13 research outputs found

    The Arabidopsis Framework Model version 2 predicts the organism-level effects of circadian clock gene mis-regulation

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    Predicting a multicellular organism’s phenotype quantitatively from its genotype is challenging, as genetic effects must propagate across scales. Circadian clocks are intracellular regulators that control temporal gene expression patterns and hence metabolism, physiology and behaviour. Here we explain and predict canonical phenotypes of circadian timing in a multicellular, model organism. We used diverse metabolic and physiological data to combine and extend mathematical models of rhythmic gene expression, photoperiod-dependent flowering, elongation growth and starch metabolism within a Framework Model for the vegetative growth of Arabidopsis thaliana, sharing the model and data files in a structured, public resource. The calibrated model predicted the effect of altered circadian timing upon each particular phenotype in clock-mutant plants under standard laboratory conditions. Altered night-time metabolism of stored starch accounted for most of the decrease in whole-plant biomass, as previously proposed. Mobilisation of a secondary store of malate and fumarate was also mis-regulated, accounting for any remaining biomass defect. The three candidate mechanisms tested did not explain this organic acid accumulation. Our results link genotype through specific processes to higher-level phenotypes, formalising our understanding of a subtle, pleiotropic syndrome at the whole-organism level, and validating the systems approach to understand complex traits starting from intracellular circuits

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∌99% of the euchromatic genome and is accurate to an error rate of ∌1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    Cloud and Network facilities federation in BonFIRE

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    International audienceIn recent years we have seen how Cloud Computing is changing the way of doing businesses and how services are delivered over the Internet. This disruption is a major challenge for Service Providers and Independent Software Vendors when creating new services and software applications for the Cloud. BonFIRE offers a federated, multi-site cloud testbed to support large-scale testing of applications, services and systems. This is achieved by federating geographically distributed, heterogeneous clouds testbeds where each exposes unique configuration and/or features while giving to the experimenters (users) an homogeneous way to interact with the facility. All those testbeds are controlled by a central set of services commonly denominated “Broker”. Additionally, BonFIRE is federated with different network facilities like the Virtual Wall, FEDERICA and AutoBAHN to provide high-level interfaces to network control functionality, in order to simulate diverse network QoS scenarios, enabling vertical federatio
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