A user's guide to the Encyclopedia of DNA elements (ENCODE)

The mission of the Encyclopedia of DNA Elements (ENCODE) Project is to enable the scientific and medical communities to interpret the human genome sequence and apply it to understand human biology and improve health. The ENCODE Consortium is integrating multiple technologies and approaches in a collective effort to discover and define the functional elements encoded in the human genome, including genes, transcripts, and transcriptional regulatory regions, together with their attendant chromatin states and DNA methylation patterns. In the process, standards to ensure high-quality data have been implemented, and novel algorithms have been developed to facilitate analysis. Data and derived results are made available through a freely accessible database. Here we provide an overview of the project and the resources it is generating and illustrate the application of ENCODE data to interpret the human genome

Mapping and Analysis of Chromatin State Dynamics in Nine Human Cell Types

Chromatin profiling has emerged as a powerful means of genome annotation and detection of regulatory activity. The approach is especially well suited to the characterization of non-coding portions of the genome, which critically contribute to cellular phenotypes yet remain largely uncharted. Here we map nine chromatin marks across nine cell types to systematically characterize regulatory elements, their cell-type specificities and their functional interactions. Focusing on cell-type-specific patterns of promoters and enhancers, we define multicell activity profiles for chromatin state, gene expression, regulatory motif enrichment and regulator expression. We use correlations between these profiles to link enhancers to putative target genes, and predict the cell-type-specific activators and repressors that modulate them. The resulting annotations and regulatory predictions have implications for the interpretation of genome-wide association studies. Top-scoring disease single nucleotide polymorphisms are frequently positioned within enhancer elements specifically active in relevant cell types, and in some cases affect a motif instance for a predicted regulator, thus suggesting a mechanism for the association. Our study presents a general framework for deciphering cis-regulatory connections and their roles in disease.National Human Genome Research Institute (U.S.) (R01HG004037)National Human Genome Research Institute (U.S.) (RC1HG005334)National Science Foundation (U.S.). (Award 0644282)National Science Foundation (U.S.). (Award 0905968)Alfred P. Sloan Foundatio

The neural signature of empathy for physical pain...not quite there yet!

The perception and evaluation of other’s pain has been largely used in social neuroscience as a paradigm to study human empathy. Thanks to the growing attention given to this concept over the last 15 years, the cerebral bases of empathy in the context of physical pain are increasingly well documented. The aim of this chapter is to provide a critical overview of the most recent evidence while fostering discussion about the extent to which the cerebral changes associated with empathy can lead to a specific signature of this key process of social interactions. The authors firstly clarify the complex definition of empathy and its principal components, and make a clear distinction between pain perception in others, empathy and the behavioral outputs that can follow. Secondly, the cerebral networks underlying the distinct, yet interacting, components of empathy for physical pain are defined. Lastly, recent work on the factors that are likely to modulate empathy and these cerebral networks is discussed. The study of brain function has advanced our understanding of empathy in the context of physical pain considerably, but the complexity of this often fleeting process, especially in healthcare, is such that multiple levels of analysis will be needed to fully uncover its mysteries