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DNA methylation as a predictor of fetal alcohol spectrum disorder

Background Fetal alcohol spectrum disorder (FASD) is a developmental disorder that manifests through a range of cognitive, adaptive, physiological, and neurobiological deficits resulting from prenatal alcohol exposure. Although the North American prevalence is currently estimated at 2–5%, FASD has proven difficult to identify in the absence of the overt physical features...

Profiling placental and fetal DNA methylation in human neural tube defects

Background The incidence of neural tube defects (NTDs) declined by about 40 % in Canada with the introduction of a national folic acid (FA) fortification program. Despite the fact that few Canadians currently exhibit folate deficiency, NTDs are still the second most common congenital abnormality. FA fortification may have aided in reducing the incidence of NTDs by overcoming...

Characterizing the state of the art in the computational assignment of gene function: lessons from the first critical assessment of functional annotation (CAFA)

Jesse Gillis Paul Pavlidis 0 0 Centre for High-Throughput Biology and Department of Psychiatry, University of British Columbia , 177 Michael Smith Laboratories 2185 East Mall, Vancouver , Canada

Assessing identity, redundancy and confounds in Gene Ontology annotations over time

Jesse Gillis 1 Paul Pavlidis 0 Associate Editor: Martin Bishop 0 Centre for High-Throughput Biology and Department of Psychiatry, University of British Columbia, 177 Michael Smith Laboratories , 2185

Meta-analysis of human methylomes reveals stably methylated sequences surrounding CpG islands associated with high gene expression

Background DNA methylation is thought to play an important role in the regulation of mammalian gene expression, partly based on the observation that a lack of CpG island methylation in gene promoters is associated with high transcriptional activity. However, the CpG island methylation level only accounts for a fraction of the variance in gene expression, and methylation in other...

“Guilt by Association” Is the Exception Rather Than the Rule in Gene Networks

Gene networks are commonly interpreted as encoding functional information in their connections. An extensively validated principle called guilt by association states that genes which are associated or interacting are more likely to share function. Guilt by association provides the central top-down principle for analyzing gene networks in functional terms or assessing their...

Meta-analysis of gene coexpression networks in the post-mortem prefrontal cortex of patients with schizophrenia and unaffected controls

Background Gene expression profiling of the postmortem human brain is part of the effort to understand the neuropathological underpinnings of schizophrenia. Existing microarray studies have identified a large number of genes as candidates, but efforts to generate an integrated view of molecular and cellular changes underlying the illness are few. Here, we have applied a novel...

DNA methylation signature of human fetal alcohol spectrum disorder

Background Prenatal alcohol exposure is the leading preventable cause of behavioral and cognitive deficits, which may affect between 2 and 5 % of children in North America. While the underlying mechanisms of alcohol’s effects on development remain relatively unknown, emerging evidence implicates epigenetic mechanisms in mediating the range of symptoms observed in children with...

The role of indirect connections in gene networks in predicting function

Motivation: Gene networks have been used widely in gene function prediction algorithms, many based on complex extensions of the ‘guilt by association’ principle. We sought to provide a unified explanation for the performance of gene function prediction algorithms in exploiting network structure and thereby simplify future analysis. Results: We use co-expression networks to show...

Wikidata as a semantic framework for the Gene Wiki initiative

Open biological data are distributed over many resources making them challenging to integrate, to update and to disseminate quickly. Wikidata is a growing, open community database which can serve this purpose and also provides tight integration with Wikipedia. In order to improve the state of biological data, facilitate data management and dissemination, we imported all human and...

Proteome TopFIND 3.0 with TopFINDer and PathFINDer: database and analysis tools for the association of protein termini to pre- and post-translational events

The knowledgebase TopFIND is an analysis platform focussed on protein termini, their origin, modification and hence their role on protein structure and function. Here, we present a major update to TopFIND, version 3, which includes a 70% increase in the underlying data to now cover a 90 696 proteins, 165 044 N-termini, 130 182 C-termini, 14 382 cleavage sites and 33 209 substrate...

The Impact of Multifunctional Genes on "Guilt by Association" Analysis

Many previous studies have shown that by using variants of “guilt-by-association”, gene function predictions can be made with very high statistical confidence. In these studies, it is assumed that the “associations” in the data (e.g., protein interaction partners) of a gene are necessary in establishing “guilt”. In this paper we show that multifunctionality, rather than...

Relationships between Gene Expression and Brain Wiring in the Adult Rodent Brain

We studied the global relationship between gene expression and neuroanatomical connectivity in the adult rodent brain. We utilized a large data set of the rat brain “connectome” from the Brain Architecture Management System (942 brain regions and over 5000 connections) and used statistical approaches to relate the data to the gene expression signatures of 17,530 genes in 142...

A methodology for the analysis of differential coexpression across the human lifespan

Background Differential coexpression is a change in coexpression between genes that may reflect 'rewiring' of transcriptional networks. It has previously been hypothesized that such changes might be occurring over time in the lifespan of an organism. While both coexpression and differential expression of genes have been previously studied in life stage change or aging...

Network Analyses Reveal Pervasive Functional Regulation Between Proteases in the Human Protease Web

Network modeling of interactions between proteases and their inhibitors reveals a network of new protein connections and cascades in the protease web.

Gene Ontology term overlap as a measure of gene functional similarity

Background The availability of various high-throughput experimental and computational methods allows biologists to rapidly infer functional relationships between genes. It is often necessary to evaluate these predictions computationally, a task that requires a reference database for functional relatedness. One such reference is the Gene Ontology (GO). A number of groups have...

miRNA and miRNA target genes in copy number variations occurring in individuals with intellectual disability

Paul Pavlidis 2 Evica Rajcan-Separovic 1 0 Equal contributors 1 Department of Pathology and Lab Medicine, BC Child and Family Research Institute, University of British Columbia (UBC) , Vancouver, BC V5Z

Decoding Unattended Fearful Faces with Whole-Brain Correlations: An Approach to Identify Condition-Dependent Large-Scale Functional Connectivity

Processing of unattended threat-related stimuli, such as fearful faces, has been previously examined using group functional magnetic resonance (fMRI) approaches. However, the identification of features of brain activity containing sufficient information to decode, or “brain-read”, unattended (implicit) fear perception remains an active research goal. Here we test the hypothesis...

Informatics in neuroscience

Leon French Paul Pavlidis The application of informatics to neuroscience goes far beyond 'traditional' bioinformatics modalities such as DNA sequences. In this review, we describe how informatics