A principal odor map unifies diverse tasks in olfactory perception.

Mapping molecular structure to odor perception is a key challenge in olfaction. We used graph neural networks to generate a principal odor map (POM) that preserves perceptual relationships and enables odor quality prediction for previously uncharacterized odorants. The model was as reliable as a human in describing odor quality: On a prospective validation set of 400 out-of-sample odorants, the model-generated odor profile more closely matched the trained panel mean than did the median panelist. By applying simple, interpretable, theoretically rooted transformations, the POM outperformed chemoinformatic models on several other odor prediction tasks, indicating that the POM successfully encoded a generalized map of structure-odor relationships. This approach broadly enables odor prediction and paves the way toward digitizing odors.

Metabolic activity organizes olfactory representations.

Hearing and vision sensory systems are tuned to the natural statistics of acoustic and electromagnetic energy on earth and are evolved to be sensitive in ethologically relevant ranges. But what are the natural statistics of odors, and how do olfactory systems exploit them? Dissecting an accurate machine learning model (Lee et al., 2022) for human odor perception, we find a computable representation for odor at the molecular level that can predict the odor-evoked receptor, neural, and behavioral responses of nearly all terrestrial organisms studied in olfactory neuroscience. Using this olfactory representation (principal odor map [POM]), we find that odorous compounds with similar POM representations are more likely to co-occur within a substance and be metabolically closely related; metabolic reaction sequences (Caspi et al., 2014) also follow smooth paths in POM despite large jumps in molecular structure. Just as the brain's visual representations have evolved around the natural statistics of light and shapes, the natural statistics of metabolism appear to shape the brain's representation of the olfactory world.