A quick guide for student-driven community genome annotation

High quality gene models are necessary to expand the molecular and genetic tools available for a target organism, but these are available for only a handful of model organisms that have undergone extensive curation and experimental validation over the course of many years. The majority of gene models present in biological databases today have been identified in draft genome assemblies using automated annotation pipelines that are frequently based on orthologs from distantly related model organisms. Manual curation is time consuming and often requires substantial expertise, but is instrumental in improving gene model structure and identification. Manual annotation may seem to be a daunting and cost-prohibitive task for small research communities but involving undergraduates in community genome annotation consortiums can be mutually beneficial for both education and improved genomic resources. We outline a workflow for efficient manual annotation driven by a team of primarily undergraduate annotators. This model can be scaled to large teams and includes quality control processes through incremental evaluation. Moreover, it gives students an opportunity to increase their understanding of genome biology and to participate in scientific research in collaboration with peers and senior researchers at multiple institutions

Is healthy neuroticism associated with health behaviors? A coordinated integrative data analysis

Current literature suggests that neuroticism is positively associated with maladaptive life choices, likelihood of disease, and mortality. However, recent research has identified circumstances under which neuroticism is associated with positive outcomes. The current project examined whether “healthy neuroticism”, defined as the interaction of neuroticism and conscientiousness, was associated with the following health behaviors: smoking, alcohol consumption, and physical activity. Using a pre-registered multi-study coordinated integrative data analysis (IDA) approach, we investigated whether “healthy neuroticism” predicted the odds of engaging in each of the aforementioned activities. Each study estimated identical models, using the same covariates and data transformations, enabling optimal comparability of results. These results were then meta-analyzed in order to estimate an average (N-weighted) effect and to ascertain the extent of heterogeneity in the effects. Overall, these results suggest that neuroticism alone was not related to health behaviors, while individuals higher in conscientiousness were less likely to be smokers or drinkers, and more likely to engage in physical activity. In terms of the healthy neuroticism interaction of neuroticism and conscientiousness, significant interactions for smoking and physical activity suggest that the association between neuroticism and health behaviors was smaller among those high in conscientiousness. These findings lend credence to the idea that healthy neuroticism may be linked to certain health behaviors and that these effects are generalizable across several heterogeneous samples

Is healthy neuroticism associated with longevity? A coordinated integrative data analysis

Early investigations of the neuroticism by conscientiousness interaction with regards to health have been promising, but to date, there have been no systematic investigations of this interaction that account for the various personality measurement instruments, varying populations, or aspects of health. The current study - the second of three - uses a coordinated analysis approach to test the impact of the neuroticism by conscientiousness interaction on the prevalence and incidence of chronic conditions. Using 15 pre-existing longitudinal studies (N > 49,375), we found that conscientiousness did not moderate the relationship between neuroticism and having hypertension (OR = 1.00,95%CI[0.98,1.02]), diabetes (OR = 1.02[0.99,1.04]), or heart disease (OR = 0.99[0.97,1.01]). Similarly, we found that conscientiousness did not moderate the prospective relationship between neuroticism and onset of hypertension (OR = 0.98,[0.95,1.01]), diabetes (OR = 0.99[0.94,1.05]), or heart disease (OR = 0.98[0.94,1.03]). Heterogeneity of effect sizes was largely nonsignificant, with one exception, indicating that the effects are consistent between datasets. Overall, we conclude that there is no evidence that healthy neuroticism, operationalized as the conscientiousness by neuroticism interaction, buffers against chronic conditions

Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy

Corticobasal degeneration (CBD) is a neurodegenerative disorder affecting movement and cognition, definitively diagnosed only at autopsy. Here, we conduct a genome-wide association study (GWAS) in CBD cases (n = 152) and 3, 311 controls, and 67 CBD cases and 439 controls in a replication stage. Associations with meta-analysis were 17q21 at MAPT (P = 1.42 x 10(-12)),8p12 at lnc-KIF13B-1, a long non-coding RNA (rs643472;P = 3.41 x 10(-8)),and 2p22 at SOS1 (rs963731;P = 1.76 x 10(-7)). Testing for association of CBD with top progressive supranuclear palsy (PSP) GWAS single-nucleotide polymorphisms (SNPs) identified associations at MOBP (3p22;rs1768208;P = 2.07 x 10(-7)) and MAPT H1c (17q21;rs242557;P = 7.91 x 10(-6)). We previously reported SNP/transcript level associations with rs8070723/MAPT, rs242557/MAPT, and rs1768208/MOBP and herein identified association with rs963731/SOS1. We identify new CBD susceptibility loci and show that CBD and PSP share a genetic risk factor other than MAPT at 3p22 MOBP (myelin-associated oligodendrocyte basic protein)

HLA Genes, Islet Autoantibodies and Residual C-Peptide at the Clinical Onset of Type 1 Diabetes Mellitus and the Risk of Retinopathy 15 Years Later

HLA genes, islet autoantibodies and residual C-peptide were studied to determine the independent association of each exposure with diabetic retinopathy (DR), 15 years after the clinical onset of type 1 diabetes in 15-34 year old individuals.The cohort was identified in 1992 and 1993 by the Diabetes Incidence Study in Sweden (DISS), which investigates incident cases of diabetes for patients between 15 and 34 years of age. Blood samples at diagnosis were analyzed to determine HLA genotype, islet autoantibodies and serum C-peptide. In 2009, fundus photographs were obtained from patient records. Study measures were supplemented with data from the Swedish National Diabetes Registry.The prevalence of DR was 60.2% (148/246). Autoantibodies against the 65 kD isoform of glutamate decarboxylase (GADA) at the onset of clinical diabetes increased the risk of DR 15 years later, relative risk 1.12 for each 100 WHO units/ml, [95% CI 1.02 to 1.23]. This equates to risk estimates of 1.27, [95% CI 1.04 to 1.62] and 1.43, [95% CI 1.06 to 1.94] for participants in the highest 25(th) (GADA>233 WHO units/ml) and 5(th) percentile (GADA>319 WHO units/ml) of GADA, respectively. These were adjusted for duration of diabetes, HbA(1c), treated hypertension, sex, age at diagnosis, HLA and C-peptide. Islet cell autoantibodies, insulinoma-antigen 2 autoantibodies, residual C-peptide and the type 1 diabetes associated haplotypes DQ2, DQ8 and DQ6 were not associated with DR.Increased levels of GADA at the onset of type 1 diabetes were associated with DR 15 years later. These results, if confirmed, could provide additional insights into the pathogenesis of the most common microvascular complication of diabetes and lead to better risk stratification for both patient screenings and DR treatment trials

From protein sequences to 3D-structures and beyond: the example of the UniProt Knowledgebase

With the dramatic increase in the volume of experimental results in every domain of life sciences, assembling pertinent data and combining information from different fields has become a challenge. Information is dispersed over numerous specialized databases and is presented in many different formats. Rapid access to experiment-based information about well-characterized proteins helps predict the function of uncharacterized proteins identified by large-scale sequencing. In this context, universal knowledgebases play essential roles in providing access to data from complementary types of experiments and serving as hubs with cross-references to many specialized databases. This review outlines how the value of experimental data is optimized by combining high-quality protein sequences with complementary experimental results, including information derived from protein 3D-structures, using as an example the UniProt knowledgebase (UniProtKB) and the tools and links provided on its website (http://www.uniprot.org/). It also evokes precautions that are necessary for successful predictions and extrapolations

Description of the Baseline Audiologic Characteristics of the Participants Enrolled in the Aging and Cognitive Health Evaluation in Elders Study

Purpose:The Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study is a randomized clinical trial designed to determine the effects of a best-practice hearing intervention versus a successful aging health education control intervention on cognitive decline among community-dwelling older adults with untreated mild-to-moderate hearing loss. We describe the baseline audiologic characteristics of the ACHIEVE participants.Method:Participants aged 70–84 years (N = 977; Mage = 76.8) were enrolled at four U.S. sites through two recruitment routes: (a) an ongoing longitudinal study and (b) de novo through the community. Participants underwent diagnostic evaluation including otoscopy, tympanometry, pure-tone and speech audiometry, speech-in-noise testing, and provided self-reported hearing abilities. Baseline characteristics are reported as frequencies (percentages) for categorical variables or medians (interquartiles, Q1–Q3) for continuous variables. Between-groups comparisons were conducted using chi-square tests for categorical variables or Kruskal–Wallis test for continuous variables. Spearman correlations assessed relationships between measured hearing function and self-reported hearing handicap.Results:The median four-frequency pure-tone average of the better ear was 39 dB HL, and the median speech-in-noise performance was a 6-dB SNR loss, indicating mild speech-in-noise difficulty. No clinically meaningful differences were found across sites. Significant differences in subjective measures were found for recruitment route. Expected correlations between hearing measurements and self-reported handicap were found.Conclusions:The extensive baseline audiologic characteristics reported here will inform future analyses examining associations between hearing loss and cognitive decline. The final ACHIEVE data set will be publicly available for use among the scientific community

Socio-sexuality and episodic memory function in women: further evidence of an adaptive “mating mode”

The functionalist memory perspective predicts that information of adaptive value may trigger specific processing modes. It was recently demonstrated that women's memory is sensitive to cues of male sexual dimorphism (i.e., masculinity) that convey information of adaptive value for mate choice because they signal health and genetic quality, as well as personality traits important in relationship contexts. Here, we show that individual differences in women's mating strategies predict the effect of facial masculinity cues upon memory, strengthening the case for functional design within memory. Using the revised socio-sexual orientation inventory, Experiment 1 demonstrates that women pursuing a short-term, uncommitted mating strategy have enhanced source memory for men with exaggerated versus reduced masculine facial features, an effect that reverses in women who favor long-term committed relationships. The reversal in the direction of the effect indicates that it does not reflect the sex typicality of male faces per se. The same pattern occurred within women's source memory for women's faces, implying that the memory bias does not reflect the perceived attractiveness of faces per se. In Experiment 2, we reran the experiment using men's faces to establish the reliability of the core finding and replicated Experiment 1's results. Masculinity cues may therefore trigger a specific mode within women's episodic memory. We discuss why this mode may be triggered by female faces and its possible role in mate choice. In so doing, we draw upon the encoding specificity principle and the idea that episodic memory limits the scope of stereotypical inferences about male behavior

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder