The video on the left shows an early report on systematical RNA-Seq biases (starting at time index 12:09) presented on the Genome Informatics conference 2009. Observation from these days became the basis of first models that formed the Flux Simulator.
The Flux Simulator aims at modeling RNA-Seq experiments in silico: sequencing reads are produced from a reference genome according annotated transcripts. The simulation pipeline models different steps as modules, each with a minimal set of parameters that can be estimated by experimental parameters. The first step is-in fact-a transcriptome simulator. Subsequently, common sources of systematic bias in the abundance and distribution of produced reads are simulated by in silico library preparation and sequencing.
Our models do not simulate molecular processes on the level of atoms, but represent a collection of deterministic approaches with a minimal set of parameters that can be estimated from observations of the experiment that is to be reproduced. Model development has to be understood as an iterative process to a maximal convergence of "model world" and "real world". It always requires a careful evaluation of all hypotheses and assumptions by comparison with experimental data.
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