BACKGROUND: Global run-on coupled with deep sequencing (GRO-seq) provides extensive information on the location and function of coding and non-coding transcripts, including primary microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and enhancer RNAs (eRNAs), as well as yet undiscovered classes of transcripts. However, few computational tools tailored toward this new type of sequencing data are available, limiting the applicability of GRO-seq data for identifying novel transcription units. RESULTS: Here, we present groHMM, a computational tool in R, which defines the boundaries of transcription units de novo using a two state hidden-Markov model (HMM). A systematic comparison of the performance between groHMM and two existing peak-calling methods tuned to identify broad regions (SICER and HOMER) favorably supports our approach on existing GRO-seq data from MCF-7 breast cancer cells. To demonstrate the broader utility of our approach, we have used groHMM to annotate a diverse array of transcription units (i.e., primary transcripts) from four GRO-seq data sets derived from cells representing a variety of different human tissue types, including non-transformed cells (cardiomyocytes and lung fibroblasts) and transformed cells (LNCaP and MCF-7 cancer cells), as well as non-mammalian cells (from flies and worms). As an example of the utility of groHMM and its application to questions about the transcriptome, we show how groHMM can be used to analyze cell type-specific enhancers as defined by newly annotated enhancer transcripts. CONCLUSIONS: Our results show that groHMM can reveal new insights into cell type-specific transcription by identifying novel transcription units, and serve as a complete and useful tool for evaluating functional genomic elements in cells.

At the conceptual level, business rules are formulated from an external observation perspective according to the event-condition-action structure of rules in active database systems. Situation/activation diagrams homogeneously extend object/behavior diagrams to a graphical notation for the conceptual design of business objects and their associated business rules. Situation diagrams provide a high-level representation of logical events. Activation diagrams specify graphically which activities have to be performed upon some triggering event if an associated condition is satisfied. The developed editor supports both object/behavior diagrams and situation/activation diagrams. The editor performs syntactic consistency checks during the interactive design process. Moreover, by building the logical model in parallel with the diagrams, the editor guarantees that local semantic consistency checks can be performed incrementally, too. The editor clearly separates between schema data and pure visualization data describing the location of diagram elements. This separation facilitates the reuse of the generated data for further processing. Both schema data and visualization data are stored in the commercial object-oriented database system GemStone. Alternatively, those data may be stored in a file. The editor has been implemented using VisualWorks and MetaDoME, a framework for building graphical editors with VisualWorks.