Automatic annotation of bioinformatics workflows with biomedical ontologies

Legacy scientific workflows, and the services within them, often present scarce and unstructured (i.e. textual) descriptions. This makes it difficult to find, share and reuse them, thus dramatically reducing their value to the community. This paper presents an approach to annotating workflows and their subcomponents with ontology terms, in an attempt to describe these artifacts in a structured way. Despite a dearth of even textual descriptions, we automatically annotated 530 myExperiment bioinformatics-related workflows, including more than 2600 workflow-associated services, with relevant ontological terms. Quantitative evaluation of the Information Content of these terms suggests that, in cases where annotation was possible at all, the annotation quality was comparable to manually curated bioinformatics resources.Comment: 6th International Symposium on Leveraging Applications (ISoLA 2014 conference), 15 pages, 4 figure

Legal Resolution of Denial of Access to Medical Technology

The legal issues involved in technology application are inextricably interwoven with the medical issues. This Comment will first discuss the general principles of the scientific method and then contrast their application to pharmacologic therapy with their application to technologic treatments. Bone marrow transplantation will then be analyzed in depth, illustrating the medical issues that third-party payers consider in coverage decisions. Continuing with the model of bone marrow transplantation, this Comment will conclude with an analysis of legal solutions to the denial of access to medical technology

Legal Resolution of Denial of Access to Medical Technology

The legal issues involved in technology application are inextricably interwoven with the medical issues. This Comment will first discuss the general principles of the scientific method and then contrast their application to pharmacologic therapy with their application to technologic treatments. Bone marrow transplantation will then be analyzed in depth, illustrating the medical issues that third-party payers consider in coverage decisions. Continuing with the model of bone marrow transplantation, this Comment will conclude with an analysis of legal solutions to the denial of access to medical technology

Neural correlates of the behavioral-autonomic interaction response to potentially threatening stimuli

Subjective assessment of emotional valence is typically associated with both brain activity and autonomic arousal. Accurately assessing emotional salience is particularly important when perceiving threat. We sought to characterize the neural correlates of the interaction between behavioral and autonomic responses to potentially threatening visual and auditory stimuli. Twenty-five healthy male subjects underwent fMRI scanning whilst skin conductance responses (SCR) were recorded. One hundred and eighty pictures, sentences, and sounds were assessed as “harmless” or “threatening.” Individuals’ stimulus-locked, phasic SCRs and trial-by-trial behavioral assessments were entered as regressors into a flexible factorial design to establish their separate autonomic and behavioral neural correlates, and convolved to examine psycho-autonomic interaction (PAI) effects. Across all stimuli, “threatening,” compared with “harmless” behavioral assessments were associated with mainly frontal and precuneus activation with specific within-modality activations including bilateral parahippocampal gyri (pictures), bilateral anterior cingulate cortex (ACC) and frontal pole (sentences), and right Heschl’s gyrus and bilateral temporal gyri (sounds). Across stimulus modalities SCRs were associated with activation of parieto-occipito-thalamic regions, an activation pattern which was largely replicated within-modality. In contrast, PAI analyses revealed modality-specific activations including right fusiform/parahippocampal gyrus (pictures), right insula (sentences), and mid-cingulate gyrus (sounds). Phasic SCR activity was positively correlated with an individual’s propensity to assess stimuli as “threatening.” SCRs may modulate cognitive assessments on a “harmless–threatening” dimension, thereby modulating affective tone and hence behavior

Bioscientific data processing and modeling

Computer Systems, Imagery and Medi

Gaussian process manifold interpolation for probabilistic atrial activation maps and uncertain conduction velocity

In patients with atrial fibrillation, local activation time (LAT) maps are routinely used for characterizing patient pathophysiology. The gradient of LAT maps can be used to calculate conduction velocity (CV), which directly relates to material conductivity and may provide an important measure of atrial substrate properties. Including uncertainty in CV calculations would help with interpreting the reliability of these measurements. Here, we build upon a recent insight into reduced-rank Gaussian processes (GPs) to perform probabilistic interpolation of uncertain LAT directly on human atrial manifolds. Our Gaussian process manifold interpolation (GPMI) method accounts for the topology of the atrium, and allows for calculation of statistics for predicted CV. We demonstrate our method on two clinical cases, and perform validation against a simulated ground truth. CV uncertainty depends on data density, wave propagation direction and CV magnitude. GPMI is suitable for probabilistic interpolation of other uncertain quantities on non-Euclidean manifolds. This article is part of the theme issue ‘Uncertainty quantification in cardiac and cardiovascular modelling and simulation’

The state of tranquility: Subjective perception is shaped by contextual modulation of auditory connectivity

In this study, we investigated brain mechanisms for the generation of subjective experience from objective sensory inputs. Our experimental construct was subjective tranquility. Tranquility is a mental state more likely to occur in the presence of objective sensory inputs that arise from natural features in the environment. We used functional magnetic resonance imaging to examine the neural response to scenes that were visually distinct (beach images vs. freeway images) and experienced as tranquil (beach) or non-tranquil (freeway). Both sets of scenes had the same auditory component because waves breaking on a beach and vehicles moving on a freeway can produce similar auditory spectral and temporal characteristics, perceived as a constant roar. Compared with scenes experienced as non-tranquil, we found that subjectively tranquil scenes were associated with significantly greater effective connectivity between the auditory cortex and medial prefrontal cortex, a region implicated in the evaluation of mental states. Similarly enhanced connectivity was also observed between the auditory cortex and posterior cingulate gyrus, temporoparietal cortex and thalamus. These findings demonstrate that visual context can modulate connectivity of the auditory cortex with regions implicated in the generation of subjective states. Importantly, this effect arises under conditions of identical auditory input. Hence, the same sound may be associated with different percepts reflecting varying connectivity between the auditory cortex and other brain regions. This suggests that subjective experience is more closely linked to the connectivity state of the auditory cortex than to its basic sensory inputs

Sun exposure behaviour, seasonal vitamin D deficiency, and relationship to bone health in adolescents

YesContext: Vitamin D is essential for bone health in adolescence, where there is rapid bone mineral content accrual. As cutaneous sun-exposure provides vitamin D, there is no recommended oral intake for UK adolescents. Objective: Assess seasonal vitamin D status and its contributors in white Caucasian adolescents, and examine bone health in those found deficient. Design: Prospective cohort study. Setting: Six schools in Greater Manchester, UK. Participants: 131 adolescents, 12–15 years. Intervention(s): Seasonal assessment of circulating 25-hydroxyvitamin D (25OHD), personal sunexposure and dietary vitamin D. Adolescents deficient (25OHD <10 ng/mL/25 nmol/L) in ≥one season underwent dual-energy X-ray absorptiometry (lumbar spine, femoral neck), with bone mineral apparent density (BMAD) correction for size, and peripheral quantitative computed tomography (distal radius) for volumetric (v)BMD. Main Outcome Measure: Serum 25OHD; BMD. Results: Mean 25OHD was highest in September: 24.1 (SD 6.9) ng/mL and lowest in January: 15.5 (5.9) ng/mL. Over the year, 16% were deficient in ≥one season and 79% insufficient (25OHD <20 ng/mL/50 nmol/L) including 28% in September. Dietary vitamin D was low year-round while personal sun-exposure was seasonal and predominantly across the school week. Holidays accounted for 17% variation in peak 25OHD (p<0.001). Nineteen adolescents underwent bone assessment, which showed low femoral neck BMAD versus matched reference data (p=0.0002), 3 with Z≤ -2.0 distal radius trabecular vBMD. Conclusions: Sun-exposure levels failed to provide adequate vitamin D, ~one-quarter adolescents insufficient even at summer-peak. Seasonal vitamin D deficiency was prevalent and those affected had low BMD. Recommendations on vitamin D acquisition are indicated in this age-group.The Bupa Foundation (Grant number TBF-M10-017)

Genome-wide analysis of the H3K27me3 epigenome and transcriptome in brassica rapa

Background Genome-wide maps of histone modifications have been obtained for several plant species. However, most studies focus on model systems and do not enforce FAIR data management principles. Here we study the H3K27me3 epigenome and associated transcriptome of Brassica rapa, an important vegetable cultivated worldwide. Findings We performed H3K27me3 chromatin immunoprecipitation followed by high-throughput sequencing and transcriptomic analysis by 3′-end RNA sequencing from B. rapa leaves and inflorescences. To analyze these data we developed a Reproducible Epigenomic Analysis pipeline using Galaxy and Jupyter, packaged into Docker images to facilitate transparency and reuse. We found that H3K27me3 covers roughly one-third of all B. rapa protein-coding genes and its presence correlates with low transcript levels. The comparative analysis between leaves and inflorescences suggested that the expression of various floral regulatory genes during development depends on H3K27me3. To demonstrate the importance of H3K27me3 for B. rapa development, we characterized a mutant line deficient in the H3K27 methyltransferase activity. We found that braA.clf mutant plants presented pleiotropic alterations, e.g., curly leaves due to increased expression and reduced H3K27me3 levels at AGAMOUS-like loci. Conclusions We characterized the epigenetic mark H3K27me3 at genome-wide levels and provide genetic evidence for its relevance in B. rapa development. Our work reveals the epigenomic landscape of H3K27me3 in B. rapa and provides novel genomics datasets and bioinformatics analytical resources. We anticipate that this work will lead the way to further epigenomic studies in the complex genome of Brassica crops

Self-organized criticality in deterministic systems with disorder

Using the Bak-Sneppen model of biological evolution as our paradigm, we investigate in which cases noise can be substituted with a deterministic signal without destroying Self-Organized Criticality (SOC). If the deterministic signal is chaotic the universality class is preserved; some non-universal features, such as the threshold, depend on the time correlation of the signal. We also show that, if the signal introduced is periodic, SOC is preserved but in a different universality class, as long as the spectrum of frequencies is broad enough.Comment: RevTex, 8 pages, 8 figure