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From Genome to Regulatory Networks For biologists, having a genome in hand is only the beginning—much more investigation is still needed to characterize how the genome is used to help to produce a functional organism (see the Perspective by Blaxter ). In this vein, Gerstein et al. (p. 1775 ) summarize for the Caenorhabditis elegans genome, and The modENCODE Consortium (p. 1787 ) summarize for the Drosophila melanogaster genome, full transcriptome analyses over developmental stages, genome-wide identification of transcription factor binding sites, and high-resolution maps of chromatin organization. Both studies identified regions of the nematode and fly genomes that show highly occupied targets (or HOT) regions where DNA was bound by more than 15 of the transcription factors analyzed and the expression of related genes were characterized. Overall, the studies provide insights into the organization, structure, and function of the two genomes and provide basic information needed to guide and correlate both focused and genome-wide studies.

That imaginative literature can be used as a data source for geographical analysis and understanding of place seems a reasonable (and potentially rewarding) possibility, based as it is on the premise that art mirrors life. However the mode in which — and the extent to which — literature reflects the society that engenders it must be addressed and clarified. Geographers seem principally to have engaged literature for its capacity to describe landscape and render a 'sense of place,' or to depict individual experience of place. These approaches assume that literature presents a simple, straightforward, representative reflection of either reality or the experience of reality and geographers have too often neglected to specify the links that they assume between literature and geography. Some writers have however suggested more comprehensive approaches to geographical analysis of literary data and others have theoretically addressed the issue of analogical representation in everyday life, in literature and in geographical analysis. This thesis is concerned with urban imagery as it can symbolically reveal the perceptual framework through which we order and understand our world. It examines the urban imagery that permeates our fiction and that can reveal how we fundamentally view our cities as living places. Thus the focus is on imagery and symbolic depiction, rather than realistic depiction of place or experience; with the application of an ordering framework rather than intuitive interpretation of literary data; with an explicit mode of analysis that defines the links it posits between art and society. It is fundamentally concerned with the perception of urban place as it is imaginatively rendered. A preliminary survey of Canadian urban novels of the past two decades revealed two points that became the nexus of this analysis. First, the image of the city is a remarkably consistent one — and it is remarkable as well for its negative emphasis. The city is overwhelmingly characterized as a menacing presence, a landscape defined by incoherence and disorder, provoking a sense of unease and vulnerability. Second, it became apparent that a framework would be necessary to organize and systematize the urban imagery, to reveal pattern in the amorphous mass of data, and to achieve more than a mere listing or cataloging of images. Further, a definition of the relationship between art and its social context must precede and guide any probing of literature for data. The concept of garrison mentality, borrowed from Northrop Frye and the field of literary criticism, provided the basis from which to develop such a framework. The linked themes of garrison and wilderness proved a comprehensive schema within which to analyze image and reaction in the urban novels. The image of city as wilderness that pervades these works is summarized and is illustrated by examples from urban anthologies; the three types of garrison provoked by this threatening fictive environment are detailed with reference to representative novels. The literary material, organized in this way, strongly suggests themes current in the work of various urban and social theorists. Such parallels serve to substantiate the hypothesis that image and reaction in fiction correlate closely with perception and behaviour in the everyday world. This suggests that literary symbolism is a valid way to explore our elemental modes of perception and frames of reference. It also raises further questions of the role of the interpreter — creative writer or social scientist— in promulgating a perspective, and of why a particular society gives rise to a particular vision of itself.

Regulatory proteins can bind to different sets of genomic targets in various cell types or conditions. To reliably characterize such condition-specific regulatory binding we introduce MultiGPS, an integrated machine learning approach for the analysis of multiple related ChIP-seq experiments. MultiGPS is based on a generalized Expectation Maximization framework that shares information across multiple experiments for binding event discovery. We demonstrate that our framework enables the simultaneous modeling of sparse condition-specific binding changes, sequence dependence, and replicate-specific noise sources. MultiGPS encourages consistency in reported binding event locations across multiple-condition ChIP-seq datasets and provides accurate estimation of ChIP enrichment levels at each event. MultiGPS's multi-experiment modeling approach thus provides a reliable platform for detecting differential binding enrichment across experimental conditions. We demonstrate the advantages of MultiGPS with an analysis of Cdx2 binding in three distinct developmental contexts. By accurately characterizing condition-specific Cdx2 binding, MultiGPS enables novel insight into the mechanistic basis of Cdx2 site selectivity. Specifically, the condition-specific Cdx2 sites characterized by MultiGPS are highly associated with pre-existing genomic context, suggesting that such sites are pre-determined by cell-specific regulatory architecture. However, MultiGPS-defined condition-independent sites are not predicted by pre-existing regulatory signals, suggesting that Cdx2 can bind to a subset of locations regardless of genomic environment. A summary of this paper appears in the proceedings of the RECOMB 2014 conference, April 2–5.