Tissue-specific network-based genome wide study of amygdala imaging phenotypes to identify functional interaction modules

Motivation: Network-based genome-wide association studies (GWAS) aim to identify functional modules from biological networks that are enriched by top GWAS findings. Although gene functions are relevant to tissue context, most existing methods analyze tissue-free networks without reflecting phenotypic specificity. Results: We propose a novel module identification framework for imaging genetic studies using the tissue-specific functional interaction network. Our method includes three steps: (i) re-prioritize imaging GWAS findings by applying machine learning methods to incorporate network topological information and enhance the connectivity among top genes; (ii) detect densely connected modules based on interactions among top re-prioritized genes; and (iii) identify phenotype-relevant modules enriched by top GWAS findings. We demonstrate our method on the GWAS of [18F]FDG-PET measures in the amygdala region using the imaging genetic data from the Alzheimer's Disease Neuroimaging Initiative, and map the GWAS results onto the amygdala-specific functional interaction network. The proposed network-based GWAS method can effectively detect densely connected modules enriched by top GWAS findings. Tissue-specific functional network can provide precise context to help explore the collective effects of genes with biologically meaningful interactions specific to the studied phenotype

Diatom based transfer function for estimating the chemical composition of fossil water. Calibration based on salt lakes of the Lipez area in the southwestern Bolivian Altiplano

Diatom assemblages and water chemistry were studied in 13 shallow salt lakes in the southern part of the Bolivian Altiplano. At each locality bottom sediment and water samples were collected simultaneously. Relationships between the composition of the diatom assemblages and variations in water chemistry were collated in order to permit the estimation of ancient water chemistries based on changes in the make up of fossil diatom associations in older sediments. Weighted Averages treated by Partial Least Squares regression (WA and WA-PLS methods) allowed an estimation of optima and the relative tolerances of 61 species to variations in salinity and to the relative quantities of the 15 chemical elements studied, among them boron and lithium.L'étude des assemblages de diatomées et de la composition chimique des eaux a été effectuée dans 13 lacs salés peu profonds localisés dans le Sud de l'Altiplano Bolivien. Les points et les dates de prélèvement sont les mêmes pour les deux types d'étude. Les relations entre les assemblages de diatomées et les variables chimiques mesurées sont effectuées dans le but d'estimer ces variables dans le passé à partir des diatomées fossiles conservées dans les sédiments. La méthode des moyennes pondérées (WA et WA-PLS régression) a permis d'estimer les optima et les tolérances de 61 espèces à la salinité et aux différents éléments chimiques dont le bore et le lithium

Type 2 diabetes mellitus and cerebrospinal fluid Alzheimer's disease biomarker amyloid β1-42 in Alzheimer's Disease Neuroimaging Initiative participants

Introduction Type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer's disease. Cerebrospinal fluid (CSF) amyloid β (Aβ) 1-42 is an important Alzheimer's disease biomarker. However, it is inconclusive on how T2DM is related to CSF Aβ1-42. Methods Participants with T2DM were selected from the Alzheimer's Disease Neuroimaging Initiative by searching keywords from the medical history database. A two-way analysis of covariance model was used to analyze how T2DM associates with CSF Aβ1-42 or cerebral cortical Aβ. Results CSF Aβ1-42 was higher in the T2DM group than the nondiabetic group. The inverse relation between CSF Aβ1-42 and cerebral cortical Aβ was independent of T2DM status. Participants with T2DM had a lower cerebral cortical Aβ in anterior cingulate, precuneus, and temporal lobe than controls. Discussion T2DM is positively associated with CSF Aβ1-42 but negatively with cerebral cortical Aβ. The decreased cerebral cortical Aβ associated with T2DM is preferentially located in certain brain regions

High-J CO emission in the Cepheus E protostellar outflow observed with SOFIA/GREAT

We present and analyze two spectrally resolved high-J CO lines towards the molecular outflow Cep E, driven by an intermediate-mass class 0 protostar. Using the GREAT receiver on board SOFIA, we observed the CO (12--11) and (13--12) transitions (E_u ~ 430 and 500 K, respectively) towards one position in the blue lobe of this outflow, that had been known to display high-velocity molecular emission. We detect the outflow emission in both transitions, up to extremely high velocities (~ 100 km/s with respect to the systemic velocity). We divide the line profiles into three velocity ranges that each have interesting spectral features: standard, intermediate, and extremely high-velocity. One distinct bullet is detected in each of the last two. A large velocity gradient analysis for these three velocity ranges provides constraints on the kinetic temperature and volume density of the emitting gas, >~ 100 K and > ~ 10^4 cm^-3, respectively. These results are in agreement with previous ISO observations and are comparable with results obtained by Herschel for similar objects. We conclude that high-J CO lines are a good tracer of molecular bullets in protostellar outflows. Our analysis suggests that different physical conditions are at work in the intermediate velocity range compared with the standard and extremely high-velocity gas at the observed position.Comment: Accepted for publication in A&A (SOFIA/GREAT special issue

Probing MHD Shocks with high-J CO observations: W28F

Context. Observing supernova remnants (SNRs) and modelling the shocks they are associated with is the best way to quantify the energy SNRs re-distribute back into the Interstellar Medium (ISM). Aims. We present comparisons of shock models with CO observations in the F knot of the W28 supernova remnant. These comparisons constitute a valuable tool to constrain both the shock characteristics and pre-shock conditions. Methods. New CO observations from the shocked regions with the APEX and SOFIA telescopes are presented and combined. The integrated intensities are compared to the outputs of a grid of models, which were combined from an MHD shock code that calculates the dynamical and chemical structure of these regions, and a radiative transfer module based on the 'large velocity gradient' (LVG) approximation. Results. We base our modelling method on the higher J CO transitions, which unambiguously trace the passage of a shock wave. We provide fits for the blue- and red-lobe components of the observed shocks. We find that only stationary, C-type shock models can reproduce the observed levels of CO emission. Our best models are found for a pre-shock density of 104 cm-3, with the magnetic field strength varying between 45 and 100 {\mu}G, and a higher shock velocity for the so-called blue shock (\sim25 km s-1) than for the red one (\sim20 km s-1). Our models also satisfactorily account for the pure rotational H2 emission that is observed with Spitzer.Comment: 8 pages, 6 figures, 1 table, accepted for A&A SOFIA/GREAT Special Issu

Network-Based Analysis of Genetic Variants Associated with Hippocampal Volume in Alzheimer’S Disease: A Study of Adni Cohorts

Background: Alzheimer’s disease (AD) is a neurodegenerative disease that causes dementia. While molecular basis of AD is not fully understood, genetic factors are expected to participate in the development and progression of the disease. Our goal was to uncover novel genetic underpinnings of Alzheimer’s disease with a bioinformatics approach that accounts for tissue specificity. Findings: We performed genome-wide association studies (GWAS) for hippocampal volume in two Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohorts. We used these GWAS in a subsequent tissue-specific network-wide association study (NetWAS), which applied nominally significant associations in the initial GWAS to identify disease relevant patterns in a functional network for the hippocampus. We compared prioritized gene lists from NetWAS and GWAS with literature curated AD-associated genes from the Online Mendelian Inheritance in Man (OMIM) database. In the ADNI-1 GWAS, where we also observed an enrichment of low p-values, NetWAS prioritized disease-gene associations in accordance with OMIM annotations. This was not observed in the ADNI-2 dataset. We provide source code to replicate these analyses as well as complete results under permissive licenses. Conclusions: We performed the first analysis of hippocampal volume using NetWAS, which uses machine learning algorithms applied to tissue-specific functional interaction network to prioritize GWAS results. Our findings support the idea that tissue-specific networks may provide helpful context for understanding the etiology of common human diseases and reveal challenges that network-based approaches encounter in some datasets. Our source code and intermediate results files can facilitate the development of methods to address these challenges

Identifying disease sensitive and quantitative trait-relevant biomarkers from multidimensional heterogeneous imaging genetics data via sparse multimodal multitask learning

Motivation: Recent advances in brain imaging and high-throughput genotyping techniques enable new approaches to study the influence of genetic and anatomical variations on brain functions and disorders. Traditional association studies typically perform independent and pairwise analysis among neuroimaging measures, cognitive scores and disease status, and ignore the important underlying interacting relationships between these units

Detection of 6.7 GHz methanol absorption towards hot corinos

Methanol masers at 6.7 GHz have been found exclusively towards high-mass star forming regions. Recently, some Class 0 protostars have been found to display conditions similar to what are found in hot cores that are associated with massive star formation. These hot corino sources have densities, gas temperatures, and methanol abundances that are adequate for exciting strong 6.7 GHz maser emission. This raises the question of whether 6.7 GHz methanol masers can be found in both hot corinos and massive star forming regions, and if not, whether thermal methanol emission can be detected. We searched for the 6.7 GHz methanol line towards five hot corino sources in the Perseus region using the Arecibo radio telescope. To constrain the excitation conditions of methanol, we observed thermal submillimeter lines of methanol in the NGC1333-IRAS 4 region with the APEX telescope. We did not detect 6.7 GHz emission in any of the sources, but found absorption against the cosmic microwave background in NGC1333-IRAS 4A and NGC1333-IRAS 4B. Using a large velocity gradient analysis, we modeled the excitation of methanol over a wide range of physical parameters, and verify that the 6.7 GHz line is indeed strongly anti-inverted for densities lower than 10^6 cm^-3. We used the submillimeter observations of methanol to verify the predictions of our model for IRAS 4A by comparison with other CH3OH transitions. Our results indicate that the methanol observations from the APEX and Arecibo telescopes are consistent with dense (n ~ 10^6 cm^-3), cold (T ~ 15-30 K) gas. The lack of maser emission in hot corinos and low-mass protostellar objects in general may be due to densities that are much higher than the quenching density in the region where the radiation field is conducive to maser pumping.Comment: Accepted by A&

A multi-transition submillimeter water maser study of evolved stars - detection of a new line near 475 GHz

Context: Maser emission from the H2O molecule probes the warm, inner circumstellar envelopes of oxygen-rich red giant and supergiant stars. Multi-maser transition studies can be used to put constraints on the density and temperature of the emission regions. Aims: A number of known H2O maser lines were observed toward the long period variables R Leo and W Hya and the red supergiant VY CMa. A search for a new, not yet detected line near 475 GHz was conducted toward these stars. Methods: The Atacama Pathfinder Experiment telescope was used for a multi-transition observational study of submillimeter H2O lines. Results: The 5_33-4_40 transition near 475 GHz was clearly detected toward VY CMa and W Hya. Many other H2O lines were detected toward all three target stars. Relative line intensity ratios and velocity widths were found to vary significantly from star to star. Conclusions: Maser action is observed in all but one line for which it was theoretically predicted. In contrast, one of the strongest maser lines, in R Leo by far the strongest, the 437 GHz 7_53-6_60 transition, is not predicted to be inverted. Some other qualitative predictions of the model calculations are at variance with our observations. Plausible reasons for this are discussed. Based on our findings for W Hya and VY CMa, we find evidence that the H2O masers in the AGB star W Hya arise from the regular circumstellar outflow, while shock excitation in a high velocity flow seems to be required to excite masers far from the red supergiant VY CMa.Comment: 9 pages, 4 figures, Astronomy and Astrophyics (in press