121 research outputs found

    Luonnollisiin audiovisuaalisiin Àrsykkeisiin liittyvÀn fMRI-aktivaation bayesilainen luokittelu harvoja ratkaisuja suosivia Laplace-prioreja kÀyttÀen

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    Bayesian linear binary classification models with sparsity promoting Laplace priors were applied to discriminate fMRI patterns related to natural auditory and audiovisual speech and music stimuli. The region of interest comprised the auditory cortex and some surrounding regions related to auditory processing. Truly sparse posterior mean solutions for the classifier weights were obtained by implementing an automatic relevance determination method using expectation propagation (ARDEP). In ARDEP, the Laplace prior was decomposed into a Gaussian scale mixture, and these scales were optimised by maximising their marginal posterior density. ARDEP was also compared to two other methods, which integrated approximately over the original Laplace prior: LAEP approximated the posterior as well by expectation propagation, whereas MCMC used a Markov chain Monte Carlo simulation method implemented by Gibbs sampling. The resulting brain maps were consistent with previous studies for simpler stimuli and suggested that the proposed model is also able to reveal additional information about activation patterns related to natural audiovisual stimuli. The predictive performance of the model was significantly above chance level for all approximate inference methods. Regardless of intensive pruning of features, ARDEP was able to describe all of the most discriminative brain regions obtained by LAEP and MCMC. However, ARDEP lost the more specific shape of the regions by representing them as one or more smaller spots, removing also some relevant features.Bayesilaisia lineaarisia binÀÀriluokittelumalleja ja harvoja ratkaisuja suosivia Laplace- prioreja sovellettiin erottelemaan luonnollisiin auditorisiin ja audiovisuaalisiin puhe- ja musiikkiÀrsykkeisiin liittyvÀÀ fMRI-aktivaatiota kuuloaivokuorella ja sitÀ ympÀröivillÀ auditoriseen prosessointiin liittyvillÀ alueilla. Absoluuttisen harvoja posteriorisia odotusarvoratkaisuja luokittimien painoille saatiin expectation propagation -algoritmin avulla toteutetulla automatic relevance determination -menetelmÀllÀ (ARDEP). ARDEP-menetelmÀssÀ hyödynnettiin Laplace-priorin gaussista skaalahajotelmaa, jonka skaalaparametrit optimoitiin maksimoimalla niiden marginaalinen posterioritiheys. MenetelmÀÀ verrattiin myös kahteen muuhun menetelmÀÀn, jotka integroivat approksimatiivisesti alkuperÀisen Laplace-priorin yli: LAEP approksimoi posteriorijakaumaa niin ikÀÀn expectation propagation -algoritmin avulla, kun taas MCMC kÀytti Gibbs -poiminnalla toteutettua Markovin ketju Monte Carlo -simulaatiomenetelmÀÀ. Tuloksena saadut aivokartat olivat linjassa aikaisempien, yksinkertaisemmilla ÀrsykkeillÀ saatujen tutkimustulosten kanssa, ja niiden perusteella bayesilaisten luokittelumallien avulla on mahdollista saada myös uudenlaista tietoa siitÀ, miten luonnollisia audiovisuaalisia ÀrsykkeitÀ koodataan aivoissa. Mallien ennustuskyky oli kaikilla approksimaatiomenetelmillÀ merkittÀvÀsti sattumanvaraista tasoa korkeampi. Piirteiden voimakkaasta karsinnasta huolimatta ARDEP pystyi kuvaamaan kaikki huomattavimmat LAEP:n ja MCMC:n erottelemat aivoalueet. ARDEP menetti kuitenkin alueiden tarkemman muodon esittÀmÀllÀ ne yhtenÀ tai useampana pienempÀnÀ alueena, poistaen myös osan merkittÀvistÀ piirteistÀ

    A multicomponent approach to using waste-derived biochar in biofiltration : A case study based on dissimilar types of waste

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    The environmental legislation and strict enforcement of environmental regulations are the tools effectively used for developing the market of materials for environmental protection technologies. Sustain ability criteria shift environmental engineering systems to more sustainable-material-based technologies. For carbon-based medium materials in biofiltration, this trend results in attempts to use biochar for biofiltration purposes. The paper presents the analysis of biochar properties based on the main criteria for biofiltration medium integrating the environmental quality properties of biochar, following the European Biochar Certificate guidelines. Three types of biochar produced from feedstock of highly popular and abundant types of waste are analysed. A multi component approach was applied to summarize the results. The lignocellulosic type of biochar was found to be more competitive for use as a biofiltration medium than the types of biochar with high ash or lignin content. (C) 2016 Elsevier Ltd. All rights reserved.Peer reviewe

    Brain-to-brain hyperclassification reveals action-specific motor mapping of observed actions in humans

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    Seeing an action may activate the corresponding action motor code in the observer. It remains unresolved whether seeing and performing an action activates similar action-specific motor codes in the observer and the actor. We used novel hyperclassification approach to reveal shared brain activation signatures of action execution and observation in interacting human subjects. In the first experiment, two "actors" performed four types of hand actions while their haemodynamic brain activations were measured with 3-T functional magnetic resonance imaging (fMRI). The actions were videotaped and shown to 15 "observers" during a second fMRI experiment. Eleven observers saw the videos of one actor, and the remaining four observers saw the videos of the other actor. In a control fMRI experiment, one of the actors performed actions with closed eyes, and five new observers viewed these actions. Bayesian canonical correlation analysis was applied to functionally realign observers' and actors' fMRI data. Hyperclassification of the seen actions was performed with Bayesian logistic regression trained on actors' data and tested with observers' data. Without the functional realignment, between-subjects accuracy was at chance level. With the realignment, the accuracy increased on average by 15 percentage points, exceeding both the chance level and the accuracy without functional realignment. The highest accuracies were observed in occipital, parietal and premotor cortices. Hyperclassification exceeded chance level also when the actor did not see her own actions. We conclude that the functional brain activation signatures underlying action execution and observation are partly shared, yet these activation signatures may be anatomically misaligned across individuals

    Đ€ĐŸŃ€ĐŒĐžŃ€ĐŸĐČĐ°ĐœĐžĐ” ŃĐŒĐŸŃ†ĐžĐŸĐœĐ°Đ»ŃŒĐœĐŸĐč ĐșŃƒĐ»ŃŒŃ‚ŃƒŃ€Ń‹ ĐșĐ°Đș ĐșĐŸĐŒĐżĐŸĐœĐ”ĐœŃ‚Đ° ĐžĐœĐœĐŸĐČĐ°Ń†ĐžĐŸĐœĐœĐŸĐč ĐșŃƒĐ»ŃŒŃ‚ŃƒŃ€Ń‹ ŃŃ‚ŃƒĐŽĐ”ĐœŃ‚ĐŸĐČ

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    Homozygosity has long been associated with rare, often devastating, Mendelian disorders1 and Darwin was one of the first to recognise that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity, ROH), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3,4. Here we use ROH to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts and find statistically significant associations between summed runs of homozygosity (SROH) and four complex traits: height, forced expiratory lung volume in 1 second (FEV1), general cognitive ability (g) and educational attainment (nominal p<1 × 10−300, 2.1 × 10−6, 2.5 × 10−10, 1.8 × 10−10). In each case increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing convincing evidence for the first time that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5,6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein (LDL) cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been

    Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

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    Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.Peer reviewe

    A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

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    Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways

    Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

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    Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

    Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

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    Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk

    Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

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    Funding GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska LĂ€karesĂ€llskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file 32: Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.Peer reviewedPublisher PD
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