.

MnO2 influence on the electrical properties of SnO2-based ceramic systems

Tin dioxide is an n-type semiconductor that when doped with other metallic oxides exhibits non-linear electric behavior with high non-linear coefficient values typical of a varistor. In this work, electrical properties of the SnO2.CoO.Ta2O5 and SnO2.CoO.MnO2.Ta2O5 ceramics systems were studied with the objective of analyzing the influence of MnO2 on sintering behavior and electrical properties of these systems. The compacts were prepared by powder mixture process and sintered at 1300°C for 1 hour, in air, using a constant heating rate of 10°C/min. The morphological and structural properties were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The densities of the sintered ceramics were measured using the Archimedes method. The SnO2.CoO.Ta2O5 and SnO2.CoO.MnO2.Ta2O5 systems presented breakdown fields (Eb) about 3100 V.cm-1 and 3800 V.cm-1, respectively, and non-linear coefficient (α) about 10 and 20, respectively.

Experimental analysis of the effect of the structure area on the PZT-based SHM systems

The structural health monitoring (SHM) systems based on electromechanical (E/M) impedance technique have been widely investigated. Although many studies indicate the reliability of this technique, some practical considerations still have to be considered in real applications. This paper presents an experimental analysis of the effect of the structure area on the system's performance. The results indicate that the sensitivity of the system to detect damage decreases significantly when the host structure has large cross-section area. Copyright © 2009 by ASME.

On the Chaotic Suppression of Both Ideal and Non-ideal Duffing Based Vibrating Systems, Using a Magnetorheological Damper

In this paper the dynamics of the ideal and non-ideal Duffing oscillator with chaotic behavior is considered. In order to suppress the chaotic behavior and to control the system, a control signal is introduced in the system dynamics. The control strategy involves the application of two control signals, a nonlinear feedforward control to maintain the controlled system in a periodic orbit, obtained by the harmonic balance method, and a state feedback control, obtained by the state dependent Riccati equation, to bring the system trajectory into the desired periodic orbit. Additionally, the control strategy includes an active magnetorheological damper to actuate on the system. The control force of the damper is a function of the electric current applied in the coil of the damper, that is based on the force given by the controller and on the velocity of the damper piston displacement. Numerical simulations demonstrate the effectiveness of the control strategy in leading the system from any initial condition to a desired orbit, and considering the mathematical model of the damper (MR), it was possible to control the force of the shock absorber (MR), by controlling the applied electric current in the coils of the damper. © 2012 Foundation for Scientific Research and Technological Innovation.

In silico network topology-based prediction of gene essentiality

The identification of genes essential for survival is important for the understanding of the minimal requirements for cellular life and for drug design. As experimental studies with the purpose of building a catalog of essential genes for a given organism are time-consuming and laborious, a computational approach which could predict gene essentiality with high accuracy would be of great value. We present here a novel computational approach, called NTPGE (Network Topology-based Prediction of Gene Essentiality), that relies on the network topology features of a gene to estimate its essentiality. The first step of NTPGE is to construct the integrated molecular network for a given organism comprising protein physical, metabolic and transcriptional regulation interactions. The second step consists in training a decision-tree-based machine-learning algorithm on known essential and non-essential genes of the organism of interest, considering as learning attributes the network topology information for each of these genes. Finally, the decision-tree classifier generated is applied to the set of genes of this organism to estimate essentiality for each gene. We applied the NTPGE approach for discovering the essential genes in Escherichia coli and then assessed its performance. (C) 2007 Elsevier B.V. All rights reserved.

Design and Characterization of Silicone and Surfactant Based Systems for Topical Drug Delivery

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The influence of area/volume ratio on microstructure and non-Ohmic properties of SnO2-based varistor ceramic blocks

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influence of Excitation Signal on Impedance-based Structural Health Monitoring

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Effect of oxidizing and reducing atmospheres on the electrical properties of dense SnO2-based varistors

The SnO2 based varistor systems recently presented in the literature appear to have a promising potential in commercial applications. Experimental evidence shows that there is a dependence of nonlinear constant values with thermal treatment under different atmospheres. Thermal treatments in oxygen and nitrogen rich atmospheres at 900 degreesC prove this dependence, indicating that the nonlinear constant values are significantly lower when the material is submitted to a nitrogen atmosphere. Moreover, electrical properties can be restored when the varistor is subjected to thermal treatment at the same temperature in an oxygen atmosphere, indicating that the mechanism seems to be reversible. This paper discusses this behavior focusing in the grain boundary region. Ta2O5 mol% concentrations are also analyzed and the results indicate an optimum Ta2O5 concentration of 0.05 mol% for the electrical properties (alpha = 44 and E-B = 6150 V cm(-1)). (C) 2001 Elsevier B.V. Ltd. All rights reserved.

Thermal conductivity features of ZnO-based varistors using the laser-pulse method

The thermal conductivity of several commercial ZnO-based varistor systems was determined based on the laser-pulse method, a technique that proved extremely useful and easy to apply. Using this technique, the thermal conductivity was found to be dependent on the microstructural features of the devices, involving the mean grain size and phase composition. Among the phases existing in commercial ZnO-based varistors, ZniSb2O12 and Bi2O3 were found to contribute strongly to the thermal conductivity of the devices. (C) 2003 Elsevier B.V. All rights reserved.

Proposal of convergence of e-Learning systems for t-Learning

This article presents considerations about viability on reutilize existing web based e-Learning systems on Interactive Digital TV environment according to Digital TV standard adopted in Brazil. Considering the popularity of Moodle system in academic and corporative area, such system was chosen as a foundation for a survey into its properties to create a specification of an Application Programming Interface (API) for convergence to t-Learning characteristics that demands efforts in interface design area due the fact that computer and TV concepts are totally different. This work aims to present studies concerning user interface design during two stages: survey and detail of functionalities from an e-Learning system and how to adapt them for the Interactive TV regarding usability context and Information Architecture concepts.

Variação genética em progênies de jacaranda cuspidifolia mart. Utilizando o delineamento sistemático tipo leque

Knowledge of genetic variation in native tree species has helped direct strategies of genetic ex situ conservation, based on provenances and progenies tests. These tests use fixed spacing, not allowing evaluating the behavior of different progenies under this management variable. One way to evaluate simultaneously the genetic variation and different spacing in a small planting area is to use a systematic design. The aim of this study was to estimate the genetic variation and to evaluate its performance in Jacaranda cuspidifolia under different spacing. We used a progeny test in a systematic fan design, arranged in a system of 30 concentric rays, with one progeny per ray, randomly, at angles of 12°. The plants were arranged in rays in geometric progression of ratio 1.21, corresponding to nine for plant spacing: 1,95 m2; 2,86 m2; 4,18 m2; 6,12 m2; 8,96 m2; 13,12 m2; 19,21 m2; 28,13 m2; e 41,19 m 2 installed in Selvíria/MS. The traits height, height diameter of 30 cm to soil (DA3) and survival were evaluated at 12 and 24 months of age. Estimates of genetic parameters and spacing were evaluated using the procedure REML/BLUP (restricted maximum likelihood / best linear unbiased prediction). The progenies showed genetic variation, showing that the sample strategy to ex situ conservation was efficient. The species showed good adaptability inthe field and the best performance in treating five, equivalent to a 3 × 3 m spacing, with 8,96 m2;/plant for all traits. The fan systematic design permitted to evaluate in a small area the silvicultural behavior of J. Cuspidifolia plants in spacing varying from 2 to 42 m2/plant (5.000 to 238 trees/ha); which could hardly be evaluat by the traditional designs.