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2.
Braz J Microbiol ; 51(3): 1109-1115, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32809115

RESUMO

COVID-19 has killed more than 500,000 people worldwide and more than 60,000 in Brazil. Since there are no specific drugs or vaccines, the available tools against COVID-19 are preventive, such as the use of personal protective equipment, social distancing, lockdowns, and mass testing. Such measures are hindered in Brazil due to a restrict budget, low educational level of the population, and misleading attitudes from the federal authorities. Predictions for COVID-19 are of pivotal importance to subsidize and mobilize health authorities' efforts in applying the necessary preventive strategies. The Weibull distribution was used to model the forecast prediction of COVID-19, in four scenarios, based on the curve of daily new deaths as a function of time. The date in which the number of daily new deaths will fall below the rate of 3 deaths per million - the average level in which some countries start to relax the stay-at-home measures - was estimated. If the daily new deaths curve was bending today (i.e., about 1250 deaths per day), the predicted date would be on July 5. Forecast predictions allowed the estimation of overall death toll at the end of the outbreak. Our results suggest that each additional day that lasts to bend the daily new deaths curve may correspond to additional 1685 deaths at the end of COVID-19 outbreak in Brazil (R2 = 0.9890). Predictions of the outbreak can be used to guide Brazilian health authorities in the decision-making to properly fight COVID-19 pandemic.


Assuntos
Infecções por Coronavirus/epidemiologia , Previsões/métodos , Pneumonia Viral/epidemiologia , Algoritmos , Brasil/epidemiologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/prevenção & controle , Detergentes/provisão & distribução , Educação/estatística & dados numéricos , Humanos , Análise dos Mínimos Quadrados , Dinâmica não Linear , Pandemias/prevenção & controle , Pneumonia Viral/mortalidade , Pneumonia Viral/prevenção & controle , Política , Densidade Demográfica , Pobreza , Fatores Socioeconômicos , Estatística como Assunto , Fatores de Tempo , Abastecimento de Água/normas
3.
PLoS One ; 15(7): e0236079, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32735597

RESUMO

In this preregistered study, we investigated whether the statistical power of a study is higher when researchers are asked to make a formal power analysis before collecting data. We compared the sample size descriptions from two sources: (i) a sample of pre-registrations created according to the guidelines for the Center for Open Science Preregistration Challenge (PCRs) and a sample of institutional review board (IRB) proposals from Tilburg School of Behavior and Social Sciences, which both include a recommendation to do a formal power analysis, and (ii) a sample of pre-registrations created according to the guidelines for Open Science Framework Standard Pre-Data Collection Registrations (SPRs) in which no guidance on sample size planning is given. We found that PCRs and IRBs (72%) more often included sample size decisions based on power analyses than the SPRs (45%). However, this did not result in larger planned sample sizes. The determined sample size of the PCRs and IRB proposals (Md = 90.50) was not higher than the determined sample size of the SPRs (Md = 126.00; W = 3389.5, p = 0.936). Typically, power analyses in the registrations were conducted with G*power, assuming a medium effect size, α = .05 and a power of .80. Only 20% of the power analyses contained enough information to fully reproduce the results and only 62% of these power analyses pertained to the main hypothesis test in the pre-registration. Therefore, we see ample room for improvements in the quality of the registrations and we offer several recommendations to do so.


Assuntos
Comitês de Ética em Pesquisa , Tamanho da Amostra , Estatística como Assunto/métodos
4.
PLoS One ; 15(8): e0237859, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32833986

RESUMO

OBJECTIVES: The aim of our study is to examine the association between knowledge about the World War II (WWII)-related traumatic experiences of their ancestors and subjective well-being (SWB) of young adults, i.e., descendants of Polish survivors of WWII. Specifically, we focus on the life satisfaction and the mental, physical, and psychosocial well-being of our participants in relation to their knowledge about WWII trauma in their family histories. METHOD: The sample comprised 500 Polish young adults recruited from a nonclinical general population. Participants first filled out a questionnaire assessing their knowledge about traumatic events that their ancestors could have experienced during WWII (see grandparents/mothers, great-grandparents/mothers). After that, subjects were given inventories to assess their SWB, i.e., the Satisfaction with Life Scale (SWLS) and the General Health Questionnaire (GHQ-28). RESULTS: Latent profile analysis was applied to extract profiles of participants differing with regard to the scope of knowledge about WWII-related traumatic experiences among ancestors. Specifically, six profiles were observed, and a general lack of knowledge about this kind of trauma in the family was characteristic of the sample. We also found differences in SWB across profiles of participants, with worse SWB in the profiles with the highest lack of knowledge about WWII-related traumatic experiences in the family. CONCLUSION: Our study adds to the literature on intergenerational trauma by applying a person-centred perspective, a methodological approach almost invisible in research on that topic. In addition, our findings can serve as a stimulus for more comprehensive debate on WWII trauma in Polish society.


Assuntos
Família , Conhecimento , Transtornos de Estresse Pós-Traumáticos/psicologia , II Guerra Mundial , Adolescente , Adulto , Feminino , Humanos , Masculino , Negociação , Satisfação Pessoal , Estatística como Assunto , Inquéritos e Questionários , Adulto Jovem
5.
BMC Bioinformatics ; 21(1): 345, 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32778056

RESUMO

BACKGROUND: Comparing the composition of microbial communities among groups of interest (e.g., patients vs healthy individuals) is a central aspect in microbiome research. It typically involves sequencing, data processing, statistical analysis and graphical display. Such an analysis is normally obtained by using a set of different applications that require specific expertise for installation, data processing and in some cases, programming skills. RESULTS: Here, we present SHAMAN, an interactive web application we developed in order to facilitate the use of (i) a bioinformatic workflow for metataxonomic analysis, (ii) a reliable statistical modelling and (iii) to provide the largest panel of interactive visualizations among the applications that are currently available. SHAMAN is specifically designed for non-expert users. A strong benefit is to use an integrated version of the different analytic steps underlying a proper metagenomic analysis. The application is freely accessible at http://shaman.pasteur.fr/ , and may also work as a standalone application with a Docker container (aghozlane/shaman), conda and R. The source code is written in R and is available at https://github.com/aghozlane/shaman . Using two different datasets (a mock community sequencing and a published 16S rRNA metagenomic data), we illustrate the strengths of SHAMAN in quickly performing a complete metataxonomic analysis. CONCLUSIONS: With SHAMAN, we aim at providing the scientific community with a platform that simplifies reproducible quantitative analysis of metagenomic data.


Assuntos
Classificação , Internet , Metagenômica/métodos , Software , Estatística como Assunto , Interface Usuário-Computador , Líquidos Corporais/microbiologia , Pré-Escolar , Fezes/microbiologia , Humanos , Metagenoma , Microbiota , RNA Ribossômico 16S/genética , Fluxo de Trabalho
6.
PLoS One ; 15(8): e0237818, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32853245

RESUMO

Functional and enduring mammary structure is pivotal for producer profitability, and animal health and welfare in beef production. Genetic evaluations for teat and udder score in Canadian Angus cattle have previously been developed. The aim of this study was to identify genomic regions associated with teat and udder structure in Canadian Angus cows thereby enhancing knowledge of the biological architecture of these traits. Thus, we performed a weighted single-step genome wide association study (WssGWAS) to identify candidate genes for teat and udder score in 1,582 Canadian Angus cows typed with the GeneSeek® Genomic Profiler Bovine 130K SNP array. Genomically enhanced estimated breeding values (GEBVs) were converted to SNP marker effects using unequal variances for markers to calculate weights for each SNP over three iterations. At the genome wide level, we detected windows of 20 consecutive SNPs that explained more than 0.5% of the variance observed in these traits. A total of 35 and 28 windows were identified for teat and udder score, respectively, with two SNP windows in common for both traits. Using Ensembl, the SNP windows were used to search for candidate genes and quantitative trait loci (QTL). A total of 94 and 71 characterized genes were identified in the regions for teat and udder score, respectively. Of these, 7 genes were common for both traits. Gene network and enrichment analysis, using Ingenuity Pathway Analysis (IPA), signified key pathways unique to each trait. Genes of interest were associated with immune response and wound healing, adipose tissue development and morphology, and epithelial and vascular development and morphology. Genetic architecture from this GWAS confirms that teat and udder score are distinct, polygenic traits involving varying and complex biological pathways, and that genetic selection for improved teat and udder score is possible.


Assuntos
Bovinos/anatomia & histologia , Bovinos/genética , Estudo de Associação Genômica Ampla , Glândulas Mamárias Animais/anatomia & histologia , Animais , Feminino , Redes Reguladoras de Genes , Anotação de Sequência Molecular , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Software , Estatística como Assunto
7.
J Chromatogr A ; 1625: 461261, 2020 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-32709318

RESUMO

The high cost of protein A resins drives the biopharmaceutical industry to maximize its lifetime, which is limited by several processes, usually referred to as resin aging. In this work, two model based strategies are presented, aiming to control and improve the resin lifetime. The first approach, purely statistical, enables qualitative monitoring of the column state and prediction of column performance indicators (e.g. yield, purity and dynamic binding capacity) from chromatographic on-line data (e.g. UV signal). The second one, referred to as hybrid modeling, is based on a lumped kinetic model, which includes two aging parameters fitted on several resin cycling experimental campaigns with varying cleaning procedures (CP). The first aging parameter accounts for binding capacity deterioration (caused by ligand degradation, leaching, and pore occlusion), while the second accounts for a decreased mass transfer rate (mainly caused by fouling). The hybrid model provides important insights into the prevailing aging mechanism as a function of the different CPs. In addition, it can be applied to model based CP optimization and yield forecasting with the capability of state estimation corrections based on on-line process information. Both approaches show promising results, which could help to significantly extend the resin lifetime. This comes along with increased understanding, reduced experimental effort, decreased cost of goods, and improved process robustness.


Assuntos
Cromatografia/métodos , Modelos Teóricos , Resinas Vegetais/química , Proteína Estafilocócica A/química , Algoritmos , Cinética , Análise dos Mínimos Quadrados , Ligantes , Análise de Componente Principal , Estatística como Assunto
8.
BMC Bioinformatics ; 21(Suppl 12): 306, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32703258

RESUMO

BACKGROUND: Graph-based representation of genome assemblies has been recently used in different contexts - from improved reconstruction of plasmid sequences and refined analysis of metagenomic data to read error correction and reference-free haplotype reconstruction. While many of these applications heavily utilize the alignment of long nucleotide sequences to assembly graphs, first general-purpose software tools for finding such alignments have been released only recently and their deficiencies and limitations are yet to be discovered. Moreover, existing tools can not perform alignment of amino acid sequences, which could prove useful in various contexts - in particular the analysis of metagenomic sequencing data. RESULTS: In this work we present a novel SPAligner (Saint-Petersburg Aligner) tool for aligning long diverged nucleotide and amino acid sequences to assembly graphs. We demonstrate that SPAligner is an efficient solution for mapping third generation sequencing reads onto assembly graphs of various complexity and also show how it can facilitate the identification of known genes in complex metagenomic datasets. CONCLUSIONS: Our work will facilitate accelerating the development of graph-based approaches in solving sequence to genome assembly alignment problem. SPAligner is implemented as a part of SPAdes tools library and is available on Github.


Assuntos
Algoritmos , Variação Genética , Alinhamento de Sequência , Sequência de Bases , Haplótipos/genética , Humanos , Software , Estatística como Assunto , beta-Lactamases/química
9.
PLoS One ; 15(7): e0236067, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32678828

RESUMO

INTRODUCTION: In many practical situations, we are interested in the effect of covariates on correlated multiple responses. In this paper, we focus on estimation and variable selection in multi-response multiple regression models. Correlation among the response variables must be modeled for valid inference. METHOD: We used an extension of the generalized estimating equation (GEE) methodology to simultaneously analyze binary, count, and continuous outcomes with nonlinear functions. Variable selection plays an important role in modeling correlated responses because of the large number of model parameters that must be estimated. We propose a penalized-likelihood approach based on the extended GEEs for simultaneous parameter estimation and variable selection. RESULTS AND CONCLUSIONS: We conducted a series of Monte Carlo simulations to investigate the performance of our method, considering different sample sizes and numbers of response variables. The results showed that our method works well compared to treating the responses as uncorrelated. We recommend using an unstructured correlation model with the Bayesian information criterion (BIC) to select the tuning parameters. We demonstrated our method using data from a concrete slump test.


Assuntos
Estatística como Assunto/métodos , Análise Multivariada , Análise de Regressão
10.
BMC Bioinformatics ; 21(1): 335, 2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32727350

RESUMO

BACKGROUND: The efficient and robust statistical analysis of the shape of plant organs of different cultivars is an important investigation issue in plant breeding and enables a robust cultivar description within the breeding progress. Laserscanning is a highly accurate and high resolution technique to acquire the 3D shape of plant surfaces. The computation of a shape based principal component analysis (PCA) built on concepts from continuum mechanics has proven to be an effective tool for a qualitative and quantitative shape examination. RESULTS: The shape based PCA was used for a statistical analysis of 140 sugar beet roots of different cultivars. The calculation of the mean sugar beet root shape and the description of the main variations was possible. Furthermore, unknown and individual tap roots could be attributed to their cultivar by means of a robust classification tool based on the PCA results. CONCLUSION: The method demonstrates that it is possible to identify principal modes of root shape variations automatically and to quantify associated variances out of laserscanned 3D sugar beet tap root models. The introduced approach is not limited to the 3D shape description by laser scanning. A transfer to 3D MRI or radar data is also conceivable.


Assuntos
Beta vulgaris/anatomia & histologia , Lasers , Raízes de Plantas/anatomia & histologia , Estatística como Assunto , Análise de Componente Principal
11.
PLoS One ; 15(7): e0236299, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32692765

RESUMO

This study investigates the environmental and economic impacts of the Kyoto Protocol on Annex I parties through an impact assessment by combining the propensity score matching and the difference-in-difference methods. We establish a country-level panel data set including CO2 emissions, gross domestic product (GDP), and other socioeconomic data for 1997-2008 and 2005-2008. Based on the impact evaluation, we conduct the simulation predicting the impacts of the Protocol to capture the differences of marginal damage cost of carbon emissions between the actual and counterfactual situations. The results suggest that participating as an Annex I party has a significant positive impact on CO2 emission reductions, but a negative impact on the GDP of the participants in the long run. The predicted marginal benefit of the Protocol based on the marginal damage cost of carbon emissions shows that the marginal benefit of emission reductions mitigates a limited portion of the GDP loss. Future global climate change frameworks should focus on balancing the impact on economic and environmental performance in order to ensure sustainable development, especially for developing countries that have low capacity to mitigate emissions.


Assuntos
Desenvolvimento Econômico , Meio Ambiente , Poluição do Ar/análise , Dióxido de Carbono/análise , Produto Interno Bruto , Estatística como Assunto
12.
PLoS One ; 15(7): e0236258, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32701955

RESUMO

Parkinson's disease (PD) is a neurodegenerative disease inducing dystrophy of the motor system. Automatic movement analysis systems have potential in improving patient care by enabling personalized and more accurate adjust of treatment. These systems utilize machine learning to classify the movement properties based on the features derived from the signals. Smartphones can provide an inexpensive measurement platform with their built-in sensors for movement assessment. This study compared three feature selection and nine classification methods for identifying PD patients from control subjects based on accelerometer and gyroscope signals measured with a smartphone during a 20-step walking test. Minimum Redundancy Maximum Relevance (mRMR) and sequential feature selection with both forward (SFS) and backward (SBS) propagation directions were used in this study. The number of selected features was narrowed down from 201 to 4-15 features by applying SFS and mRMR methods. From the methods compared in this study, the highest accuracy for individual steps was achieved with SFS (7 features) and Naive Bayes classifier (accuracy 75.3%), and the second highest accuracy with SFS (4 features) and k Nearest neighbours (accuracy 75.1%). Leave-one-subject-out cross-validation was used in the analysis. For the overall classification of each subject, which was based on the majority vote of the classified steps, k Nearest Neighbors provided the most accurate result with an accuracy of 84.5% and an error rate of 15.5%. This study shows the differences in feature selection methods and classifiers and provides generalizations for optimizing methodologies for smartphone-based monitoring of PD patients. The results are promising for further developing the analysis system for longer measurements carried out in free-living conditions.


Assuntos
Teste de Esforço , Aprendizado de Máquina , Doença de Parkinson/diagnóstico , Doença de Parkinson/fisiopatologia , Smartphone , Caminhada/fisiologia , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Processamento de Sinais Assistido por Computador , Estatística como Assunto , Máquina de Vetores de Suporte
13.
PLoS One ; 15(7): e0236479, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32716950

RESUMO

BACKGROUND: Many studies have identified an inequitable distribution of exposure to PM2.5 (particulate matter less than 2.5 microns) by race. We investigated the association of PM2.5 and cardiovascular mortality considering both the decedents' race and neighborhood racial composition as potential modifiers. METHODS: We obtained geocoded cardiovascular mortality records of all black and white decedents from urban block-groups in Massachusetts between 2001 and 2011 (n = 130,863). We examined the association between PM2.5 and cardiovascular mortality, and assessed effect modification by three types of racial modifiers: decedents' race, census block-group percent black and white, and two novel measures of racial segregation. The Racial Residential Segregation (RRS) quantifies the concentration of non-Hispanic blacks and whites in each block-group. The Index of Racial Dissimilarity measures dissimilarity in non-Hispanic black and white racial distribution between the smaller census block-group and larger tract. RESULTS: We found a 2.35%(95%CI: 0.92%;3.79%) increase in mortality for each 10µg/m3 increase in two-day average exposure to PM2.5. The effect was modified by the block-group racial composition, with higher risks in block-groups with the highest percentage of black residents (interaction p-value = 0.04), and in block-groups with the lowest RRS (i.e. higher black to white resident ratio, interaction p-value = 0.072). Racial dissimilarity did not modify the associations. CONCLUSION: Current levels of PM2.5 are associated with increased cardiovascular deaths in Massachusetts, with different risks between areas with different racial composition and segregation. This suggests that pollution reductions in neighborhoods with the highest percentage of non-Hispanic blacks would be most beneficial in reducing cardiovascular mortality and disparities.


Assuntos
Doenças Cardiovasculares/etnologia , Doenças Cardiovasculares/mortalidade , Grupos de Populações Continentais , Tamanho da Partícula , Material Particulado/efeitos adversos , Material Particulado/química , Segregação Social , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Fatores de Risco , Estatística como Assunto , População Urbana
14.
PLoS One ; 15(7): e0236486, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730296

RESUMO

We collect data on time preferences of a representative sample of the Hungarian adult population in a non-incentivized way and investigate how patience and present bias associate with important life outcomes in five domains: i) educational attainment, ii) unemployment, iii) income and wealth, iv) financial decisions and difficulties, and v) health. Based on the literature, we formulate the broad hypotheses that patience relates positively, while present bias associates negatively with positive outcomes in the domains under study. With the exception of unemployment, we document a consistent and often significant positive relationship between patience and the corresponding domain, with the strongest associations in educational attainment, wealth and financial decisions. We find that present bias associates significantly with saving decisions and financial difficulties.


Assuntos
Inquéritos e Questionários , Viés , Comércio , Tomada de Decisões , Escolaridade , Saúde , Humanos , Renda , Probabilidade , Análise de Regressão , Estatística como Assunto , Fatores de Tempo , Desemprego
15.
PLoS One ; 15(7): e0236356, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730351

RESUMO

BACKGROUND: Topical cocaine is favoured by many surgeons for sinonasal surgery due to its superior vasoconstrictive and anesthetic properties. However, historical reports suggesting cocaine is associated with an increased risk of cardiac events have led many surgeons to turn to alternative topical medications. The objective of this study was to determine whether cocaine use during sinonasal surgery is associated with an increased risk of perioperative cardiac events and death. METHODS: We conducted a population-based analysis of patients undergoing sinonasal surgery from 2009-2016 using linked administrative health care data sets in Ontario, Canada. We compared patients treated at institutions that primarily use topical cocaine (exposed group) to those treated at institutions that do not use cocaine (unexposed group). Our primary outcome was a composite of major cardiac events or all-cause mortality within 48 hours of surgery. Due to low event rates, the outcome was compared using a Fisher's exact test. RESULTS: Of 10,549 patients who were included in the study, 27.4% were treated at an institution that uses topical cocaine. The rate of the composite of perioperative major cardiac event or all-cause mortality within 48 hours of surgery in the exposed and unexposed groups was, ≤0.2% and 0 (p-value>0.05), respectively. CONCLUSIONS: In this large real-world cohort of patients undergoing sinonasal surgery, there does not appear to be any significant increased risk of morbidity or mortality associated with cocaine use. These findings have important implications for surgeons performing this procedure.


Assuntos
Cocaína/uso terapêutico , Morbidade , Seios Paranasais/cirurgia , Assistência Perioperatória , Administração Tópica , Cocaína/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estatística como Assunto , Resultado do Tratamento
16.
BMC Evol Biol ; 20(1): 78, 2020 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600249

RESUMO

BACKGROUND: The molecular clock is an important genetic tool for estimating evolutionary timescales. However, the detection of a time-dependent effect on substitution rate estimates complicates its application. It has been suggested that demographic processes could be the main cause of this confounding effect. In the present study, I propose a new algorithm for estimating the coalescent age of phylogenetically related sequences, taking into account the observed time-dependent effect on the molecular rate detected by others. RESULTS: By applying this method to real human mitochondrial DNA trees with shallow and deep topologies, I obtained significantly older molecular ages for the main events of human evolution than were previously estimated. These ages are in close agreement with the most recent archaeological and paleontological records favoring the emergence of early anatomically modern humans in Africa 315 ± 34 thousand years ago (kya) and the presence of recent modern humans outside of Africa as early as 174 ± 48 thousand years ago. Furthermore, during the implementation process, I demonstrated that in a population with fluctuating sizes, the probability of fixation of a new neutral mutant depends on the effective population size, which is in better accordance with the fact that under the neutral theory of molecular evolution, the fate of a molecular mutation is mainly determined by random drift. CONCLUSIONS: I suggest that the demographic history of populations has a more decisive effect than purifying selection and/or mutational saturation on the time-dependent effect observed for the substitution rate, and I propose a new method that corrects for this effect.


Assuntos
DNA Mitocondrial/genética , Evolução Biológica , Evolução Molecular , Humanos , Modelos Genéticos , Mutação/genética , Filogenia , Estatística como Assunto , Fatores de Tempo
17.
PLoS One ; 15(7): e0235596, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32716924

RESUMO

We propose a method to simplify textual Twitter data into understandable networks of terms that can signify important events and their possible changes over time. The method allows for common characteristics of the networks across time periods and each period can comprise multiple unknown sub-networks. The networks are described by Gaussian graphical models and their parameter values are estimated through a Bayesian approach with a fused lasso-type prior on the precision matrices of the underlying mixtures of the sub-models. A flexible data allocation scheme is at the heart of an MCMC algorithm to recover mean and covariance parameters of the mixture components. Several implementations of the outlined estimation procedure are studied and compared based on simulated data. The procedure with the highest predictive power is used for mining tweets regarding the 2009 Iranian presidential election.


Assuntos
Gráficos por Computador , Mídias Sociais/estatística & dados numéricos , Estatística como Assunto/métodos , Teorema de Bayes , Modelos Estatísticos
20.
Nat Commun ; 11(1): 2821, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32499584

RESUMO

Altered metabolism is associated with many human diseases. Human genome-scale metabolic models (GEMs) were reconstructed within systems biology to study the biochemistry occurring in human cells. However, the complexity of these networks hinders a consistent and concise physiological representation. We present here redHUMAN, a workflow for reconstructing reduced models that focus on parts of the metabolism relevant to a specific physiology using the recently established methods redGEM and lumpGEM. The reductions include the thermodynamic properties of compounds and reactions guaranteeing the consistency of predictions with the bioenergetics of the cell. We introduce a method (redGEMX) to incorporate the pathways used by cells to adapt to the medium. We provide the thermodynamic curation of the human GEMs Recon2 and Recon3D and we apply the redHUMAN workflow to derive leukemia-specific reduced models. The reduced models are powerful platforms for studying metabolic differences between phenotypes, such as diseased and healthy cells.


Assuntos
Genoma Humano , Metabolismo/genética , Modelos Biológicos , Biomassa , Vias Biossintéticas , Meios de Cultura , Humanos , Redes e Vias Metabólicas/genética , Reprodutibilidade dos Testes , Estatística como Assunto , Termodinâmica
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