An Information-Theoretic Machine Learning Approach to Expression QTL Analysis

Expression Quantitative Trait Locus (eQTL) analysis is a powerful tool to study the biological mechanisms linking the genotype with gene expression. Such analyses can identify genomic locations where genotypic variants influence the expression of genes, both in close proximity to the variant (cis-eQTL), and on other chromosomes (trans-eQTL). Many traditional eQTL methods are based on a linear regression model. In this study, we propose a novel method by which to identify eQTL associations with information theory and machine learning approaches. Mutual Information (MI) is used to describe the association between genetic marker and gene expression. MI can detect both linear and non-linear associations. What’s more, it can capture the heterogeneity of the population. Advanced feature selection methods, Maximum Relevance Minimum Redundancy (mRMR) and Incremental Feature Selection (IFS), were applied to optimize the selection of the affected genes by the genetic marker. When we applied our method to a study of apoE-deficient mice, it was found that the cis-acting eQTLs are stronger than trans-acting eQTLs but there are more trans-acting eQTLs than cis-acting eQTLs. We compared our results (mRMR.eQTL) with R/qtl, and MatrixEQTL (modelLINEAR and modelANOVA). In female mice, 67.9% of mRMR.eQTL results can be confirmed by at least two other methods while only 14.4% of R/qtl result can be confirmed by at least two other methods. In male mice, 74.1% of mRMR.eQTL results can be confirmed by at least two other methods while only 18.2% of R/qtl result can be confirmed by at least two other methods. Our methods provide a new way to identify the association between genetic markers and gene expression. Our software is available from supporting information.     

Linguistic Anthropology in 2008: An Election-Cycle Guide

ABSTRACT   Loosely following the structure of the U.S. election cycle, I identify some of the more important institutions and events that have recently served as venues for field-building scholarly practices and processes in linguistic anthropology. I examine various trends and concerns animating recent publications on language and social life. I discuss the ongoing impact on the field of recent major works that attempt to codify methodological and theoretical approaches to the intersection of language and society. I also consider some of linguistic anthropology's emergent ventures, including new collaborative projects and new proposals for interdisciplinary work. Finally, I discuss some of the political implications of academic specialization, disciplinary boundaries, and impending "generational shift," both in the subdiscipline and the academy generally. I close by raising questions about future directions and possibilities for research in linguistic anthropology and other interdisciplinary enterprises. [Keywords: linguistic anthropology, interdisciplinarity, linguistic ideology, semiotic practices, linguistic variation]     

Profiling of Intracellular Metabolites: An Approach to Understanding the Characteristic Physiology of Mycobacterium leprae

Mycobacterium leprae is the causative agent of leprosy and also known to possess unique features such as inability to proliferate in vitro. Among the cellular components of M. leprae, various glycolipids present on the cell envelope are well characterized and some of them are identified to be pathogenic factors responsible for intracellular survival in host cells, while other intracellular metabolites, assumed to be associated with basic physiological feature, remain largely unknown. In the present study, to elucidate the comprehensive profile of intracellular metabolites, we performed the capillary electrophoresis-mass spectrometry (CE-MS) analysis on M. leprae and compared to that of M. bovis BCG. Interestingly, comparison of these two profiles showed that, in M. leprae, amino acids and their derivatives are significantly accumulated, but most of intermediates related to central carbon metabolism markedly decreased, implying that M. leprae possess unique metabolic features. The present study is the first report demonstrating the unique profiles of M. leprae metabolites and these insights might contribute to understanding undefined metabolism of M. leprae as well as pathogenic characteristics related to the manifestation of the disease.     

Health Effects of Lesion Localization in Multiple Sclerosis: Spatial Registration and Confounding Adjustment

Brain lesion localization in multiple sclerosis (MS) is thought to be associated with the type and severity of adverse health effects. However, several factors hinder statistical analyses of such associations using large MRI datasets: 1) spatial registration algorithms developed for healthy individuals may be less effective on diseased brains and lead to different spatial distributions of lesions; 2) interpretation of results requires the careful selection of confounders; and 3) most approaches have focused on voxel-wise regression approaches. In this paper, we evaluated the performance of five registration algorithms and observed that conclusions regarding lesion localization can vary substantially with the choice of registration algorithm. Methods for dealing with confounding factors due to differences in disease duration and local lesion volume are introduced. Voxel-wise regression is then extended by the introduction of a metric that measures the distance between a patient-specific lesion mask and the population prevalence map.     

Lifespan Modulation in Mice and the Confounding Effects of Genetic Background

We are currently in the midst of a revolution in ageing research,with several dietary,genetic and pharmacological interventions now known to modulate ageing in model organisms.Excitingly,these interventions also appear to have beneficial effects on late-life health.For example,dietary restriction(DR) has been shown to slow the incidence of age-associated cardiovascular disease,metabolic disease,cancer and brain ageing in non-human primates and has been shown to improve a range of health indices in humans.While the idea that DR's ability to extend lifespan is often thought of as being universal,studies in a range of organisms,including yeast,mice and monkeys,suggest that this may not actually be the case.The precise reasons underlying these differential effects of DR on lifespan are currently unclear,but genetic background may be an important factor in how an individual responds to DR.Similarly,recent findings also suggest that the responsiveness of mice to specific genetic or pharmacological interventions that modulate ageing may again be influenced by genetic background.Consequently,while there is a clear driver to develop interventions to improve late-life health and vitality,understanding precisely how these act in response to particular genotypes is critical if we are to translate these findings to humans.We will consider of the role of genetic background in the efficacy of various lifespan interventions and discuss potential routes of utilising genetic heterogeneity to further understand how particular interventions modulate lifespan and healthspan.     

An Integrated Approach of Fuzzy Linguistic Preference Based AHP and Fuzzy COPRAS for Machine Tool Evaluation

Globalization of business and competitiveness in manufacturing has forced companies to improve their manufacturing facilities to respond to market requirements. Machine tool evaluation involves an essential decision using imprecise and vague information, and plays a major role to improve the productivity and flexibility in manufacturing. The aim of this study is to present an integrated approach for decision-making in machine tool selection. This paper is focused on the integration of a consistent fuzzy AHP (Analytic Hierarchy Process) and a fuzzy COmplex PRoportional ASsessment (COPRAS) for multi-attribute decision-making in selecting the most suitable machine tool. In this method, the fuzzy linguistic reference relation is integrated into AHP to handle the imprecise and vague information, and to simplify the data collection for the pair-wise comparison matrix of the AHP which determines the weights of attributes. The output of the fuzzy AHP is imported into the fuzzy COPRAS method for ranking alternatives through the closeness coefficient. Presentation of the proposed model application is provided by a numerical example based on the collection of data by questionnaire and from the literature. The results highlight the integration of the improved fuzzy AHP and the fuzzy COPRAS as a precise tool and provide effective multi-attribute decision-making for evaluating the machine tool in the uncertain environment.     

Understanding Collective Discontents: A Psychological Approach to Measuring Zeitgeist

Over the last decade, several countries around the world developed a collective sense of doom and gloom: Their Zeitgeist could be characterized as one of decline. Paradoxically, in some countries, such as the Netherlands, this collective discontent with society seems to exist despite high levels of individual well-being. Current psychological research informs us about why individuals would feel unduly optimistic, but does not account for a collective sense of decline. The present research develops a novel operationalization of Zeitgeist, referred to as a general factor Z. We conceptualize Zeitgeist as a collective global-level evaluation of the state (and future) of society. Three studies confirm that perceptions of the same societal problems at the personal and collective level differed strongly. Across these studies we found support for a hypothesized latent factor Z, underlying collective-level perceptions of society. This Z-factor predicted people’s interpretation of new information about society that was presented through news stories. These results provide a first step in operationalizing and (ultimately) understanding the concept of Zeitgeist: collectively shared ideas about society. Implications for policy are discussed.     

Confounding factors in diagnosing brain death: a case report

Background  

Brain death is strictly defined medically and legally. This diagnosis depends on three cardinal neurological features: coma, absent brainstem reflexes, and apnea. The diagnosis can only be made, however, in the absence of intoxication, hypothermia, or certain medical illnesses.     

Effects of Silicone-Bond Sediment on the Growth of Aquatic Macrophytes: An Experimental Approach

In this study the effect of silicone on the growth of aquatic macrophytes was examined for a three-week period in laboratory conditions with the use of three different macrophyte species. Three pot treatments—high silicone added, low silicone added, and control—each with three replicate buckets, were used. The RGR of both Myriophyllum verticillatum L. and Potamogeton gramineus L. differed significantly between treatments (p < 0.001 and p < 0.001 respectively). However, the RGR of Ceratophyllum demersum L. did not differ (p = 0.124). In the control group, M. verticillatum and P. gramineus grew well and produce more lateral shoots and longer roots than in the high and low silicone-added treatments.     

Understanding Long-Term Changes in Species Abundance Using a Niche-Based Approach

One of the major challenges to understanding population changes in ecology for assessment purposes is the difficulty in evaluating the suitability of an area for a given species. Here we used a new simple approach able to faithfully predict through time the abundance of two key zooplanktonic species by focusing on the relationship between the species’ environmental preferences and their observed abundances. The approach is applied to the marine copepods Calanus finmarchicus and C. helgolandicus as a case study characterising the multidecadal dynamics of the North Sea ecosystem. We removed all North Sea data from the Continuous Plankton Recorder (CPR) dataset and described for both species a simplified ecological niche using Sea Surface Temperature (SST) and CPR Phytoplankton Colour Index (PCI). We then modelled the dynamics of each species by associating the North Sea’s environmental parameters to the species’ ecological niches, thus creating a method to assess the suitability of this area. By using both C. finmarchicus and C. helgolandicus as indicators, the procedure reproduces the documented switches from cold to warm temperate states observed in the North Sea.     

An Experimental Approach to the Effects of Predictability on Community Structure

This paper considers the effects of different levels of resourcepredictability on niche widths, competition and diversity ina community of three hummingbird species. Three pairs of hypothesesare tested: whether decreasing predictability (a) increasesor decreases niche width, (b) increases or decreases competitionand (c) increases or decreases diversity. The results show thatcomplementary increases and decreases in niche width occur withdecreasing predictability, while competition and diversity decrease,at least with extreme unpredictability. A model, which assumesthe species to have similar resource preferences, and its predictionsare examined. The dominant species, Lampornis clemenciae, excludes a subordinatespecies, Archilochus alexandri, from preferred resources. Thisdefense becomes unprofitable with decreasing predictabilityand Archilochus invades the resources once vigorously defendedby Lampornis. When the spectrum of resources is altered in thedirection of decreasing suitability for both species, Lampornisbecomes even more specialized and sensitive to the effects ofunpredictability. A third species, Eugenes fulgens, steals resourcesundefended by Lampornis. These characteristics seem to be commonto a number of communities in very different taxonomic groups,and characteristic of communities in which species share a commonpreferred resource. The question of how a community organizedwith distinct resource preferences responds to decreasing predictabilityremains open.