Reproducible computational biology experiments with SED-ML - The Simulation Experiment Description Markup Language

Background: The increasing use of computational simulation experiments to inform modern biological research creates new challenges to annotate, archive, share and reproduce such experiments. The recently published Minimum Information About a Simulation Experiment (MIASE) proposes a minimal set of information that should be provided to allow the reproduction of simulation experiments among users and software tools. Results: In this article, we present the Simulation Experiment Description Markup Language (SED-ML). SED-ML encodes in a computer-readable exchange format the information required by MIASE to enable reproduction of simulation experiments. It has been developed as a community project and it is defined in a detailed technical specification and additionally provides an XML schema. The version of SED-ML described in this publication is Level 1 Version 1. It covers the description of the most frequent type of simulation experiments in the area, namely time course simulations. SED-ML documents specify which models to use in an experiment, modifications to apply on the models before using them, which simulation procedures to run on each model, what analysis results to output, and how the results should be presented. These descriptions are independent of the underlying model implementation. SED-ML is a software-independent format for encoding the description of simulation experiments; it is not specific to particular simulation tools. Here, we demonstrate that with the growing software support for SED-ML we can effectively exchange executable simulation descriptions. Conclusions: With SED-ML, software can exchange simulation experiment descriptions, enabling the validation and reuse of simulation experiments in different tools. Authors of papers reporting simulation experiments can make their simulation protocols available for other scientists to reproduce the results. Because SED-ML is agnostic about exact modeling language(s) used, experiments covering models from different fields of research can be accurately described and combined

Chlorella Virus PBCV-1 Encodes a Functional Homospermidine Synthase

Sequence analysis of the 330-kb genome of chlorella virus Paramecium bursaria chlorella virus 1 (PBCV-1) revealed an open reading frame, A237R, that encodes a protein with 34% amino acid identity to homospermidine synthase from Rhodopseudomonas viridis. Expression of the a237r gene product in Escherichia coli established that the recombinant enzyme catalyzes the NAD+-dependent formation of homospermidine from two molecules of putrescine. The a237r gene is expressed late in PBCV-1 infection. Both uninfected and PBCV-1-infected chlorella, as well as PBCV-1 virions, contain homospermidine, along with the more common polyamines putrescine, spermidine, and cadaverine. The total number of polyamine molecules per virion (~539) is too small to significantly neutralize the virus double-stranded DNA (\u3e660,000 nucleotides). Consequently, the biological significance of the homospermidine synthase gene is unknown. However, the gene is widespread among the chlorella viruses. To our knowledge, this is the first report of a virus encoding an enzyme involved in polyamine biosynthesis

Pax6- and Six3-Mediated Induction of Lens Cell Fate in Mouse and Human ES Cells

Embryonic stem (ES) cells provide a potentially useful in vitro model for the study of in vivo tissue differentiation. We used mouse and human ES cells to investigate whether the lens regulatory genes Pax6 and Six3 could induce lens cell fate in vitro. To help assess the onset of lens differentiation, we derived a new mES cell line (Pax6-GFP mES) that expresses a GFP reporter under the control of the Pax6 P0 promoter and lens ectoderm enhancer. Pax6 or Six3 expression vectors were introduced into mES or hES cells by transfection or lentiviral infection and the differentiating ES cells analyzed for lens marker expression. Transfection of mES cells with Pax6 or Six3 but not with other genes induced the expression of lens cell markers and up-regulated GFP reporter expression in Pax6-GFP mES cells by 3 days post-transfection. By 7 days post-transfection, mES cell cultures exhibited a>10-fold increase over controls in the number of colonies expressing γA-crystallin, a lens fiber cell differentiation marker. RT-PCR and immunostaining revealed induction of additional lens epithelial or fiber cell differentiation markers including Foxe3, Prox1, α- and β-crystallins, and Tdrd7. Moreover, γA-crystallin- or Prox1-expressing lentoid bodies formed by 30 days in culture. In hES cells, Pax6 or Six3 lentiviral vectors also induced lens marker expression. mES cells that express lens markers reside close to but are distinct from the Pax6 or Six3 transduced cells, suggesting that the latter induce nearby undifferentiated ES cells to adopt a lens fate by non-cell autonomous mechanisms. In sum, we describe a novel mES cell GFP reporter line that is useful for monitoring induction of lens fate, and demonstrate that Pax6 or Six3 is sufficient to induce ES cells to adopt a lens fate, potentially via non-cell autonomous mechanisms. These findings should facilitate investigations of lens development

Effects of Heat Exposure on Body Water Assessed using Single-Frequency Bioelectrical Impedance Analysis and Bioimpedance Spectroscopy

International Journal of Exercise Science 10(7): 1085-1093, 2017. The purpose of this study was to determine if heat exposure alters the measures of total body water (TBW), extracellular water (ECW), and intracellular water (ICW) in both single-frequency bioelectrical impedance analysis (BIA) and bioimpedance spectroscopy (BIS). Additionally, we sought to determine if any differences exist between the BIA and BIS techniques before and after brief exposure to heat. Body water was evaluated for twenty men (age=24±4 years) in a thermoneutral environment (22°C) before (PRE) and immediately after (POST) 15 min of passive heating (35°C) in an environmental chamber. The mean difference and 95% limits of agreement at PRE demonstrated that BIS yielded significantly higher body water values than BIA (all p0.05; 0.2±1.5kg). Additionally, the ES of the mean differences at POST were trivial to small and the r-values were high (r≥0.96). When analyzing the changes in body water before and after heat exposure, POST values for BIS were significantly higher than PRE (all

Detection of Potential Transit Signals in the First Three Quarters of Kepler Mission Data

We present the results of a search for potential transit signals in the first three quarters of photometry data acquired by the Kepler Mission. The targets of the search include 151,722 stars which were observed over the full interval and an additional 19,132 stars which were observed for only 1 or 2 quarters. From this set of targets we find a total of 5,392 detections which meet the Kepler detection criteria: those criteria are periodicity of the signal, an acceptable signal-to-noise ratio, and a composition test which rejects spurious detections which contain non-physical combinations of events. The detected signals are dominated by events with relatively low signal-to-noise ratio and by events with relatively short periods. The distribution of estimated transit depths appears to peak in the range between 40 and 100 parts per million, with a few detections down to fewer than 10 parts per million. The detected signals are compared to a set of known transit events in the Kepler field of view which were derived by a different method using a longer data interval; the comparison shows that the current search correctly identified 88.1% of the known events. A tabulation of the detected transit signals, examples which illustrate the analysis and detection process, a discussion of future plans and open, potentially fruitful, areas of further research are included

College Binge Drinking Associated with Decreased Frontal Activation to Negative Emotional Distractors during Inhibitory Control

The transition to college is associated with an increase in heavy episodic alcohol use, or binge drinking, during a time when the prefrontal cortex and prefrontal-limbic circuitry continue to mature. Traits associated with this immaturity, including impulsivity in emotional contexts, may contribute to risky and heavy episodic alcohol consumption. The current study used blood oxygen level dependent (BOLD) multiband functional magnetic resonance imaging (fMRI) to assess brain activation during a task that required participants to ignore background images with positive, negative, or neutral emotional valence while performing an inhibitory control task (Go-NoGo). Subjects were 23 college freshmen (seven male, 18–20 years) who engaged in a range of drinking behavior (past 3 months’ binge episodes range = 0–19, mean = 4.6, total drinks consumed range = 0–104, mean = 32.0). Brain activation on inhibitory trials (NoGo) was contrasted between negative and neutral conditions and between positive and neutral conditions using non-parametric testing (5000 permutations) and cluster-based thresholding (z = 2.3), p ≤ 0.05 corrected. Results showed that a higher recent incidence of binge drinking was significantly associated with decreased activation of dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), and anterior cingulate cortex (ACC), brain regions strongly implicated in executive functioning, during negative relative to neutral inhibitory trials. No significant associations between binge drinking and brain activation were observed for positive relative to neutral images. While task performance was not significantly associated with binge drinking in this sample, subjects with heavier recent binge drinking showed decreased recruitment of executive control regions under negative versus neutral distractor conditions. These findings suggest that in young adults with heavier recent binge drinking, processing of negative emotional images interferes more with inhibitory control neurocircuitry than in young adults who do not binge drink often. This pattern of altered frontal lobe activation associated with binge drinking may serve as an early marker of risk for future self-regulation deficits that could lead to problematic alcohol use. These findings underscore the importance of understanding the impact of emotion on cognitive control and associated brain functioning in binge drinking behaviors among young adults

Linkage Disequilibrium in Wild Mice

Crosses between laboratory strains of mice provide a powerful way of detecting quantitative trait loci for complex traits related to human disease. Hundreds of these loci have been detected, but only a small number of the underlying causative genes have been identified. The main difficulty is the extensive linkage disequilibrium (LD) in intercross progeny and the slow process of fine-scale mapping by traditional methods. Recently, new approaches have been introduced, such as association studies with inbred lines and multigenerational crosses. These approaches are very useful for interval reduction, but generally do not provide single-gene resolution because of strong LD extending over one to several megabases. Here, we investigate the genetic structure of a natural population of mice in Arizona to determine its suitability for fine-scale LD mapping and association studies. There are three main findings: (1) Arizona mice have a high level of genetic variation, which includes a large fraction of the sequence variation present in classical strains of laboratory mice; (2) they show clear evidence of local inbreeding but appear to lack stable population structure across the study area; and (3) LD decays with distance at a rate similar to human populations, which is considerably more rapid than in laboratory populations of mice. Strong associations in Arizona mice are limited primarily to markers less than 100 kb apart, which provides the possibility of fine-scale association mapping at the level of one or a few genes. Although other considerations, such as sample size requirements and marker discovery, are serious issues in the implementation of association studies, the genetic variation and LD results indicate that wild mice could provide a useful tool for identifying genes that cause variation in complex traits

College Binge Drinking Associated with Decreased Frontal Activation to Negative Emotional Distractors during Inhibitory Control

The transition to college is associated with an increase in heavy episodic alcohol use, or binge drinking, during a time when the prefrontal cortex and prefrontal-limbic circuitry continue to mature. Traits associated with this immaturity, including impulsivity in emotional contexts, may contribute to risky and heavy episodic alcohol consumption. The current study used blood oxygen level dependent (BOLD) multiband functional magnetic resonance imaging (fMRI) to assess brain activation during a task that required participants to ignore background images with positive, negative, or neutral emotional valence while performing an inhibitory control task (Go-NoGo). Subjects were 23 college freshmen (seven male, 18–20 years) who engaged in a range of drinking behavior (past 3 months’ binge episodes range = 0–19, mean = 4.6, total drinks consumed range = 0–104, mean = 32.0). Brain activation on inhibitory trials (NoGo) was contrasted between negative and neutral conditions and between positive and neutral conditions using non-parametric testing (5000 permutations) and cluster-based thresholding (z = 2.3), p ≤ 0.05 corrected. Results showed that a higher recent incidence of binge drinking was significantly associated with decreased activation of dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), and anterior cingulate cortex (ACC), brain regions strongly implicated in executive functioning, during negative relative to neutral inhibitory trials. No significant associations between binge drinking and brain activation were observed for positive relative to neutral images. While task performance was not significantly associated with binge drinking in this sample, subjects with heavier recent binge drinking showed decreased recruitment of executive control regions under negative versus neutral distractor conditions. These findings suggest that in young adults with heavier recent binge drinking, processing of negative emotional images interferes more with inhibitory control neurocircuitry than in young adults who do not binge drink often. This pattern of altered frontal lobe activation associated with binge drinking may serve as an early marker of risk for future self-regulation deficits that could lead to problematic alcohol use. These findings underscore the importance of understanding the impact of emotion on cognitive control and associated brain functioning in binge drinking behaviors among young adults