A System-Wide Understanding of the Human Olfactory Percept Chemical Space.

The fundamental units of olfactory perception are discrete 3D structures of volatile chemicals that each interact with specific subsets of a very large family of hundreds of odorant receptor proteins, in turn activating complex neural circuitry and posing a challenge to understand. We have applied computational approaches to analyze olfactory perceptual space from the perspective of odorant chemical features. We identify physicochemical features associated with ~150 different perceptual descriptors and develop machine-learning models. Validation of predictions shows a high success rate for test set chemicals within a study, as well as across studies more than 30 years apart in time. Due to the high success rates, we are able to map ~150 percepts onto a chemical space of nearly 0.5 million compounds, predicting numerous percept-structure combinations. The chemical structure-to-percept prediction provides a system-level view of human olfaction and opens the door for comprehensive computational discovery of fragrances and flavors.