Single-nucleotide polymorphisms (SNPs) are the most frequent type of variation in the human genome, and they provide powerful tools for a variety of medical genetic studies. In a large-scale survey for SNPs, 2.3 megabases of human genomic DNA was examined by a combination of gel-based sequencing and high-density variation-detection DNA chips. A total of 3241 candidate SNPs were identified. A genetic map was constructed showing the location of 2227 of these SNPs. Prototype genotyping chips were developed that allow simultaneous genotyping of 500 SNPs. The results provide a characterization of human diversity at the nucleotide level and demonstrate the feasibility of large-scale identification of human SNPs.
Mapping protein-protein interactions is an invaluable tool for understanding protein function. Here, we report the first large-scale study of protein-protein interactions in human cells using a mass spectrometry-based approach. The study maps protein interactions for 338 bait proteins that were selected based on known or suspected disease and functional associations. Large-scale immunoprecipitation of Flag-tagged versions of these proteins followed by LC-ESI-MS/MS analysis resulted in the identification of 24 540 potential protein interactions. False positives and redundant hits were filtered out using empirical criteria and a calculated interaction confidence score, producing a data set of 6463 interactions between 2235 distinct proteins. This data set was further cross-validated using previously published and predicted human protein interactions. In-depth mining of the data set shows that it represents a valuable source of novel protein-protein interactions with relevance to human diseases. In addition, via our preliminary analysis, we report many novel protein interactions and pathway associations.
Strategic reasoning about business models is an integral part of service design. In fast moving markets, businesses must be able to recognize and respond strategically to disruptive change. They have to answer questions such as: what are the threats and opportunities in emerging technologies and innovations? How should they target customer groups? Who are their real competitors? How will competitive battles take shape? In this paper we define a strategic modeling framework to help understand and analyze the goals, intentions, roles, and the rationale behind the strategic actions in a business environment. This understanding is necessary in order to improve existing or design new services. The key component of the framework is a strategic business model ontology for representing and analyzing business models and strategies, using the i* agent and goal oriented methodology as a basis. The ontology introduces a strategy layer which reasons about alternative strategies that are realized in the operational layer. The framework is evaluated using a retroactive example of disruptive technology in the telecommunication services sector from the literature.
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