We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.

BackgroundBacteriophage genomes have mosaic architectures and are replete with small open reading frames of unknown function, presenting challenges in their annotation, comparative analysis, and representation.ResultsWe describe here a bioinformatic tool, Phamerator, that assorts protein-coding genes into phamilies of related sequences using pairwise comparisons to generate a database of gene relationships. This database is used to generate genome maps of multiple phages that incorporate nucleotide and amino acid sequence relationships, as well as genes containing conserved domains. Phamerator also generates phamily circle representations of gene phamilies, facilitating analysis of the different evolutionary histories of individual genes that migrate through phage populations by horizontal genetic exchange.ConclusionsPhamerator represents a useful tool for comparative genomic analysis and comparative representations of bacteriophage genomes.

It has long been posited that human and other large genomes are organized into higher-order (i.e., greater than gene-sized) functional domains. We hypothesized that diverse experimental data types generated by The ENCODE Project Consortium could be combined to delineate active and quiescent or repressed functional domains and thereby illuminate the higher-order functional architecture of the genome. To address this, we coupled wavelet analysis with hidden Markov models for unbiased discovery of "domain-level" behavior in high-resolution functional genomic data, including activating and repressive histone modifications, RNA output, and DNA replication timing. We find that higher-order patterns in these data types are largely concordant and may be analyzed collectively in the context of HeLa cells to delineate 53 active and 62 repressed functional domains within the ENCODE regions. Active domains comprise ∼44% of the ENCODE regions but contain ∼75%-80% of annotated genes, transcripts, and CpG islands. Repressed domains are enriched in certain classes of repetitive elements and, surprisingly, in evolutionarily conserved nonexonic sequences. The functional domain structure of the ENCODE regions appears to be largely stable across different cell types. Taken together, our results suggest that higher-order functional domains represent a fundamental organizing principle of human genome architecture.

http://noble.gs.washington.edu/proj/hmmseg

Soft robots have the potential to transform the way robots interact with their environment. This is due to their low inertia and inherent ability to more safely interact with the world without damaging themselves or the people around them. However, existing sensing for soft robots has at least partially limited their ability to control interactions with their environment. Tactile sensors could enable soft robots to sense interaction, but most tactile sensors are made from rigid substrates and are not well suited to applications for soft robots which can deform. In addition, the benefit of being able to cheaply manufacture soft robots may be lost if the tactile sensors that cover them are expensive and their resolution does not scale well for manufacturability. This paper discusses the development of a method to make affordable, high-resolution, tactile sensor arrays (manufactured in rows and columns) that can be used for sensorizing soft robots and other soft bodies. However, the construction results in a sensor array that exhibits significant amounts of cross-talk when two taxels in the same row are compressed. Using the same fabric-based tactile sensor array construction design, two different methods for cross-talk compensation are presented. The first uses a mathematical model to calculate a change in resistance of each taxel directly. The second method introduces additional simple circuit components that enable us to isolate each taxel electrically and relate voltage to force directly. Fabric sensor arrays are demonstrated for two different soft-bodied applications: an inflatable single link robot and a human wrist.