Reverse Engineering Gene Networks with ANN: Variability in Network Inference Algorithms

Motivation :Reconstructing the topology of a gene regulatory network is one of the key tasks in systems biology. Despite of the wide variety of proposed methods, very little work has been dedicated to the assessment of their stability properties. Here we present a methodical comparison of the performance of a novel method (RegnANN) for gene network inference based on multilayer perceptrons with three reference algorithms (ARACNE, CLR, KELLER), focussing our analysis on the prediction variability induced by both the network intrinsic structure and the available data. Results: The extensive evaluation on both synthetic data and a selection of gene modules of "Escherichia coli" indicates that all the algorithms suffer of instability and variability issues with regards to the reconstruction of the topology of the network. This instability makes objectively very hard the task of establishing which method performs best. Nevertheless, RegnANN shows MCC scores that compare very favorably with all the other inference methods tested. Availability: The software for the RegnANN inference algorithm is distributed under GPL3 and it is available at the corresponding author home page (http://mpba.fbk.eu/grimaldi/regnann-supmat

A molecular and parasitological survey of Hepatozoon canis in domestic dogs in Turkey

In this study, asymptomatic dogs in nine provinces of Turkey were surveyed to investigate the prevalence and intensity of Hepatozoon canis infection. DNA obtained from blood samples collected from 694 domestic dogs (243 stray, 288 shelter, and 163 pets) of both genders and varying ages were evaluated by polymerase chain reaction (PCR). In addition, 285 thin blood smears prepared from these blood samples were also evaluated for microscopic examination. Direct microscopy revealed Hepatozoon gamonts in the peripheral blood of three of 285 (1.0%; 95% confidence interval (CI): 0.21–3.04) tested. Using PCR, 155 of the 694 (22.3%; 95% CI: 19.28–25.61) were found to be positive for the presence of H. canis DNA. The prevalence of infection was higher in adult dogs (26.2%; 95% CI: 22.1–30.7) than young animals (16.4%; 95% CI: 12.2–21.3). Although the prevalence determined by PCR was higher in male dogs (24.5%; 95% CI: 19.6–29.9) than in female dogs (20.8%; 95% CI: 16.9–25.1), gender differences were not significant. Pet dogs had a lower prevalence of infection (10.4%; 95% CI: 6.2–16.2) compared to stray (26.3%; 95% CI: 20.9–32.3) and shelter dogs (25.7%; 95% CI: 20.7–31.1), but no significant association between stray and shelter dogs was found for the presence of the parasite. Partial sequences of the 18S ribosomal RNA (rRNA) gene shared 99–100% similarity with the corresponding H. canis isolates. This epidemiological survey revealed a high prevalence of H. canis in dogs from several provinces in Turkey, and it suggests that the age and origin are associated with the parasite

The escape of ionising radiation from high-redshift dwarf galaxies

The UV escape fraction from high-redshift galaxies plays a key role in models of cosmic reionisation. Because it is currently not possible to deduce the escape fractions during the epoch of reionisation from observations, we have to rely on numerical simulations. Our aim is to better constrain the escape fraction from high-redshift dwarf galaxies, as these are the most likely sources responsible for reionising the Universe. We employ a N-body/SPH method that includes realistic prescriptions for the physical processes that are important for the evolution of dwarf galaxies. These models are post-processed with radiative transfer to determine the escape fraction of ionising radiation. We perform a parameter study to assess the influence of the spin parameter, gas fraction and formation redshift of the galaxy and study the importance of numerical parameters as resolution, source distribution and local gas clearing. We find that the UV escape fraction from high-redshift dwarf galaxies that have formed a rotationally supported disc lie between 1e-5 and 0.1. The mass and angular momentum of the galaxy are the most important parameters that determine the escape fraction. We compare our results to previous work and discuss the uncertainties of our models. The low escape fraction we find for high-redshift dwarf galaxies is balanced by their high stellar content, resulting in an efficiency parameter for stars that is only marginally lower than the values found by semi-analytic models of reionisation. We therefore conclude that dwarf galaxies play an important role in cosmic reionisation also after the initial starburst phase, when the gas has settled into a disc.Comment: 19 pages, 14 figures. Accepted for publication in A&

Molecular detection of tick-borne rickettsial and protozoan pathogens in domestic dogs from Turkey

Background: Canine tick-borne parasites have emerged in recent years, showing a wider geographic distribution and increased global prevalence. In addition to their veterinary importance, domestic dogs play an important role in the transmission cycles of some agents by acting as reservoirs and sentinels. This study investigated Babesia, Theileria, Anaplasma, and Ehrlichia species in asymptomatic dogs in ten provinces of Turkey. Methods: DNA obtained from blood samples collected from 757 domestic dogs (243 stray, 351 shelter, 163 pet) of both sexes and various ages were evaluated using PCR and reverse line blotting (RLB) assays. Results: Of the 757 dogs tested, 41 (5.4%) were found to be infected with one or more parasites. Ehrlichia canis (37/757, 4.9%) was the most common canine tick-borne pathogen, followed by Anaplasma platys (4/757, 0.5%). Babesia canis and Theileria annulata were each detected in 1 (0.13%) sample. Combined infection of E. canis and A. platys was detected in 2 (0.3%) samples. The prevalence of tick-borne pathogens was higher in adult dogs (6.8%) than in those under one year old (3.1%). Difference in infection rate of male and female dogs was not significant. Pet dogs had a lower prevalence of infection (1.2%) compared to stray (7.4%) and shelter dogs (6%) although the difference between stray and shelter dogs was not significant. Conclusions: Babesia canis, T. annulata, A. platys, and E. canis species were identified at the molecular level in dogs in several provinces of Turkey, with E. canis being the most common species among tick-borne pathogens. Detailed studies should be conducted regarding the existence and prevalence of B. canis and Dermacentor reticulatus in eastern Turkey

The WiggleZ Dark Energy Survey: Direct constraints on blue galaxy intrinsic alignments at intermediate redshifts

Correlations between the intrinsic shapes of galaxy pairs, and between the intrinsic shapes of galaxies and the large-scale density field, may be induced by tidal fields. These correlations, which have been detected at low redshifts (z<0.35) for bright red galaxies in the Sloan Digital Sky Survey (SDSS), and for which upper limits exist for blue galaxies at z~0.1, provide a window into galaxy formation and evolution, and are also an important contaminant for current and future weak lensing surveys. Measurements of these alignments at intermediate redshifts (z~0.6) that are more relevant for cosmic shear observations are very important for understanding the origin and redshift evolution of these alignments, and for minimising their impact on weak lensing measurements. We present the first such intermediate-redshift measurement for blue galaxies, using galaxy shape measurements from SDSS and spectroscopic redshifts from the WiggleZ Dark Energy Survey. Our null detection allows us to place upper limits on the contamination of weak lensing measurements by blue galaxy intrinsic alignments that, for the first time, do not require significant model-dependent extrapolation from the z~0.1 SDSS observations. Also, combining the SDSS and WiggleZ constraints gives us a long redshift baseline with which to constrain intrinsic alignment models and contamination of the cosmic shear power spectrum. Assuming that the alignments can be explained by linear alignment with the smoothed local density field, we find that a measurement of \sigma_8 in a blue-galaxy dominated, CFHTLS-like survey would be contaminated by at most +/-0.02 (95% confidence level, SDSS and WiggleZ) or +/-0.03 (WiggleZ alone) due to intrinsic alignments. [Abridged]Comment: 18 pages, 12 figures, accepted to MNRAS; v2 has correction to one author's name, NO other changes; v3 has minor changes in explanation and calculations, no significant difference in results or conclusions; v4 has an additional footnote about model interpretation, no changes to data/calculations/result

Impact of antimicrobial drug restrictions on doctors' behaviors

Background/aim: Broad-spectrum antibiotics have become available for use only with the approval of infectious disease specialists (IDSs) since 2003 in Turkey. This study aimed to analyze the tendencies of doctors who are not disease specialists (non-IDSs) towards the restriction of antibiotics.Materials and methods: A questionnaire form was prepared, which included a total of 22 questions about the impact of antibiotic restriction (AR) policy, the role of IDSs in the restriction, and the perception of this change in antibiotic consumption. The questionnaire was completed by each participating physician.Results: A total of 1906 specialists from 20 cities in Turkey participated in the study. Of those who participated, 1271 (67.5%) had 5 years of occupational experience in their branch expressed that they followed the antibiotic guidelines more strictly than the JSs (P < 0.05) and 755 of physicians (88%) and 720 of surgeons (84.6%) thought that the AR policy was necessary and useful (P < 0.05).Conclusion: This study indicated that the AR policy was supported by most of the specialists. Physicians supported this restriction policy more so than surgeons did

GWAS study using DNA pooling strategy identifies association of variant rs4910623 in OR52B4 gene with anti-VEGF treatment response in age-related macular degeneration

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Pooled DNA based GWAS to determine genetic association of SNPs with visual acuity (VA) outcome in anti-vascular endothelial growth factor (anti-VEGF) treated neovascular age-related macular degeneration (nAMD) patients. We performed pooled DNA based GWAS on 285 anti-VEGF treated nAMD patients using high density Illumina 4.3 M array. Primary outcome was change in VA in Early Treatment Diabetic Retinopathy Study (ETDRS) letters after 6 months of anti-VEGF treatment (patients who lost ≥5 ETDRS letters classified as non-responders and all remaining classified as responders). GWAS analysis identified 44 SNPs of interest: 37 with strong evidence of association (p < 9 × 10−8), 2 in drug resistance genes (p < 5 × 10−6) and 5 nonsynonymous changes (p < 1 × 10−4). In the validation phase, individual genotyping of 44 variants showed three SNPs (rs4910623 p = 5.6 × 10−5, rs323085 p = 6.5 × 10−4 and rs10198937 p = 1.30 × 10−3) remained associated with VA response at 6 months. SNP rs4910623 also associated with treatment response at 3 months (p = 1.5 × 10−3). Replication of these three SNPs in 376 patients revealed association of rs4910623 with poor VA response after 3 and 6 months of treatment (p = 2.4 × 10−3 and p = 3.5 × 10−2, respectively). Meta-analysis of both cohorts (673 samples) confirmed association of rs4910623 with poor VA response after 3 months (p = 1.2 × 10−5) and 6 months (p = 9.3 × 10−6) of treatment in nAMD patients

Gas Accretion and Star Formation Rates

Cosmological numerical simulations of galaxy evolution show that accretion of metal-poor gas from the cosmic web drives the star formation in galaxy disks. Unfortunately, the observational support for this theoretical prediction is still indirect, and modeling and analysis are required to identify hints as actual signs of star-formation feeding from metal-poor gas accretion. Thus, a meticulous interpretation of the observations is crucial, and this observational review begins with a simple theoretical description of the physical process and the key ingredients it involves, including the properties of the accreted gas and of the star-formation that it induces. A number of observations pointing out the connection between metal-poor gas accretion and star-formation are analyzed, specifically, the short gas consumption time-scale compared to the age of the stellar populations, the fundamental metallicity relationship, the relationship between disk morphology and gas metallicity, the existence of metallicity drops in starbursts of star-forming galaxies, the so-called G dwarf problem, the existence of a minimum metallicity for the star-forming gas in the local universe, the origin of the alpha-enhanced gas forming stars in the local universe, the metallicity of the quiescent BCDs, and the direct measurements of gas accretion onto galaxies. A final section discusses intrinsic difficulties to obtain direct observational evidence, and points out alternative observational pathways to further consolidate the current ideas.Comment: Invited review to appear in Gas Accretion onto Galaxies, Astrophysics and Space Science Library, eds. A. J. Fox & R. Dav\'e, to be published by Springe

Observational Diagnostics of Gas Flows: Insights from Cosmological Simulations

Galactic accretion interacts in complex ways with gaseous halos, including galactic winds. As a result, observational diagnostics typically probe a range of intertwined physical phenomena. Because of this complexity, cosmological hydrodynamic simulations have played a key role in developing observational diagnostics of galactic accretion. In this chapter, we review the status of different observational diagnostics of circumgalactic gas flows, in both absorption (galaxy pair and down-the-barrel observations in neutral hydrogen and metals; kinematic and azimuthal angle diagnostics; the cosmological column density distribution; and metallicity) and emission (Lya; UV metal lines; and diffuse X-rays). We conclude that there is no simple and robust way to identify galactic accretion in individual measurements. Rather, progress in testing galactic accretion models is likely to come from systematic, statistical comparisons of simulation predictions with observations. We discuss specific areas where progress is likely to be particularly fruitful over the next few years.Comment: Invited review to appear in Gas Accretion onto Galaxies, Astrophysics and Space Science Library, eds. A. J. Fox & R. Dave, to be published by Springer. Typos correcte

Influence of Statistical Estimators of Mutual Information and Data Heterogeneity on the Inference of Gene Regulatory Networks

The inference of gene regulatory networks from gene expression data is a difficult problem because the performance of the inference algorithms depends on a multitude of different factors. In this paper we study two of these. First, we investigate the influence of discrete mutual information (MI) estimators on the global and local network inference performance of the C3NET algorithm. More precisely, we study different MI estimators (Empirical, Miller-Madow, Shrink and Schürmann-Grassberger) in combination with discretization methods (equal frequency, equal width and global equal width discretization). We observe the best global and local inference performance of C3NET for the Miller-Madow estimator with an equal width discretization. Second, our numerical analysis can be considered as a systems approach because we simulate gene expression data from an underlying gene regulatory network, instead of making a distributional assumption to sample thereof. We demonstrate that despite the popularity of the latter approach, which is the traditional way of studying MI estimators, this is in fact not supported by simulated and biological expression data because of their heterogeneity. Hence, our study provides guidance for an efficient design of a simulation study in the context of network inference, supporting a systems approach