Evaluating PrediXcan’s Ability to Predict Differential Expression Between Alcoholics and Non-Alcoholics

PrediXcan is a recent software for the imputation of gene expression from genotype data alone. Using an overlapping set of transcriptome datasets from postmortem brain tissues of donors with alcohol use disorder and neurotypical controls, which were generated by two different platforms (e.g., Arraystar and Affymetrix), and an additional unrelated transcriptome dataset from lung tissue, we sought to evaluate PrediXcan’s ability to impute gene expression and identify differentially expressed genes. From the Arraystar platform, 1.3% of matched genes between the measured and imputed expression had a Pearson correlation ≥ 0.5. Our attempt to replicate this finding using the expression data from the Affymetrix platform also lead to a similarly poor outcome (2.7%). Our third attempt using the transcriptome data from lung tissue produced similar results (1.1%) but performance improved markedly after filtering out genes with a low predicted R2, which was a model metric provided by the PrediXcan authors. For example, filtering out genes with a predicted R2 below 0.6 led to 16 genes remaining and a Pearson correlation of 0.365 between the measured and imputed expression. We were unable to reproduce similar performance gains with filtering the Arraystar or Affymetrix alcohol use disorder datasets. Given that PrediXcan can impute a narrow portion of the transcriptome, which is further reduced significantly by filtering, we believe caution is warranted with the interpretation of results derived from PrediXcan

Recent Decisions

CHOICE OF LAW--WRONGFUL DEATH--GOVERNMENTAL-INTEREST ANALYSIS DETERMINES LAW APPLICABLE TO MEASURE OF DAMAGES IN CLAIMS ARISING FROM FOREIGN Air CRASH John Edison Drake =============== EUROPEAN COMMUNITIES--FREE MOVEMENT OF WORKERS--COURT OF JUSTICE SETS GUIDELINES FOR USE BY MEMBER STATES OF THE PUBLIC POLICY EXCEPTION IN ARTICLE 48 Heidi A. Rohrbach ================ TAX TREATIES--UNITED STATES MAY USE THE INTERNAL REVENUE CODE SUMMONING AUTHORITY TO OBTAIN DOMESTIC INFORMATION SOLELY TO AID A FOREIGN DOMESTIC TAX INVESTIGATION PURSUANT TO A TAX TREATY John R. Hellinger ============== TREATY INTERPRETATION--WARSAW CONVENTION-- PASSENGERS UNDERGOING SEARCH PREREQUISITE TO BOARDING ARE ENGAGED IN OPERATIONS OF EMBARKING Elizabeth Graeme Brownin

Subtype diversity and reassortment potential for co‐circulating avian influenza viruses at a diversity hot spot

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106946/1/jane12167.pd

Титульные страницы и содержание

Avian influenza viruses (AIVs) have been pivotal to the origination of human pandemic strains. Despite their scientific and public health significance, however, there remains much to be understood about the ecology and evolution of AIVs in wild birds, where major pools of genetic diversity are generated and maintained. Here, we present comparative phylodynamic analyses of human and AIVs in North America, demonstrating (i) significantly higher standing genetic diversity and (ii) phylogenetic trees with a weaker signature of immune escape in AIVs than in human viruses. To explain these differences, we performed statistical analyses to quantify the relative contribution of several potential explanations. We found that HA genetic diversity in avian viruses is determined by a combination of factors, predominantly subtype-specific differences in host immune selective pressure and the ecology of transmission (in particular, the durability of subtypes in aquatic environments). Extending this analysis using a computational model demonstrated that virus durability may lead to long-term, indirect chains of transmission that, when coupled with a short host lifespan, can generate and maintain the observed high levels of genetic diversity. Further evidence in support of this novel finding was found by demonstrating an association between subtype-specific environmental durability and predicted phylogenetic signatures: genetic diversity, variation in phylogenetic tree branch lengths, and tree height. The conclusion that environmental transmission plays an important role in the evolutionary biology of avian influenza viruses—a manifestation of the “storage effect”—highlights the potentially unpredictable impact of wildlife reservoirs for future human pandemics and the need for improved understanding of the natural ecology of these viruses

VOYAGER OBSERVATIONS OF MAGNETIC SECTORS AND HELIOSPHERIC CURRENT SHEET CROSSINGS IN THE OUTER HELIOSPHERE

Voyager 1 (V1) has passed through the heliosheath and is in the local interstellar medium. Voyager 2 (V2) has been in the heliosheath since 2007. The role of reconnection in the heliosheath is under debate; compression of the heliospheric current sheets (HCS) in the heliosheath could lead to rapid reconnection and a reconfiguration of the magnetic field topology. This paper compares the expected and actual amounts of time the Voyager spacecraft observe each magnetic sector and the number of HCS crossings. The predicted and observed values generally agree well. One exception is at Voyager 1 in 2008 and 2009, where the distribution of sectors is more equal than expected and the number of HCS crossings is small. Two other exceptions are at V1 in 2011–2012 and at V2 in 2012, when the spacecraft are in the opposite magnetic sector less than expected and see fewer HCS crossings than expected. These features are consistent with those predicted for reconnection, and consequently searches for other reconnection signatures should focus on these times.National Aeronautics and Space Administration (Contract 959203)Massachusetts Institute of Technology. Jet Propulsion Laborator

Montane Temperate-Boreal Forests Retain the Leaf Economic Spectrum Despite Intraspecific Variability

Trait-based analyses provide powerful tools for developing a generalizable, physiologically grounded understanding of how forest communities are responding to ongoing environmental changes. Key challenges lie in (1) selecting traits that best characterize the ecological performance of species in the community and (2) determining the degree and importance of intraspecific variability in those traits. Recent studies suggest that globally evident trait correlations (trait dimensions), such as the leaf economic spectrum, may be weak or absent at local scales. Moreover, trait-based analyses that utilize a mean value to represent a species may be misleading. Mean trait values are particularly problematic if species trait value rankings change along environmental gradients, resulting in species trait crossover. To assess how plant traits (1) covary at local spatial scales, (2) vary across the dominant environmental gradients, and (3) can be partitioned within and across taxa, we collected data on 9 traits for 13 tree species spanning the montane temperate—boreal forest ecotones of New York and northern New England. The primary dimension of the trait ordination was the leaf economic spectrum, with trait variability among species largely driven by differences between deciduous angiosperms and evergreen gymnosperms. A second dimension was related to variability in nitrogen to phosphorous levels and stem specific density. Levels of intraspecific trait variability differed considerably among traits, and was related to variation in light, climate, and tree developmental stage. However, trait rankings across species were generally conserved across these gradients and there was little evidence of species crossover. The persistence of the leaf economics spectrum in both temperate and high-elevation conifer forests suggests that ecological strategies of tree species are associated with trade-offs between resource acquisition and tolerance, and may be quantified with relatively few traits. Furthermore, the assumption that species may be represented with a single trait value may be warranted for some trait-based analyses provided traits were measured under similar light levels and climate conditions

Dissecting a wildlife disease hotspot: the impact of multiple host species, environmental transmission and seasonality in migration, breeding and mortality

Avian influenza viruses (AIVs) have been implicated in all human influenza pandemics in recent history. Despite this, surprisingly little is known about the mechanisms underlying the maintenance and spread of these viruses in their natural bird reservoirs. Surveillance has identified an AIV ‘hotspot’ in shorebirds at Delaware Bay, in which prevalence is estimated to exceed other monitored sites by an order of magnitude. To better understand the factors that create an AIV hotspot, we developed and parametrized a mechanistic transmission model to study the simultaneous epizootiological impacts of multi-species transmission, seasonal breeding, host migration and mixed transmission routes. We scrutinized our model to examine the potential for an AIV hotspot to serve as a ‘gateway’ for the spread of novel viruses into North America. Our findings identify the conditions under which a novel influenza virus, if introduced into the system, could successfully invade and proliferate

Dissecting a wildlife disease hotspot: the impact of multiple host species, environmental transmission and seasonality in migration, breeding and mortality

Avian influenza viruses (AIVs) have been implicated in all human influenza pandemics in recent history. Despite this, surprisingly little is known about the mechanisms underlying the maintenance and spread of these viruses in their natural bird reservoirs. Surveillance has identified an AIV ‘hotspot’ in shorebirds at Delaware Bay, in which prevalence is estimated to exceed other monitored sites by an order of magnitude. To better understand the factors that create an AIV hotspot, we developed and parametrized a mechanistic transmission model to study the simultaneous epizootiological impacts of multi-species transmission, seasonal breeding, host migration and mixed transmission routes. We scrutinized our model to examine the potential for an AIV hotspot to serve as a ‘gateway’ for the spread of novel viruses into North America. Our findings identify the conditions under which a novel influenza virus, if introduced into the system, could successfully invade and proliferate