Project description:For the purpose of the Gene Regulatory Network validation we have performed chromatin-immunoprecipitation sequencing (ChIP-Seq) experiment for three transcription factors; namely GATA3, MAF and MYB. ChIP-Seq of GATA3, MAF and MYB in human naïve CD4+ T-cells differentiated toward Th1 and Th2 until day 6. Matched INPUT samples were also sequenced for each condition.
Project description:For the purpose of the Gene Regulatory Network validation we have performed chromatin-immunoprecipitation sequencing (ChIP-Seq) experiment for three transcription factors; namely GATA3, MAF and MYB.
Project description:We present LASSIM, which is a toolbox built to build and infer parameters within mechanistic models on a genomic scale. This is made possible due to a property shared across biological systems, namely the existence of a subset of master regulators, here denoted the core system. The introduction of a core system of genes simplifies the inference into small solvable sub-problems, and implies that all main regulatory actions on peripheral genes come from a small set of regulator genes. This separation allows substantial parts of computations to be solved in parallel, i.e. permitting the use of a computer cluster, which substantially reduces the time for the computation to finish.
Project description:We present LASSIM, which is a toolbox built to build and infer parameters within mechanistic models on a genomic scale. This is made possible due to a property shared across biological systems, namely the existence of a subset of master regulators, here denoted the core system. The introduction of a core system of genes simplifies the inference into small solvable sub-problems, and implies that all main regulatory actions on peripheral genes come from a small set of regulator genes. This separation allows substantial parts of computations to be solved in parallel, i.e. permitting the use of a computer cluster, which substantially reduces the time for the computation to finish.
Project description:We present LASSIM, which is a toolbox built to build and infer parameters within mechanistic models on a genomic scale. This is made possible due to a property shared across biological systems, namely the existence of a subset of master regulators, here denoted the core system. The introduction of a core system of genes simplifies the inference into small solvable sub-problems, and implies that all main regulatory actions on peripheral genes come from a small set of regulator genes. This separation allows substantial parts of computations to be solved in parallel, i.e. permitting the use of a computer cluster, which substantially reduces the time for the computation to finish.
Project description:Recent and ongoing revolutions in measurement technologies imply completely new possibilities for genome research: today, time-resolved, quantitative, and systems-level data are available. Nevertheless, without a corresponding revolution in methods for data analysis, these new data tend to drown researchers and doctors, rather than provide clear and useful insights. Such new methods are developed within the field of systems biology. Systems biology has two main approaches: mechanistically detailed and well-determined simulation models for small subsystems, and more approximative statistical models for the entire genome. However, there are few, if any, methods that combine the strengths of these two approaches. Herein, we present LASSIM, a new simulation-based approach, which can be applied to systems of the size of the entire genome. The superior performance of LASSIM is demonstrated in three examples: i) an example with simulated data shows that unlike traditional large-scale methods, LASSIM correctly identifies the true behavior between measured data-points, ii) LASSIM outperforms the winner of a previous DREAM challenge, the most competitive benchmarking approach available, iii) based on new data from TH2 differentiation, LASSIM identifies a first mechanistic model for the entire genome. The key predictions of this model are typically enriched for DNA bindings, which suggests that most predicted interactions are direct. Moreover, in silico knockdowns were experimentally validated. In summary, LASSIM opens the door to a new type of model-based data analysis: to models that combine the strengths of reliable mechanistic models with truly systems-level data.
Project description:Recent and ongoing revolutions in measurement technologies imply completely new possibilities for genome research: today, time-resolved, quantitative, and systems-level data are available. Nevertheless, without a corresponding revolution in methods for data analysis, these new data tend to drown researchers and doctors, rather than provide clear and useful insights. Such new methods are developed within the field of systems biology. Systems biology has two main approaches: mechanistically detailed and well-determined simulation models for small subsystems, and more approximative statistical models for the entire genome. However, there are few, if any, methods that combine the strengths of these two approaches. Herein, we present LASSIM, a new simulation-based approach, which can be applied to systems of the size of the entire genome. The superior performance of LASSIM is demonstrated in three examples: i) an example with simulated data shows that unlike traditional large-scale methods, LASSIM correctly identifies the true behavior between measured data-points, ii) LASSIM outperforms the winner of a previous DREAM challenge, the most competitive benchmarking approach available, iii) based on new data from TH2 differentiation, LASSIM identifies a first mechanistic model for the entire genome. The key predictions of this model are typically enriched for DNA bindings, which suggests that most predicted interactions are direct. Moreover, in silico knockdowns were experimentally validated. In summary, LASSIM opens the door to a new type of model-based data analysis: to models that combine the strengths of reliable mechanistic models with truly systems-level data.