Expansive linguistic representations to predict interpretable odor mixture discriminability.

Language is often thought as being poorly adapted to precisely describe or quantify smell and olfactory attributes. In this work, we show that semantic descriptors of odors can be implemented in a model to successfully predict odor mixture discriminability, an olfactory attribute. We achieved this by taking advantage of the structure-to-percept model we previously developed for monomolecular odorants, using chemical descriptors to predict pleasantness, intensity and 19 semantic descriptors such as "fish," "cold," "burnt," "garlic," "grass," and "sweet" for odor mixtures, followed by a metric learning to obtain odor mixture discriminability. Through this expansion of the representation of olfactory mixtures, our Semantic model outperforms state of the art methods by taking advantage of the intermediary semantic representations learned from human perception data to enhance and generalize the odor discriminability/similarity predictions. As 10 of the semantic descriptors were selected to predict discriminability/similarity, our approach meets the need of rapidly obtaining interpretable attributes of odor mixtures as illustrated by the difficulty of finding olfactory metamers. More fundamentally, it also shows that language can be used to establish a metric of discriminability in the everyday olfactory space.

Fusion of biomedical imaging studies for increased sample size and diversity: a case study of brain MRI.

Data collection, curation, and cleaning constitute a crucial phase in Machine Learning (ML) projects. In biomedical ML, it is often desirable to leverage multiple datasets to increase sample size and diversity, but this poses unique challenges, which arise from heterogeneity in study design, data descriptors, file system organization, and metadata. In this study, we present an approach to the integration of multiple brain MRI datasets with a focus on homogenization of their organization and preprocessing for ML. We use our own fusion example (approximately 84,000 images from 54,000 subjects, 12 studies, and 88 individual scanners) to illustrate and discuss the issues faced by study fusion efforts, and we examine key decisions necessary during dataset homogenization, presenting in detail a database structure flexible enough to accommodate multiple observational MRI datasets. We believe our approach can provide a basis for future similarly-minded biomedical ML projects.

Atomist or holist? A diagnosis and vision for more productive interdisciplinary AI ethics dialogue.

In response to growing recognition of the social impacts of new artificial intelligence (AI)-based technologies, major AI and machine learning (ML) conferences and journals now encourage or require papers to include ethics impact statements and undergo ethics reviews. This move has sparked heated debate concerning the role of ethics in AI research, at times devolving into name calling and threats of "cancellation." We diagnose this conflict as one between "atomist" and "holist" ideologies. Among other things, atomists believe facts are and should be kept separate from values, while holists believe facts and values are and should be inextricable from one another. With the goal of reducing disciplinary polarization, we draw on numerous philosophical and historical sources to describe each ideology's core beliefs and assumptions. Finally, we call on atomists and holists within the ever-expanding data science community to exhibit greater empathy during ethical disagreements and propose four targeted strategies to ensure AI research benefits society.

Accurate clinical toxicity prediction using multi-task deep neural nets and contrastive molecular explanations.

Explainable machine learning for molecular toxicity prediction is a promising approach for efficient drug development and chemical safety. A predictive ML model of toxicity can reduce experimental cost and time while mitigating ethical concerns by significantly reducing animal and clinical testing. Herein, we use a deep learning framework for simultaneously modeling in vitro, in vivo, and clinical toxicity data. Two different molecular input representations are used; Morgan fingerprints and pre-trained SMILES embeddings. A multi-task deep learning model accurately predicts toxicity for all endpoints, including clinical, as indicated by the area under the Receiver Operator Characteristic curve and balanced accuracy. In particular, pre-trained molecular SMILES embeddings as input to the multi-task model improved clinical toxicity predictions compared to existing models in MoleculeNet benchmark. Additionally, our multitask approach is comprehensive in the sense that it is comparable to state-of-the-art approaches for specific endpoints in in vitro, in vivo and clinical platforms. Through both the multi-task model and transfer learning, we were able to indicate the minimal need of in vivo data for clinical toxicity predictions. To provide confidence and explain the model's predictions, we adapt a post-hoc contrastive explanation method that returns pertinent positive and negative features, which correspond well to known mutagenic and reactive toxicophores, such as unsubstituted bonded heteroatoms, aromatic amines, and Michael receptors. Furthermore, toxicophore recovery by pertinent feature analysis captures more of the in vitro (53%) and in vivo (56%), rather than of the clinical (8%), endpoints, and indeed uncovers a preference in known toxicophore data towards in vitro and in vivo experimental data. To our knowledge, this is the first contrastive explanation, using both present and absent substructures, for predictions of clinical and in vivo molecular toxicity.

Human-centered explainability for life sciences, healthcare, and medical informatics.

Rapid advances in artificial intelligence (AI) and availability of biological, medical, and healthcare data have enabled the development of a wide variety of models. Significant success has been achieved in a wide range of fields, such as genomics, protein folding, disease diagnosis, imaging, and clinical tasks. Although widely used, the inherent opacity of deep AI models has brought criticism from the research field and little adoption in clinical practice. Concurrently, there has been a significant amount of research focused on making such methods more interpretable, reviewed here, but inherent critiques of such explainability in AI (XAI), its requirements, and concerns with fairness/robustness have hampered their real-world adoption. We here discuss how user-driven XAI can be made more useful for different healthcare stakeholders through the definition of three key personas-data scientists, clinical researchers, and clinicians-and present an overview of how different XAI approaches can address their needs. For illustration, we also walk through several research and clinical examples that take advantage of XAI open-source tools, including those that help enhance the explanation of the results through visualization. This perspective thus aims to provide a guidance tool for developing explainability solutions for healthcare by empowering both subject matter experts, providing them with a survey of available tools, and explainability developers, by providing examples of how such methods can influence in practice adoption of solutions.

Predicting natural language descriptions of mono-molecular odorants.

There has been recent progress in predicting whether common verbal descriptors such as "fishy", "floral" or "fruity" apply to the smell of odorous molecules. However, accurate predictions have been achieved only for a small number of descriptors. Here, we show that applying natural-language semantic representations on a small set of general olfactory perceptual descriptors allows for the accurate inference of perceptual ratings for mono-molecular odorants over a large and potentially arbitrary set of descriptors. This is noteworthy given that the prevailing view is that humans' capacity to identify or characterize odors by name is poor. We successfully apply our semantics-based approach to predict perceptual ratings with an accuracy higher than 0.5 for up to 70 olfactory perceptual descriptors, a ten-fold increase in the number of descriptors from previous attempts. These results imply that the semantic distance between descriptors defines the equivalent of an odorwheel.

Predicting human olfactory perception from chemical features of odor molecules.

It is still not possible to predict whether a given molecule will have a perceived odor or what olfactory percept it will produce. We therefore organized the crowd-sourced DREAM Olfaction Prediction Challenge. Using a large olfactory psychophysical data set, teams developed machine-learning algorithms to predict sensory attributes of molecules based on their chemoinformatic features. The resulting models accurately predicted odor intensity and pleasantness and also successfully predicted 8 among 19 rated semantic descriptors ("garlic," "fish," "sweet," "fruit," "burnt," "spices," "flower," and "sour"). Regularized linear models performed nearly as well as random forest-based ones, with a predictive accuracy that closely approaches a key theoretical limit. These models help to predict the perceptual qualities of virtually any molecule with high accuracy and also reverse-engineer the smell of a molecule.