Exaggerated CpH methylation in the autism-affected brain.

BackgroundThe etiology of autism, a complex, heritable, neurodevelopmental disorder, remains largely unexplained. Given the unexplained risk and recent evidence supporting a role for epigenetic mechanisms in the development of autism, we explored the role of CpG and CpH (H = A, C, or T) methylation within the autism-affected cortical brain tissue.MethodsReduced representation bisulfite sequencing (RRBS) was completed, and analysis was carried out in 63 post-mortem cortical brain samples (Brodmann area 19) from 29 autism-affected and 34 control individuals. Analyses to identify single sites that were differentially methylated and to identify any global methylation alterations at either CpG or CpH sites throughout the genome were carried out.ResultsWe report that while no individual site or region of methylation was significantly associated with autism after multi-test correction, methylated CpH dinucleotides were markedly enriched in autism-affected brains (~2-fold enrichment at p < 0.05 cutoff, p = 0.002).ConclusionsThese results further implicate epigenetic alterations in pathobiological mechanisms that underlie autism

RNA-Seq optimization with eQTL gold standards.

BackgroundRNA-Sequencing (RNA-Seq) experiments have been optimized for library preparation, mapping, and gene expression estimation. These methods, however, have revealed weaknesses in the next stages of analysis of differential expression, with results sensitive to systematic sample stratification or, in more extreme cases, to outliers. Further, a method to assess normalization and adjustment measures imposed on the data is lacking.ResultsTo address these issues, we utilize previously published eQTLs as a novel gold standard at the center of a framework that integrates DNA genotypes and RNA-Seq data to optimize analysis and aid in the understanding of genetic variation and gene expression. After detecting sample contamination and sequencing outliers in RNA-Seq data, a set of previously published brain eQTLs was used to determine if sample outlier removal was appropriate. Improved replication of known eQTLs supported removal of these samples in downstream analyses. eQTL replication was further employed to assess normalization methods, covariate inclusion, and gene annotation. This method was validated in an independent RNA-Seq blood data set from the GTEx project and a tissue-appropriate set of eQTLs. eQTL replication in both data sets highlights the necessity of accounting for unknown covariates in RNA-Seq data analysis.ConclusionAs each RNA-Seq experiment is unique with its own experiment-specific limitations, we offer an easily-implementable method that uses the replication of known eQTLs to guide each step in one's data analysis pipeline. In the two data sets presented herein, we highlight not only the necessity of careful outlier detection but also the need to account for unknown covariates in RNA-Seq experiments

MULTI-OMIC DATA PROVIDE A MORE COMPLETE UNDERSTANDING OF THE AUTISTIC BRAIN

Autism is a complex neurodevelopmental disorder characterized by persistent social deficits and restricted or repetitive patterns of behavior. Despite an established genetic basis of the disorder, efforts to elucidate the genetic underpinnings of the disorder and our understanding of its etiology remains incomplete. As such, we set out to study the effects downstream of genetic variation by studying alterations in both gene expression and DNA methylation (DNAm) in post-mortem brain samples collected from individuals affected with autism and controls. This work highlights that even when there is no primary genetic lesion detected, the autistic brain shows a characteristic pattern of upregulation at M2-activation state microglia genes, a state potentially driven by Type I interferon responses. Additionally, by combining transcriptomic data across autism and two related neuropsychiatric disorders, schizophrenia and bipolar disorder, we have garnered a better understanding of the relationship between these disorders, where genes differentially expressed in autism are concordantly differentially expressed in schizophrenia, but not in bipolar disorder. Finally, as gene expression is regulated, at least in part, by DNAm, we have characterized DNAm at cytosines across the genome and have detected hypermethylation at cytosines outside the commonly-studied CpG context, suggesting that autistic brains have slight increases at many CpH sites (where H=A,T, or C) throughout their genome. These sites are enriched in repetitive regions of the genome and regions containing human-specific CpGs, offering an insight into how this hypermethylation may be functioning mechanistically. Taken together, by studying the downstream effects of genetic variation, at the levels of DNAm and gene expression, we have moved toward a more complete understanding of the autistic brain

Precision Agriculture: Yield Monitors (1998)

Yield monitors are an essential component of many site-specific management strategies. Yield maps, the visual and numerical product of yield monitors, encourage creative investigation and can provide reliable answers to carefully performed on-farm experiments. Yield maps provide feedback for determining the effects of managed inputs such as fertilizer and lime, seed and pesticides, and cultural practices such as tillage, irrigation and drainage

Landscape Features Affecting Northern Bobwhite Predator-Specific Nest Failures in Southeastern USA

Nest predation is a critical component in avian productivity and typically is the leading cause of nest failure for most birds. Several landscape features are thought to drive the behavioral interaction between northern bobwhite (Colinus virginianus; e.g., nest placement) and their predators (e.g., search methods for food acquisition). In order to understand habitat characteristics influencing predation, we studied bobwhite nests using 24-hour near-infrared video cameras. We monitored 675 bobwhite nests with cameras on 3 properties in northern Florida and southern Georgia, USA, during 2000–2006. To test the association between nest failures and specific failure causes with landscape structure, we calculated a suite of landscape metrics and examined these at 3 spatial scales (3.1 ha, 19.6 ha, and 50.3 ha). We found increased probability of nest success with greater proportions of, and proximity to, fallow and annually disked fields at larger scales (50.3 ha), but we found no landscape metrics to be important predictors of bobwhite nest failures at small scales (,20 ha). Fallow and disked fields may provide alternative prey items (e.g., rodents) important in buffering nest predation. Relative to meso-mammal predation, we observed increases in proportion of the landscape in field to be related to lower incidental nest failures at the smallest scale (3.1 ha). Nests closer to feed lines were more likely depredated by meso-mammals than ants at the 2 larger spatial scales. Interestingly, the fate of a nest was independent of the fate of neighboring nests, suggesting bobwhite nest predation may be primarily incidental

Further Examination of the Geographic Range of Eriogonum corymbosum var. nilesii (Polygonaceae, Eriogoneae)

The wild buckwheat Eriogonum corymbosum is widely distributed throughout the southwestern United States, forming a complex of eight varieties. E. corymbosum var. nilesii is a predominantly yellow-flowered variant reported primarily from Clark Co., Nevada. A previous genetic study by our research group found that var. nilesii is genetically distinct from other E. corymbosum varieties, based on a limited number of populations. Here, we assess genetic variation in 14 newly sampled yellow-flowered populations from southern Nevada, southern Utah, and northern Arizona, and compare them to genetic variation in six populations of previously determined E. corymbosum varieties. Of the new populations, we identified four as var. nilesii, four as var. aureum, three as var. glutinosum, two as apparent hybrids involving vars. aureum and nilesii, and one as a more distantly related admixture involving E. thompsoniae. Our results extend the range and area of E. corymbosum var. nilesii considerably from that traditionally stated in the literature. However, this extended range is confined to the Mojave Desert region of southern Nevada, and the number of known populations remains limited

Landscape Features Affecting Northern Bobwhite Predator-Specific Nest Failures in Southeastern USA

Nest predation is a critical component in avian productivity and typically is the leading cause of nest failure for most birds. Several landscape features are thought to drive the behavioral interaction between northern bobwhite (Colinus virginianus; e.g., nest placement) and their predators (e.g., search methods for food acquisition). In order to understand habitat characteristics influencing predation, we studied bobwhite nests using 24-hour near-infrared video cameras. We monitored 675 bobwhite nests with cameras on 3 properties in northern Florida and southern Georgia, USA, during 2000–2006. To test the association between nest failures and specific failure causes with landscape structure, we calculated a suite of landscape metrics and examined these at 3 spatial scales (3.1 ha, 19.6 ha, and 50.3 ha). We found increased probability of nest success with greater proportions of, and proximity to, fallow and annually disked fields at larger scales (50.3 ha), but we found no landscape metrics to be important predictors of bobwhite nest failures at small scales (\u3c20 \u3eha). Fallow and disked fields may provide alternative prey items (e.g., rodents) important in buffering nest predation. Relative to meso-mammal predation, we observed increases in proportion of the landscape in field to be related to lower incidental nest failures at the smallest scale (3.1 ha). Nests closer to feed lines were more likely depredated by meso-mammals than ants at the 2 larger spatial scales. Interestingly, the fate of a nest was independent of the fate of neighboring nests, suggesting bobwhite nest predation may be primarily incidental

Improving the value of public RNA-seq expression data by phenotype prediction.

Publicly available genomic data are a valuable resource for studying normal human variation and disease, but these data are often not well labeled or annotated. The lack of phenotype information for public genomic data severely limits their utility for addressing targeted biological questions. We develop an in silico phenotyping approach for predicting critical missing annotation directly from genomic measurements using well-annotated genomic and phenotypic data produced by consortia like TCGA and GTEx as training data. We apply in silico phenotyping to a set of 70 000 RNA-seq samples we recently processed on a common pipeline as part of the recount2 project. We use gene expression data to build and evaluate predictors for both biological phenotypes (sex, tissue, sample source) and experimental conditions (sequencing strategy). We demonstrate how these predictions can be used to study cross-sample properties of public genomic data, select genomic projects with specific characteristics, and perform downstream analyses using predicted phenotypes. The methods to perform phenotype prediction are available in the phenopredict R package and the predictions for recount2 are available from the recount R package. With data and phenotype information available for 70,000 human samples, expression data is available for use on a scale that was not previously feasible

Relative Entropy: Free Energy Associated with Equilibrium Fluctuations and Nonequilibrium Deviations

Using a one-dimensional macromolecule in aqueous solution as an illustration, we demonstrate that the relative entropy from information theory, $\sum_k p_k\ln(p_k/p_k^*)$, has a natural role in the energetics of equilibrium and nonequilibrium conformational fluctuations of the single molecule. It is identified as the free energy difference associated with a fluctuating density in equilibrium, and is associated with the distribution deviate from the equilibrium in nonequilibrium relaxation. This result can be generalized to any other isothermal macromolecular systems using the mathematical theories of large deviations and Markov processes, and at the same time provides the well-known mathematical results with an interesting physical interpretations.Comment: 5 page