SBV IMPROVER: The Species Translation Challenge

Inferring how humans respond to external cues such as drugs, chemicals, viruses or hormones is an essential question in biomedicine. Very often, however, this question cannot be addressed due to the impossibility to perform experiments in humans. A reasonable alternative consists of generating responses in animal models and “translating” the results to humans. The limitations of such translation, however, are far from clear, and systematic assessments of its actual potential are badly needed. We have designed a series of challenges in the context of the IMPROVER (Industrial Methodology for Process Verification in Research; http://sbvimprover.com/) project to address the issue of translatability between humans and rodents. Our main aim is to understand the limits and opportunities of species to species translatability at different levels of biological organization: Signaling, transcriptional, and release of secreted factors (such as cytokines, chemokines or growth factors). To address this question, we selected normal bronchial epithelial cells from both human and rat origin. These cells were exposed to 50 different substances and for each stimulus we collected phosphoproteomic, gene expression and protein measurement of secreted factors data. These data were collected at different time points, aligned with the associated biological processes such thati) Phosphoproteomic data was collected after 5 min and 25 min of exposure,ii) Gene expression data was collected after 6 hours of exposure andiii) Secreted factors release after 24 hours of exposure.Our challenge will provide participants with both training and test data sets which are designed to assess the ability of methods to predict the responses in normal human bronchial epithelial cells, from the responses observed in normal rat bronchial epithelial primary cells. The central questions that we will pose in this challenge are:Can the phosphoproteomic responses induced by stimuli addressing several distinct signaling pathways in human cells be predicted given the responses generated with the same stimuli in rat cells? How does the accuracy of the prediction depend on the nature of the applied perturbation? Which gene expression regulatory processes (biological pathways / functions) are translatable and therefore predictable across species, and which are too divergent?Summarizing, we will present the community with questions and data aimed at assessing methodologies designed to infer human biology from non-human biology.