Discovering the location of gene duplications and multiple gene duplication episodes is a fundamental issue in evolutionary molecular biology. The problem introduced by Guigó et al. in 1996 is to map gene duplication events from a collection of rooted, binary gene family trees onto theirs corresponding rooted binary species tree in such a way that the total number of multiple gene duplication episodes is minimized. There are several models in the literature that specify how gene duplications from gene families can be interpreted as one duplication episode. However, in all duplication episode problems gene trees are rooted. This restriction limits the applicability, since unrooted gene family trees are frequently inferred by phylogenetic methods.
ResultsIn this article we show the first solution to the open problem of episode clustering where the input gene family trees are unrooted. In particular, by using theoretical properties of unrooted reconciliation, we show an efficient algorithm that reduces this problem into the episode clustering problems defined for rooted trees. We show theoretical properties of the reduction algorithm and evaluation of empirical datasets.
ConclusionsWe provided algorithms and tools that were successfully applied to several empirical datasets. In particular, our comparative study shows that we can improve known results on genomic duplication inference from real datasets.
相似文献Many adult congenital heart disease (ACHD) patients are at risk of sudden cardiac death (SCD). An implantable cardioverter-defibrillator (ICD) may prevent SCD, but the evidence for primary prevention indications is still unsatisfactory.
Study DesignPREVENTION-ACHD is a prospective study with which we aim to prospectively validate a new risk score model for primary prevention of SCD in ACHD patients, as well as the currently existing guideline recommendations. Patients are screened using a novel risk score to predict SCD as well as current ICD indications according to an international Consensus Statement. Patients are followed up for two years. The primary endpoint is the occurrence of SCD and sustained ventricular arrhythmias. The Study was registered at ClinicalTrials.gov (NCT03957824).
ConclusionPREVENTION-ACHD is the first prospective study on SCD in ACHD patients. In the light of a growing and aging population of patients with more severe congenital heart defects, more robust clinical evidence on primary prevention of SCD is urgently needed.
相似文献Genetic and environmental factors play a role in the development of COPD. The epigenome, and more specifically DNA methylation, is recognized as important link between these factors. We postulate that DNA methylation is one of the routes by which cigarette smoke influences the development of COPD. In this study, we aim to identify CpG-sites that are associated with cigarette smoke exposure and lung function levels in whole blood and validate these CpG-sites in lung tissue.
MethodsThe association between pack years and DNA methylation was studied genome-wide in 658 current smokers with >5 pack years using robust linear regression analysis. Using mediation analysis, we subsequently selected the CpG-sites that were also associated with lung function levels. Significant CpG-sites were validated in lung tissue with pyrosequencing and expression quantitative trait methylation (eQTM) analysis was performed to investigate the association between DNA methylation and gene expression.
Results15 CpG-sites were significantly associated with pack years and 10 of these were additionally associated with lung function levels. We validated 5 CpG-sites in lung tissue and found several associations between DNA methylation and gene expression.
ConclusionThis study is the first to validate a panel of CpG-sites that are associated with cigarette smoking and lung function levels in whole blood in the tissue of interest: lung tissue.
相似文献Biological networks describes the mechanisms which govern cellular functions. Temporal networks show how these networks evolve over time. Studying the temporal progression of network topologies is of utmost importance since it uncovers how a network evolves and how it resists to external stimuli and internal variations. Two temporal networks have co-evolving subnetworks if the evolving topologies of these subnetworks remain similar to each other as the network topology evolves over a period of time. In this paper, we consider the problem of identifying co-evolving subnetworks given a pair of temporal networks, which aim to capture the evolution of molecules and their interactions over time. Although this problem shares some characteristics of the well-known network alignment problems, it differs from existing network alignment formulations as it seeks a mapping of the two network topologies that is invariant to temporal evolution of the given networks. This is a computationally challenging problem as it requires capturing not only similar topologies between two networks but also their similar evolution patterns.
ResultsWe present an efficient algorithm, Tempo, for solving identifying co-evolving subnetworks with two given temporal networks. We formally prove the correctness of our method. We experimentally demonstrate that Tempo scales efficiently with the size of network as well as the number of time points, and generates statistically significant alignments—even when evolution rates of given networks are high. Our results on a human aging dataset demonstrate that Tempo identifies novel genes contributing to the progression of Alzheimer’s, Huntington’s and Type II diabetes, while existing methods fail to do so.
ConclusionsStudying temporal networks in general and human aging specifically using Tempo enables us to identify age related genes from non age related genes successfully. More importantly, Tempo takes the network alignment problem one huge step forward by moving beyond the classical static network models.
相似文献The long-term marginal electricity supply mixes of 40 countries were generated and integrated into version 3.4 of the ecoinvent consequential database. The total electricity production originating from these countries accounts for 77% of the current global electricity generation. The goal of this article is to provide an overview of the methodology used to calculate the marginal mixes and to evaluate the influence of key parameters and methodological choices on the results.
MethodsThe marginal mixes are based on public energy projections from national and international authorities and reflect the accumulated effect of changes in demand for electricity on the installation and operation of new-generation capacities. These newly generated marginal mixes are first examined in terms of their compositions and environmental impacts. They are then compared to several sets of alternative electricity supply mixes calculated using different methodological choices or data sources.
Results and discussionRenewable energy sources (RES) as well as natural gas power plants show the highest growth rates and usually dominate the marginal mixes. Nevertheless, important variations may exist between the marginal mixes of the different countries in terms of their technological compositions and environmental impacts. The examination of the modeling choices reveals substantial variations between the marginal mixes integrated into the ecoinvent consequential database version 3.4 and marginal mixes generated using alternative modeling options. These different modeling possibilities include changes in the methodology, temporal parameters, and the underlying energy scenarios. Furthermore, in most of the impact categories, average (i.e., attributional) mixes cause higher impact scores than marginal mixes due to higher shares of RES in marginal mixes.
ConclusionsAccurate and consistent data for electricity supply is integrated into a consequential database providing a strong basis for the development of consequential Life Cycle Assessments. The methodology adopted in this version of the database eliminates several shortcomings from the previous approach which led to unrealistic marginal mixes in several countries. The use of energy scenarios allows the evolution of the electricity system to be considered within the definition of the marginal mixes. The modeling choices behind the electricity marginal mix should be adjusted to the goal and scope of individual studies and their influence on the results evaluated.
相似文献Energy consumption of buildings is one of the major drivers of environmental impacts. Life cycle assessment (LCA) may support the assessment of burdens and benefits associated to eco-innovations aiming at reducing these environmental impacts. Energy efficiency policies however typically focus on the meso- or macro-scale, while interventions are typically taken at the micro-scale. This paper presents an approach that bridges this gap by using the results of energy simulations and LCA studies at the building level to estimate the effect of micro-scale eco-innovations on the macro-scale, i.e. the housing stock in Europe.
MethodsLCA and dynamic energy simulations are integrated to accurately assess the life cycle environmental burdens and benefits of eco-innovation measures at the building level. This allows quantitatively assessing the effectiveness of these measures to lower the energy use and environmental impact of buildings. The analysis at this micro-scale focuses on 24 representative residential buildings within the EU. For the upscaling to the EU housing stock, a hybrid approach is used. The results of the micro-scale analysis are upscaled to the EU housing stock scale by adopting the eco-innovation measures to (part of) the EU building stock (bottom–up approach) and extrapolating the relative impact reduction obtained for the reference buildings to the baseline stock model. The reference buildings in the baseline stock model have been developed by European Commission-Joint Research Centre based on a statistical analysis (top–down approach) of the European housing stock. The method is used to evaluate five scenarios covering various aspects: building components (building envelope insulation), technical installations (renewable energy), user behaviour (night setback of the setpoint temperature), and a combined scenario.
Results and discussionResults show that the proposed combination of bottom–up and top–down approaches allow accurately assessing the impact of eco-innovation measures at the macro-scale. The results indicate that a combination of policy measures is necessary to lower the environmental impacts of the building stock to a significative extent.
ConclusionsInterventions addressing energy efficiency at building level may lead to the need of a trade-off between resource efficiency and environmental impacts. LCA integrated with dynamic energy simulation may help unveiling the potential improvements and burdens associated to eco-innovations.
相似文献To infer gene regulatory networks (GRNs) from gene-expression data is still a fundamental and challenging problem in systems biology. Several existing algorithms formulate GRNs inference as a regression problem and obtain the network with an ensemble strategy. Recent studies on data driven dynamic network construction provide us a new perspective to solve the regression problem.
ResultsIn this study, we propose a data driven dynamic network construction method to infer gene regulatory network (D3GRN), which transforms the regulatory relationship of each target gene into functional decomposition problem and solves each sub problem by using the Algorithm for Revealing Network Interactions (ARNI). To remedy the limitation of ARNI in constructing networks solely from the unit level, a bootstrapping and area based scoring method is taken to infer the final network. On DREAM4 and DREAM5 benchmark datasets, D3GRN performs competitively with the state-of-the-art algorithms in terms of AUPR.
ConclusionsWe have proposed a novel data driven dynamic network construction method by combining ARNI with bootstrapping and area based scoring strategy. The proposed method performs well on the benchmark datasets, contributing as a competitive method to infer gene regulatory networks in a new perspective.
相似文献Haplotypes, the ordered lists of single nucleotide variations that distinguish chromosomal sequences from their homologous pairs, may reveal an individual’s susceptibility to hereditary and complex diseases and affect how our bodies respond to therapeutic drugs. Reconstructing haplotypes of an individual from short sequencing reads is an NP-hard problem that becomes even more challenging in the case of polyploids. While increasing lengths of sequencing reads and insert sizes helps improve accuracy of reconstruction, it also exacerbates computational complexity of the haplotype assembly task. This has motivated the pursuit of algorithmic frameworks capable of accurate yet efficient assembly of haplotypes from high-throughput sequencing data.
ResultsWe propose a novel graphical representation of sequencing reads and pose the haplotype assembly problem as an instance of community detection on a spatial random graph. To this end, we construct a graph where each read is a node with an unknown community label associating the read with the haplotype it samples. Haplotype reconstruction can then be thought of as a two-step procedure: first, one recovers the community labels on the nodes (i.e., the reads), and then uses the estimated labels to assemble the haplotypes. Based on this observation, we propose ComHapDet – a novel assembly algorithm for diploid and ployploid haplotypes which allows both bialleleic and multi-allelic variants.
ConclusionsPerformance of the proposed algorithm is benchmarked on simulated as well as experimental data obtained by sequencing Chromosome 5 of tetraploid biallelic Solanum-Tuberosum (Potato). The results demonstrate the efficacy of the proposed method and that it compares favorably with the existing techniques.
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