Counting, generating and sampling tree alignments

Pairwise ordered tree alignment are combinatorial objects that appear in RNA secondary structure comparison. However, the usual representation of tree alignments as supertrees is ambiguous, i.e. two distinct supertrees may induce identical sets of matches between identical pairs of trees. This ambiguity is uninformative, and detrimental to any probabilistic analysis.In this work, we consider tree alignments up to equivalence. Our first result is a precise asymptotic enumeration of tree alignments, obtained from a context-free grammar by mean of basic analytic combinatorics. Our second result focuses on alignments between two given ordered trees $S$ and $T$. By refining our grammar to align specific trees, we obtain a decomposition scheme for the space of alignments, and use it to design an efficient dynamic programming algorithm for sampling alignments under the Gibbs-Boltzmann probability distribution. This generalizes existing tree alignment algorithms, and opens the door for a probabilistic analysis of the space of suboptimal RNA secondary structures alignments.Comment: ALCOB - 3rd International Conference on Algorithms for Computational Biology - 2016, Jun 2016, Trujillo, Spain. 201

Investigating the circulating sphingolipidome response to a single high-intensity interval training session within healthy females and males in their twenties (SphingoHIIT): Protocol for a randomised controlled trial.

Introduction: Growing scientific evidence indicates that sphingolipids predict cardiometabolic risk, independently of and beyond traditional biomarkers such as low-density lipoprotein cholesterol. To date, it remains largely unknown if and how exercise, a simple, low-cost, and patient-empowering modality to optimise cardiometabolic health, influences sphingolipid levels. The SphingoHIIT study aims to assess the response of circulating sphingolipid species to a single session of high-intensity interval training (HIIT). Methods: This single-centre randomised controlled trial (RCT) will last 11 days per participant and aim to include 32 young and healthy individuals aged 20-29 (50% females). Participants will be randomly allocated to the HIIT (n= 16) or control groups (physical rest, n= 16). Participants will self-sample fasted dried blood spots for three consecutive days before the intervention (HIIT versus rest) to determine baseline sphingolipid levels. Dried blood spots will also be collected at five time points (2, 15, 30, 60min, and 24h) following the intervention (HIIT versus rest). To minimise the dietary influence, participants will receive a standardised diet for four days, starting 24 hours before the first dried blood sampling. For females, interventions will be timed to fall within the early follicular phase to minimise the menstrual cycle's influence on sphingolipid levels. Finally, physical activity will be monitored for the whole study duration using a wrist accelerometer. Ethics and dissemination: The Ethics Committee of Northwest and Central Switzerland approved this protocol (ID 2022-00513). Findings will be disseminated in scientific journals and meetings. Trial Registration The trial was registered on www.clinicaltrials.gov (NCT05390866, https://clinicaltrials.gov/ct2/show/NCT05390866) on May 25, 2022

Effect of an eight-week high-intensity interval training programme on circulating sphingolipid levels in middle-aged adults at elevated cardiometabolic risk (SphingoFIT)-Protocol for a randomised controlled exercise trial.

Evidence indicates that sphingolipid accumulation drives complex molecular alterations promoting cardiometabolic diseases. Clinically, it was shown that sphingolipids predict cardiometabolic risk independently of and beyond traditional biomarkers such as low-density lipoprotein cholesterol. To date, little is known about therapeutic modalities to lower sphingolipid levels. Exercise, a powerful means to prevent and treat cardiometabolic diseases, is a promising modality to mitigate sphingolipid levels in a cost-effective, safe, and patient-empowering manner. This randomised controlled trial will explore whether and to what extent an 8-week fitness-enhancing training programme can lower serum sphingolipid levels of middle-aged adults at elevated cardiometabolic risk (n = 98, 50% females). The exercise intervention will consist of supervised high-intensity interval training (three sessions weekly), while the control group will receive physical activity counselling based on current guidelines. Blood will be sampled early in the morning in a fasted state before and after the 8-week programme. Participants will be provided with individualised, pre-packaged meals for the two days preceding blood sampling to minimise potential confounding. An 'omic-scale sphingolipid profiling, using high-coverage reversed-phase liquid chromatography coupled to tandem mass spectrometry, will be applied to capture the circulating sphingolipidome. Maximal cardiopulmonary exercise tests will be performed before and after the 8-week programme to assess patient fitness changes. Cholesterol, triglycerides, glycated haemoglobin, the homeostatic model assessment for insulin resistance, static retinal vessel analysis, flow-mediated dilatation, and strain analysis of the heart cavities will also be assessed pre- and post-intervention. This study shall inform whether and to what extent exercise can be used as an evidence-based treatment to lower circulating sphingolipid levels. The trial was registered on www.clinicaltrials.gov (NCT06024291) on August 28, 2023

Paroxysmal nocturnal hemoglobinuria (PNH): higher sensitivity and validity in diagnosis and serial monitoring by flow cytometric analysis of reticulocytes

Flow cytometric analysis of GPI-anchored proteins (GPI-AP) is the gold standard for diagnosis of paroxysmal nocturnal hemoglobinuria (PNH). Due to therapy options and the relevance of GPI-deficient clones for prognosis in aplastic anaemia detection of PNH is gaining importance. However, no generally accepted standard has been established. This study analysed the usefulness of a flow cytometric panel with CD58, CD59 on reticulocytes and erythrocytes, CD24/CD66b and CD16, FLAER on granulocytes and CD14, and CD48 on monocytes. Actual cut-off (mean + 2 SD) for GPI-deficient cells was established in healthy blood donors. We studied 1,296 flow cytometric results of 803 patients. Serial monitoring was analysed during a median follow-up of 1,039 days in 155 patients. Of all, 22% and 48% of 155 follow-up patients. showed significant GPI-AP-deficiency at time of initial analyses. During follow-up in 9%, a new PNH diagnosis, and in 28%, a significant change of size or lineage involvement was demonstrated. Highly significant correlations for GPI-AP deficiency were found within one cell lineage (r2 = 0.61–0.95, p < 0.0001) and between the different cell lineages (r2 = 0.49–0.88, p < 0.0001). Especially for detection of small GPI-deficient populations, reticulocytes and monocytes proved to be sensitive diagnostic tools. Our data showed superiority of reticulocyte analyses compared with erythrocyte analyses due to transfusion and hemolysis independency especially in cases with small GPI-deficient populations. In conclusion, a screening panel of at least two different GPI-AP markers on granulocytes, erythrocytes, and reticulocytes provides a simple and rapid method to detect even small GPI-deficient populations. Among the markers in our panel, CD58 and CD59 on reticulocytes, CD24/66b, and eventually FLAER on granulocytes as well as CD14 on monocytes were most effective for flow cytometric diagnosis of GPI deficiency

Effects of using coding potential, sequence conservation and mRNA structure conservation for predicting pyrroly-sine containing genes

BACKGROUND: Pyrrolysine (the 22nd amino acid) is in certain organisms and under certain circumstances encoded by the amber stop codon, UAG. The circumstances driving pyrrolysine translation are not well understood. The involvement of a predicted mRNA structure in the region downstream UAG has been suggested, but the structure does not seem to be present in all pyrrolysine incorporating genes. RESULTS: We propose a strategy to predict pyrrolysine encoding genes in genomes of archaea and bacteria. We cluster open reading frames interrupted by the amber codon based on sequence similarity. We rank these clusters according to several features that may influence pyrrolysine translation. The ranking effects of different features are assessed and we propose a weighted combination of these features which best explains the currently known pyrrolysine incorporating genes. We devote special attention to the effect of structural conservation and provide further substantiation to support that structural conservation may be influential – but is not a necessary factor. Finally, from the weighted ranking, we identify a number of potentially pyrrolysine incorporating genes. CONCLUSIONS: We propose a method for prediction of pyrrolysine incorporating genes in genomes of bacteria and archaea leading to insights about the factors driving pyrrolysine translation and identification of new gene candidates. The method predicts known conserved genes with high recall and predicts several other promising candidates for experimental verification. The method is implemented as a computational pipeline which is available on request

Behavioural determinants of physical activity across the life course: a "Determinants of Diet and Physical Activity" (DEDIPAC) umbrella literature review

Background Low levels of physical activity (PA) are a global concern and increasing PA engagement is becoming a priority in current public health policies. Despite the large number of studies and reviews available, the evidence regarding the behavioral determinants of PA is still inconclusive. Thus, the aim of this umbrella systematic literature review (SLR) was to summarize the evidence on the behavioral determinants of PA across the life course. Methods A systematic online search was conducted on MEDLINE, ISI Web of Science, Scopus, and SPORTDiscus databases. The search was limited to studies published in English from January, 2004 to April, 2016. SLRs and meta-analyses (MAs) of observational studies that investigated the behavioral determinants of PA were considered eligible. The extracted data were assessed based on the importance of the determinants, the strength of evidence, and the methodological quality. The full protocol is available from PROSPERO (PROSPERO 2014:CRD42015010616). Results Seventeen reviews on 35 behavioral determinants of PA were eligible for this umbrella SLR. Regardless of age, the most investigated determinants were those related with ‘screen use’ and ‘smoking’. For youth, probable positive evidence emerged for ‘previous PA’ and ‘independent mobility and active transport’ among children and adolescents. For the adult population, ‘transition to university’ and ‘pregnancy/having a child’ showed probable negative associations. Conclusions Although the majority of the evidence was limited and most of the determinants were not associated with PA, this umbrella SLR provided a comprehensive overview of the associations between behavioral determinants and PA. Youth should be physically active in the early years and increase active transportation to/from school, independent mobility, and ‘free-range activities’ without adult supervision, whilst adult PA behaviors are mostly influenced by the life events. Finally, more research is needed that incorporates prospective study designs, standardized definitions of PA, objective measurement methods of PA assessment, and the use of interactionist and mediational approaches for the evaluation of different behavioral determinants influencing PA behaviors

ViennaRNA Package 2.0

<p>Abstract</p> <p>Background</p> <p>Secondary structure forms an important intermediate level of description of nucleic acids that encapsulates the dominating part of the folding energy, is often well conserved in evolution, and is routinely used as a basis to explain experimental findings. Based on carefully measured thermodynamic parameters, exact dynamic programming algorithms can be used to compute ground states, base pairing probabilities, as well as thermodynamic properties.</p> <p>Results</p> <p>The <monospace>ViennaRNA</monospace> Package has been a widely used compilation of RNA secondary structure related computer programs for nearly two decades. Major changes in the structure of the standard energy model, the <it>Turner 2004 </it>parameters, the pervasive use of multi-core CPUs, and an increasing number of algorithmic variants prompted a major technical overhaul of both the underlying <monospace>RNAlib</monospace> and the interactive user programs. New features include an expanded repertoire of tools to assess RNA-RNA interactions and restricted ensembles of structures, additional output information such as <it>centroid </it>structures and <it>maximum expected accuracy </it>structures derived from base pairing probabilities, or <it>z</it>-<it>scores </it>for locally stable secondary structures, and support for input in <monospace>fasta</monospace> format. Updates were implemented without compromising the computational efficiency of the core algorithms and ensuring compatibility with earlier versions.</p> <p>Conclusions</p> <p>The <monospace>ViennaRNA Package 2.0</monospace>, supporting concurrent computations <monospace>via OpenMP</monospace>, can be downloaded from <url>http://www.tbi.univie.ac.at/RNA</url>.</p