Identification of biological mechanisms by semantic classifier systems

Abstract

The interpretability of a classification model is one of its most essential characteristics. It allows for the generation of new hypotheses on the molecular background of a disease. However, it is questionable if more complex molecular regulations can be reconstructed from such limited sets of data. To bridge the gap between complexity and interpretability, we replace the de novo reconstruction of these processes by a hybrid classification approach partially based on existing domain knowledge. Using semantic building blocks that reflect real biological processes these models were able to construct hypotheses on the underlying genetic configuration of the analysed phenotypes. As in the building process, also these hypotheses are composed of high-level biology-based terms. The semantic information we utilise from gene ontology is a vocabulary which comprises the essential processes or components of a biological system. The constructed semantic multi-classifier system consists of expert base classifiers which each select the most suitable term for characterising their assigned problems. Our experiments conducted on datasets of three distinct research fields revealed terms with well-known associations to the analysed context. Furthermore, some of the chosen terms do not seem to be obviously related to the issue and thus lead to new, hypotheses to pursue.\n\nAuthor summaryData mining strategies are designed for an unbiased de novo analysis of large sample collections and aim at the detection of frequent patterns or relationships. Later on, the gained information can be used to characterise diagnostically relevant classes and for providing hints to the underlying mechanisms which may cause a specific phenotype or disease. However, the practical use of data mining techniques can be restricted by the available resources and might not correctly reconstruct complex relationships such as signalling pathways.\n\nTo counteract this, we devised a semantic approach to the issue: a multi-classifier system which incorporates existing biological knowledge and returns interpretable models based on these high-level semantic terms. As a novel feature, these models also allow for qualitative analysis and hypothesis generation on the molecular processes and their relationships leading to different phenotypes or diseases.