Martin Schindler

AthaMap: an online resource for in silico transcription factor binding sites in the Arabidopsis thaliana genome

Gene expression is controlled mainly by the binding of transcription factors to regulatory sequences. To generate a genomic map for regulatory sequences, the Arabidopsis thaliana genome was screened for putative transcription factor binding sites. Using publicly available data from the TRANSFAC database and from publications, alignment matrices for 23 transcription factors of 13 different factor families were used with the pattern search program Patser to determine the genomic positions of more than 2.4 x 10(6) putative binding sites. Due to the dense clustering of genes and the observation that regulatory sequences are not restricted to upstream regions, the prediction of binding sites was performed for the whole genome. The genomic positions and the underlying data were imported into the newly developed AthaMap database. This data can be accessed by positional information or the Arabidopsis Genome Initiative identification number. Putative binding sites are displayed in the defined region. Data on the matrices used and on the thresholds applied in these screens are given in the database. Considering the high density of sites it will be a valuable resource for generating models on gene expression regulation. The data are available at http://www.athamap.de.

AthaMap, integrating transcriptional and post-transcriptional data

The AthaMap database generates a map of predicted transcription factor binding sites (TFBS) for the whole Arabidopsis thaliana genome. AthaMap has now been extended to include data on post-transcriptional regulation. A total of 403 173 genomic positions of small RNAs have been mapped in the A. thaliana genome. These identify 5772 putative post-transcriptionally regulated target genes. AthaMap tools have been modified to improve the identification of common TFBS in co-regulated genes by subtracting post-transcriptionally regulated genes from such analyses. Furthermore, AthaMap was updated to the TAIR7 genome annotation, a graphic display of gene analysis results was implemented, and the TFBS data content was increased. AthaMap is freely available at http://www.athamap.de/.

An algebraic view on the semantics of model composition

Due to the increased complexity of software development projects more and more systems are described by models. The sheer size makes it impractical to describe these systems by a single model. Instead many models are developed that provide several complementary views on the system to be developed. This however leads to a need for compositional models. This paper describes a foundational theory of model composition in form of an algebra to explicitly clarify different variants and uses of composition, their interplay with the semantics of the involved models and their composition operators.

MontiCore: a framework for the development of textual domain specific languages

In this paper we demonstrate a framework for the efficient development of textual domain specific languages and supporting tools. We use a redundance-free and compact definition of a readable concrete syntax and a comprehensible abstract syntax as both representations significantly overlap in their structure. To further improve the usability of the abstract syntax, this definition format integrates additional concepts like associations and inheritance into the well-understood grammar-based approach. Modularity concepts like language inheritance and embedding are used to simplify the development of languages based on already existing ones. In addition, the generation of editors and a template approach for code generation is explained.

AthaMap web tools for database-assisted identification of combinatorial cis -regulatory elements and the display of highly conserved transcription factor binding sites in Arabidopsis thaliana

The AthaMap database generates a map of cis-regulatory elements for the Arabidopsis thaliana genome. AthaMap contains more than 7.4 × 106 putative binding sites for 36 transcription factors (TFs) from 16 different TF families. A newly implemented functionality allows the display of subsets of higher conserved transcription factor binding sites (TFBSs). Furthermore, a web tool was developed that permits a user-defined search for co-localizing cis-regulatory elements. The user can specify individually the level of conservation for each TFBS and a spacer range between them. This web tool was employed for the identification of co-localizing sites of known interacting TFs and TFs containing two DNA-binding domains. More than 1.8 × 105 combinatorial elements were annotated in the AthaMap database. These elements can also be used to identify more complex co-localizing elements consisting of up to four TFBSs. The AthaMap database and the connected web tools are a valuable resource for the analysis and the prediction of gene expression regulation at .

AthaMap web tools for the analysis and identification of co-regulated genes

The AthaMap database generates a map of cis-regulatory elements for the whole Arabidopsis thaliana genome. This database has been extended by new tools to identify common cis-regulatory elements in specific regions of user-provided gene sets. A resulting table displays all cis-regulatory elements annotated in AthaMap including positional information relative to the respective gene. Further tables show overviews with the number of individual transcription factor binding sites (TFBS) present and TFBS common to the whole set of genes. Over represented cis-elements are easily identified. These features were used to detect specific enrichment of drought-responsive elements in cold-induced genes. For identification of co-regulated genes, the output table of the colocalization function was extended to show the closest genes and their relative distances to the colocalizing TFBS. Gene sets determined by this function can be used for a co-regulation analysis in microarray gene expression databases such as Genevestigator or PathoPlant. Additional improvements of AthaMap include display of the gene structure in the sequence window and a significant data increase. AthaMap is freely available at .

PathoPlant: a platform for microarray expression data to analyze co-regulated genes involved in plant defense responses.

Plants react to pathogen attack by expressing specific proteins directed toward the infecting pathogens. This involves the transcriptional activation of specific gene sets. PathoPlant®, a database on plant–pathogen interactions and signal transduction reactions, has now been complemented by microarray gene expression data from Arabidopsis thaliana subjected to pathogen infection and elicitor treatment. New web tools enable identification of plant genes regulated by specific stimuli. Sets of genes co-regulated by multiple stimuli can be displayed as well. A user-friendly web interface was created for the submission of gene sets to be analyzed. This results in a table, listing the stimuli that act either inducing or repressing on the respective genes. The search can be restricted to certain induction factors to identify, e.g. strongly up- or down-regulated genes. Up to three stimuli can be combined with the option of induction factor restriction to determine similarly regulated genes. To identify common cis-regulatory elements in co-regulated genes, a resulting gene list can directly be exported to the AthaMap database for analysis. PathoPlant is freely accessible at .

A comparison of mechanisms for integrating handwritten and generated code for object-oriented programming languages

Code generation from models is a core activity in model-driven development (MDD). For complex systems it is usually impossible to generate the entire software system from models alone. Thus, MDD requires mechanisms for integrating generated and handwritten code. Applying such mechanisms without considering their effects can cause issues in projects with many model and code artifacts, where a sound integration for generated and handwritten code is necessary. We provide an overview of mechanisms for integrating generated and handwritten code for object-oriented languages. In addition to that, we define and apply criteria to compare these mechanisms. The results are intended to help MDD tool developers in choosing an appropriate integration mechanism.

Integration of Handwritten and Generated Object-Oriented Code

In many development projects models are core artifacts used to generate concrete implementations from them. However, for many systems it is impossible or not useful to generate the complete software system from models alone. Hence, developers need mechanisms for integrating generated and handwritten code. Applying such mechanisms without considering their effects can cause issues in projects, where model and code artifacts are essential. Thus, a sound approach for the integration of both forms of code is needed.

The 2013 State of the Journal report

Executive Summary:† 213 days from submission to final accept or reject. Thisshould be better.† As the backlog became too large, we do two things:SoSyM permanently increases the number of papers perissue from 192 to 224 pages (+32 pages) and we almostdouble(!)thenumberofpagesfor2014to448pages(issue1 and 2) and 304 pages (issue 3 and 4).† Impact factor SCI: 1.250 (previous: 1,061). This is anincrease of 17.8%.† New domains of modeling, like CPS, modeling big data,scientific models, or models of the world are not yetpresent enough.† In overall SoSyM is doing very well.SoSyM continues to experience an increasing number ofsubmissions. In 2013, 245 manuscripts were submitted, ofwhich67%werereviewedforregularissues,whiletheother33% were submitted for special or theme sections or indus-try voice. The average number of days from initial submis-sion to a final decision (that is, a final accept or reject) was213 days. It should be noted that this time includes the time