Genome-Scale Analysis of Translation Elongation with a Ribosome Flow Model

We describe the first large scale analysis of gene translation that is based on a model that takes into account the physical and dynamical nature of this process. The Ribosomal Flow Model (RFM) predicts fundamental features of the translation process, including translation rates, protein abundance levels, ribosomal densities and the relation between all these variables, better than alternative (‘non-physical’) approaches. In addition, we show that the RFM can be used for accurate inference of various other quantities including genes' initiation rates and translation costs. These quantities could not be inferred by previous predictors. We find that increasing the number of available ribosomes (or equivalently the initiation rate) increases the genomic translation rate and the mean ribosome density only up to a certain point, beyond which both saturate. Strikingly, assuming that the translation system is tuned to work at the pre-saturation point maximizes the predictive power of the model with respect to experimental data. This result suggests that in all organisms that were analyzed (from bacteria to Human), the global initiation rate is optimized to attain the pre-saturation point. The fact that similar results were not observed for heterologous genes indicates that this feature is under selection. Remarkably, the gap between the performance of the RFM and alternative predictors is strikingly large in the case of heterologous genes, testifying to the model's promising biotechnological value in predicting the abundance of heterologous proteins before expressing them in the desired host

Non-invasive Approaches for the Diagnosis of Autoimmune/Autoinflammatory Skin Diseases—A Focus on Psoriasis and Lupus erythematosus

The traditional diagnostic gold standard for inflammatory skin lesions of unclear etiology is dermato-histopathology. As this approach requires an invasive skin biopsy, biopsy processing and analysis by specialized histologists, it is a resource intensive approach requiring trained healthcare professionals. In many health care settings access to this diagnostic approach can be difficult and outside emergency cases will usually take several weeks. This scenario leads to delayed or inappropriate treatment given to patients. With dramatically increased sensitivity of a range of analysis systems including mass spectrometry, high sensitivity, multiplex ELISA based systems and PCR approaches we are now able to “measure” samples with unprecedented sensitivity and accuracy. Other important developments include the long-term monitoring of parameters using microneedle approaches and the improvement in imaging systems such as optical coherence tomography. In this review we will focus on recent achievements regarding measurements from non-invasive sampling, in particular from plucked hair and skin tape-strips which seem well suited for the diagnosis of lupus erythematosus and psoriatic inflammation, respectively. While these approaches will not replace clinical observation—they can contribute to improved subgroup diagnosis, stratified therapeutic approaches and have great potential for providing molecular and mechanistic insight in to inflammatory skin diseases.With dramatically increased sensitivity of a range of analysis systems including mass spectrometry, high sensitivity, multiplex ELISA based systems and PCR approaches we are now able to “measure” samples with unprecedented sensitivity and accuracy. Other important developments include the long-term monitoring of parameters using microneedle approaches and the improvement in imaging systems such as optical coherence tomography. In this review we will focus on recent achievements regarding measurements from non-invasive sampling, in particular from plucked hair and skin tape-strips which seem well suited for the diagnosis of lupus erythematosus and psoriatic inflammation, respectively. While these approaches will not replace clinical observation – they can contribute to improved subgroup diagnosis, stratified therapeutic approaches and have great potential for providing molecular and mechanistic insight in to inflammatory skin disease