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.

Genome-Wide Analysis of Differentially Expressed Genes During the Early Stages of Tomato Infection by a Potyvirus

Plant responses against pathogens cause up-and downward shifts in gene expression. To identify differentially expressed genes in a plant-virus interaction, susceptible tomato plants were inoculated with the potyvirus Pepper yellow mosaic virus (PepYMV) and a subtractive library was constructed from inoculated leaves at 72 h after inoculation. Several genes were identified as upregulated, including genes involved in plant defense responses (e. g., pathogenesis-related protein 5), regulation of the cell cycle (e. g., cytokinin-repressed proteins), signal transduction (e. g., CAX-interacting protein 4, SNF1 kinase), transcriptional regulators (e. g., WRKY and SCARECROW transcription factors), stress response proteins (e. g., Hsp90, DNA-J, 20S proteasome alpha subunit B, translationally controlled tumor protein), ubiquitins (e. g., polyubiquitin, ubiquitin activating enzyme 2), among others. Downregulated genes were also identified, which likewise display identity with genes involved in several metabolic pathways. Differential expression of selected genes was validated by macroarray analysis and quantitative real-time polymerase chain reaction. The possible roles played by some of these genes in the viral infection cycle are discussed.

New primers for the amplification and sequencing of nuclear loci in a taxonomically wide set of reptiles and amphibians

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

A Genome-wide Screen for Neurospora crassa Transcription Factors Regulating Glycogen Metabolism

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

A low-voltage wide-swing programmable-gain current amplifier

A CMOS low-voltage, wide-swing continuous-time current amplifier is presented. Exhibiting an open-loop architecture, the circuit is composed of transresistance and transconductance stages built upon triode-operating transistors. In addition to an extended dynamic range, the current gain can be programmed within good accuracy by a rapport involving only transistor geometries and tuning biases. Low temperature-drift on gain setting is then expected.In accordance with a 0.35 mum n-well CMOS fabrication process and a single 1.1 V-supply, a balanced current-amplifier is designed for a programmable gain-range of 6 - 34 dB and optimized with respect to dynamic range. Simulated results from PSPICE and Bsim3v3 models indicate, for a 100 muA(pp)-output current, a THD of 0.96 and 1.87% at 1 KHz and 100 KHz, respectively. Input noise is 120 pArootHz @ 10 Hz, with S/N = 63.2 dB @ 1%-THD. At maximum gain, total quiescent consumption is 334 muW. Measurements from a prototyped amplifier reveal a gain-interval of 4.8-33.1 dB and a maximum current swing of 120 muA(pp). The current-amplifier bandwidth is above 1 MHz.

Many-body effects in wide parabolic AlGaAs quantum wells

Photoluminescence measurements at different temperatures have been performed to investigate the optical response of a two-dimensional electron gas in n-type wide parabolic quantum wells. A series of samples with different well widths in the range of 1000-3000 A was analyzed. Many-body effects, usually observed in the recombination process of a two-dimensional electron gas, appear as a strong enhancement in the photoluminescence spectra at the Fermi level at low temperature only in the thinnest parabolic quantum wells. The suppression of the many-body effect in the thicker quantum wells was attributed to the decrease of the overlap between the wavefunctions of the photocreated holes and the two-dimensional electrons belonging to the highest occupied electron subband. (C) 2007 American Institute of Physics.

The ribs of Eupatorieae (Asteraceae): of wide taxonomic value or reliable characters only among certain groups?

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Reductions in the Prevalence and Incidence of Geohelminth Infections following a City-wide Sanitation Program in a Brazilian Urban Centre

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Wide localized solitons in systems with time- and space-modulated nonlinearities

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Comparing river basins world-wide and contrasting inland fisheries in Africa and Central Amazonia

An analysis of covariance relating basin area (A, km2) to river length (L, km) and discharge rate (D, m3 s-1) was performed for two continents and showed that the two covariates (L and D) were highly significant and that the strength of the relationship changed between continents. For comparison, D was excluded but the result remained the same. Although geomorphological models are useful for establishing global levels of production, these regressions should be applied with caution. Historically, simple statistical models were developed to predict fish catches in rivers. These, based upon regression of catches on channel length or basin area for Africa and Central Amazonia, are contrasted in this paper because of their generally similar approach.

Prospective analysis about the world wide strategy of commercial vehicles development

The main objective of this paper is to make a prospective analysis about the tendencies of the world wide strategies of commercial vehicles development, in relation of the current local and international scenery. It has been done a research by using the Delphi method, which consists into regulate, systematically, the presentation of questions about a specified problem to a group of specialists. In order to guarantee more representative data, it has been adopted three distinct groups: academics, OEMs managers and Tier 1 suppliers managers. The results showed that the three mentioned groups have similar opinion about the necessity of having a product development in the subsidiaries companies; also it has been pointed the necessity of having more taylor made vehicles, due to the intrinsic characteristics of this industry segment. Copyright © 2008 SAE International.

Excitons in undoped AlGaAs/GaAs wide parabolic quantum wells

In this work the electronic structure of undoped AlGaAs/GaAs wide parabolic quantum wells (PQWs) with different well widths (1000 and 3000 ) were investigated by means of photoluminescence (PL) measurements. Due to the particular potential shape, the sample structure confines photocreated carriers with almost three-dimensional characteristics. Our data show that depending on the well width thickness it is possible to observe very narrow structures in the PL spectra, which were ascribed to emissions associated to the recombination of confined 1s-excitons of the parabolic potential wells. From our measurements, the exciton binding energies (of a few meV) were estimated. Besides the exciton emission, we have also observed PL emissions associated to electrons in the excited subbands of the PQWs. © 2010 IOP Publishing Ltd.

Determination of copper at wide range concentrations using instrumental features of high-resolution continuum source flame atomic absorption spectrometry

This work describes a method to determine Cu at wide range concentrations in a single run without need of further dilutions employing high-resolution continuum source flame atomic absorption spectrometry. Different atomic lines for Cu at 324. 754 nm, 327. 396 nm, 222. 570 nm, 249. 215 nm and 224. 426 nm were evaluated and main figures of merit established. Absorbance measurements at 324. 754 nm, 249. 215 nm and 224. 426 nm allows the determination of Cu in the 0. 07-5. 0 mg L -1, 5. 0-100 mg L -1 and 100-800 mg L -1 concentration intervals respectively with linear correlation coefficients better than 0. 998. Limits of detection were 21 μg L -1, 310 μg L -1 and 1400 μg L -1 for 324. 754 nm, 249. 215 nm and 224. 426 nm, respectively and relative standard deviations (n = 12) were ≤ 2. 7%. The proposed method was applied to water samples spiked with Cu and the results were in agreement at a 95% of confidence level (paired t-test) with those obtained by line-source flame atomic absorption spectrometry.

Fractional order and dynamic simulation of a system involving an elastic wide plate

Numerous researchers have studied about nonlinear dynamics in several areas of science and engineering. However, in most cases, these concepts have been explored mainly from the standpoint of analytical and computational methods involving integer order calculus (IOC). In this paper we have examined the dynamic behavior of an elastic wide plate induced by two electromagnets of a point of view of the fractional order calculus (FOC). The primary focus of this study is on to help gain a better understanding of nonlinear dynamic in fractional order systems. © 2011 American Institute of Physics.

Genome-Wide Analysis Reveals Selection for Important Traits in Domestic Horse Breeds

Intense selective pressures applied over short evolutionary time have resulted in homogeneity within, but substantial variation among, horse breeds. Utilizing this population structure, 744 individuals from 33 breeds, and a 54,000 SNP genotyping array, breed-specific targets of selection were identified using an FST-based statistic calculated in 500-kb windows across the genome. A 5.5-Mb region of ECA18, in which the myostatin (MSTN) gene was centered, contained the highest signature of selection in both the Paint and Quarter Horse. Gene sequencing and histological analysis of gluteal muscle biopsies showed a promoter variant and intronic SNP of MSTN were each significantly associated with higher Type 2B and lower Type 1 muscle fiber proportions in the Quarter Horse, demonstrating a functional consequence of selection at this locus. Signatures of selection on ECA23 in all gaited breeds in the sample led to the identification of a shared, 186-kb haplotype including two doublesex related mab transcription factor genes (DMRT2 and 3). The recent identification of a DMRT3 mutation within this haplotype, which appears necessary for the ability to perform alternative gaits, provides further evidence for selection at this locus. Finally, putative loci for the determination of size were identified in the draft breeds and the Miniature horse on ECA11, as well as when signatures of selection surrounding candidate genes at other loci were examined. This work provides further evidence of the importance of MSTN in racing breeds, provides strong evidence for selection upon gait and size, and illustrates the potential for population-based techniques to find genomic regions driving important phenotypes in the modern horse. © 2013 Petersen et al.