Metabolomic and proteomic profiling in bipolar disorder patients revealed potential molecular signatures related to hemostasis.

INTRODUCTION: Bipolar disorder (BD) is a mood disorder characterized by the occurrence of depressive episodes alternating with episodes of elevated mood (known as mania). There is also an increased risk of other medical comorbidities. OBJECTIVES: This work uses a systems biology approach to compare BD treated patients with healthy controls (HCs), integrating proteomics and metabolomics data using partial correlation analysis in order to observe the interactions between altered proteins and metabolites, as well as proposing a potential metabolic signature panel for the disease. METHODS: Data integration between proteomics and metabolomics was performed using GC-MS data and label-free proteomics from the same individuals (N = 13; 5 BD, 8 HC) using generalized canonical correlation analysis and partial correlation analysis, and then building a correlation network between metabolites and proteins. Ridge-logistic regression models were developed to stratify between BD and HC groups using an extended metabolomics dataset (N = 28; 14 BD, 14 HC), applying a recursive feature elimination for the optimal selection of the metabolites. RESULTS: Network analysis demonstrated links between proteins and metabolites, pointing to possible alterations in hemostasis of BD patients. Ridge-logistic regression model indicated a molecular signature comprising 9 metabolites, with an area under the receiver operating characteristic curve (AUROC) of 0.833 (95% CI 0.817-0.914). CONCLUSION: From our results, we conclude that several metabolic processes are related to BD, which can be considered as a multi-system disorder. We also demonstrate the feasibility of partial correlation analysis for integration of proteomics and metabolomics data in a case-control study setting.

Learning genetic and environmental graphical models from family data.

Many challenging problems in biomedical research rely on understanding how variables are associated with each other and influenced by genetic and environmental factors. Probabilistic graphical models (PGMs) are widely acknowledged as a very natural and formal language to describe relationships among variables and have been extensively used for studying complex diseases and traits. In this work, we propose methods that leverage observational Gaussian family data for learning a decomposition of undirected and directed acyclic PGMs according to the influence of genetic and environmental factors. Many structure learning algorithms are strongly based on a conditional independence test. For independent measurements of normally distributed variables, conditional independence can be tested through standard tests for zero partial correlation. In family data, the assumption of independent measurements does not hold since related individuals are correlated due to mainly genetic factors. Based on univariate polygenic linear mixed models, we propose tests that account for the familial dependence structure and allow us to assess the significance of the partial correlation due to genetic (between-family) factors and due to other factors, denoted here as environmental (within-family) factors, separately. Then, we extend standard structure learning algorithms, including the IC/PC and the really fast causal inference (RFCI) algorithms, to Gaussian family data. The algorithms learn the most likely PGM and its decomposition into two components, one explained by genetic factors and the other by environmental factors. The proposed methods are evaluated by simulation studies and applied to the Genetic Analysis Workshop 13 simulated dataset, which captures significant features of the Framingham Heart Study.

Disruption of transfer entropy and inter-hemispheric brain functional connectivity in patients with disorder of consciousness.

Severe traumatic brain injury can lead to disorders of consciousness (DOC) characterized by deficit in conscious awareness and cognitive impairment including coma, vegetative state, minimally consciousness, and lock-in syndrome. Of crucial importance is to find objective markers that can account for the large-scale disturbances of brain function to help the diagnosis and prognosis of DOC patients and eventually the prediction of the coma outcome. Following recent studies suggesting that the functional organization of brain networks can be altered in comatose patients, this work analyzes brain functional connectivity (FC) networks obtained from resting-state functional magnetic resonance imaging (rs-fMRI). Two approaches are used to estimate the FC: the Partial Correlation (PC) and the Transfer Entropy (TE). Both the PC and the TE show significant statistical differences between the group of patients and control subjects; in brief, the inter-hemispheric PC and the intra-hemispheric TE account for such differences. Overall, these results suggest two possible rs-fMRI markers useful to design new strategies for the management and neuropsychological rehabilitation of DOC patients.

Size and shape in Melipona quadrifasciata anthidioides Lepeletier, 1836 (Hymenoptera; Meliponini) / Tamanho e forma em Melipona quadrifasciata anthidioides Lepeletier, 1836 (Hymenoptera; Meliponini)

This study aimed to identify differences in wing shape among populations of Melipona quadrifasciata anthidioides obtained in 23 locations in the semi-arid region of Bahia state (Brazil). Analysis of the Procrustes distances among mean wing shapes indicated that population structure did not determine shape variation. Instead, populations were structured geographically according to wing size. The Partial Mantel Test between morphometric (shape and size) distance matrices and altitude, taking geographic distances into account, was used for a more detailed understanding of size and shape determinants. A partial Mantel test between morphometris (shape and size) variation and altitude, taking geographic distances into account, revealed that size (but not shape) is largely influenced by altitude (r = 0.54 p 0.01). These results indicate greater evolutionary constraints for the shape variation, which must be directly associated with aerodynamic issues in this structure. The size, however, indicates that the bees tend to have larger wings in populations located at higher altitudes.(AU)

Este trabalho avaliou a divergência de forma entre populações de Melipona quadrifasciata anthidioides, utilizando caracteres morfométricos em 23 localidades da região semi-árida do estado da Bahia (Brasil). As análises das distâncias de Procrustes entre as formas médias das asas indicaram que não há estruturação populacional para a variação dessa estrutura. Entretanto, nossas análises demonstraram que as populações estavam estruturadas geograficamente pelo tamanho das asas. O teste parcial de Mantel entre matrizes de distâncias morfométricas (forma e tamanho) e altitude, levando em conta as distâncias geográficas, foi utilizado para uma compreensão mais detalhada dos determinantes de tamanho e forma. O teste de Mantel entre as variações morfométricas (forma e tamanho) e altitude, tendo em conta as distâncias geográficas, revelou que o tamanho (mas não a forma) é amplamente influenciado pela altitude (r = 0,54 p 0,01). Tais resultados indicam maiores restrições evolutivas para a variação de forma, o que deve estar diretamente associado às questões aerodinâmicas dessa estrutura. O tamanho, por outro lado, indica que as abelhas estudadas tendem a apresentar asas maiores nas populações localizadas em regiões de maior altitude.(AU)

Size and shape in Melipona quadrifasciata anthidioides Lepeletier, 1836 (Hymenoptera; Meliponini) / Tamanho e forma em Melipona quadrifasciata anthidioides Lepeletier, 1836 (Hymenoptera; Meliponini)

This study aimed to identify differences in wing shape among populations of Melipona quadrifasciata anthidioides obtained in 23 locations in the semi-arid region of Bahia state (Brazil). Analysis of the Procrustes distances among mean wing shapes indicated that population structure did not determine shape variation. Instead, populations were structured geographically according to wing size. The Partial Mantel Test between morphometric (shape and size) distance matrices and altitude, taking geographic distances into account, was used for a more detailed understanding of size and shape determinants. A partial Mantel test between morphometris (shape and size) variation and altitude, taking geographic distances into account, revealed that size (but not shape) is largely influenced by altitude (r = 0.54 p 0.01). These results indicate greater evolutionary constraints for the shape variation, which must be directly associated with aerodynamic issues in this structure. The size, however, indicates that the bees tend to have larger wings in populations located at higher altitudes.

Este trabalho avaliou a divergência de forma entre populações de Melipona quadrifasciata anthidioides, utilizando caracteres morfométricos em 23 localidades da região semi-árida do estado da Bahia (Brasil). As análises das distâncias de Procrustes entre as formas médias das asas indicaram que não há estruturação populacional para a variação dessa estrutura. Entretanto, nossas análises demonstraram que as populações estavam estruturadas geograficamente pelo tamanho das asas. O teste parcial de Mantel entre matrizes de distâncias morfométricas (forma e tamanho) e altitude, levando em conta as distâncias geográficas, foi utilizado para uma compreensão mais detalhada dos determinantes de tamanho e forma. O teste de Mantel entre as variações morfométricas (forma e tamanho) e altitude, tendo em conta as distâncias geográficas, revelou que o tamanho (mas não a forma) é amplamente influenciado pela altitude (r = 0,54 p 0,01). Tais resultados indicam maiores restrições evolutivas para a variação de forma, o que deve estar diretamente associado às questões aerodinâmicas dessa estrutura. O tamanho, por outro lado, indica que as abelhas estudadas tendem a apresentar asas maiores nas populações localizadas em regiões de maior altitude.

Mantel test in population genetics.

The comparison of genetic divergence or genetic distances, estimated by pairwise FST and related statistics, with geographical distances by Mantel test is one of the most popular approaches to evaluate spatial processes driving population structure. There have been, however, recent criticisms and discussions on the statistical performance of the Mantel test. Simultaneously, alternative frameworks for data analyses are being proposed. Here, we review the Mantel test and its variations, including Mantel correlograms and partial correlations and regressions. For illustrative purposes, we studied spatial genetic divergence among 25 populations of Dipteryx alata ("Baru"), a tree species endemic to the Cerrado, the Brazilian savannas, based on 8 microsatellite loci. We also applied alternative methods to analyze spatial patterns in this dataset, especially a multivariate generalization of Spatial Eigenfunction Analysis based on redundancy analysis. The different approaches resulted in similar estimates of the magnitude of spatial structure in the genetic data. Furthermore, the results were expected based on previous knowledge of the ecological and evolutionary processes underlying genetic variation in this species. Our review shows that a careful application and interpretation of Mantel tests, especially Mantel correlograms, can overcome some potential statistical problems and provide a simple and useful tool for multivariate analysis of spatial patterns of genetic divergence.

Associação entre características agronômicas e capacidade de expansão em população de milho pipoca sob seleção recorrente / Association between agronomical traits and popping expansion in a popcorn population under recurrent selection

Objetivou-se, neste trabalho, investigar a possibilidade de seleção mais eficiente por meio do uso de análise de trilha e de correlações parciais no programa de seleção recorrente da população UENF de milho pipoca. Duzentas famílias de irmãos completos foram obtidas e avaliadas quanto a oito características em dois ambientes no estado do Rio de Janeiro: Campos dos Goytacazes e Itaocara. A correlação genotípica entre capacidade de expansão e rendimento de grãos foi negativa e não significativa ao nível de 5 por cento de probabilidade pelo teste t. A análise de trilha demonstrou ser a massa de 100 grãos, a característica mais associada à capacidade de expansão neste estudo. Há possibilidade de obtenção de resposta correlacionada em capacidade de expansão e rendimento de grãos, desde que se selecionem, entre os genótipos de maior rendimento, aqueles com menores tamanhos de grãos.

The objective of this work was to investigate the possibility of a more efficient selection through path analysis and partial correlation in the breeding program of the UENF popcorn population by recurrent selection. Two hundred full-sib progenies were obtained and evaluated by eight traits in two environments in Rio de Janeiro State: Campos dos Goytacazes and Itaocara. The genotypic correlation between popping expansion and grain yield was negative and non significant at the 5 percent probability level by t test. Path analysis showed that mass weight of 100 grains is the most associated trait at popping expansion in this study. It is possible to obtain correlated response for popping expansion by grain yield, as long as genotypes with smaller grain size are selected from the genotypes with higher grain yield.