Lauren Nicole DeLong

Lauren Nicole DeLong, Yojana Gadiya, Paola Galdi et al.

Background: Neurosymbolic (NeSy) artificial intelligence describes the combination of logic or rule-based techniques with neural networks. Compared to neural approaches, NeSy methods often possess enhanced interpretability, which is particularly promising for biomedical applications like drug discovery. However, no clear guidelines exist to assess the biological plausibility of model interpretations. Methods: To assess interpretability in the context of drug discovery, we devise a novel prediction task, called drug mechanism-of-action (MoA) deconvolution, with an associated, tailored knowledge graph (KG), MoA-net. We then develop the MoA Retrieval System (MARS), a NeSy approach for drug discovery which leverages logical rules with learned rule weights. Results: Using MARS' interpretable features alongside domain knowledge, we find that MARS and other NeSy approaches on KGs are susceptible to reasoning shortcuts, in which the prediction of true labels is driven by ``degree-bias'' rather than the domain-based rules. Subsequently, we demonstrate ways to identify and mitigate this. Thereafter, MARS achieves performance on par with current state-of-the-art models while producing model interpretations aligned with known MoAs. Conclusion: Through MARS, we showcase the novel task of computational MoA deconvolution. Our results emphasize the importance of using interpretable models, like NeSy ones, for applications in drug discovery. Specifically, by identifying and mitigating reasoning shortcuts, MARS MoA predictions which are biologically meaningful and, therefore, more reliable for downstream drug discovery research.

Lauren Nicole DeLong, Ramon Fernández Mir, Jacques D. Fleuriot

Neurosymbolic AI is an increasingly active area of research that combines symbolic reasoning methods with deep learning to leverage their complementary benefits. As knowledge graphs are becoming a popular way to represent heterogeneous and multi-relational data, methods for reasoning on graph structures have attempted to follow this neurosymbolic paradigm. Traditionally, such approaches have utilized either rule-based inference or generated representative numerical embeddings from which patterns could be extracted. However, several recent studies have attempted to bridge this dichotomy to generate models that facilitate interpretability, maintain competitive performance, and integrate expert knowledge. Therefore, we survey methods that perform neurosymbolic reasoning tasks on knowledge graphs and propose a novel taxonomy by which we can classify them. Specifically, we propose three major categories: (1) logically-informed embedding approaches, (2) embedding approaches with logical constraints, and (3) rule learning approaches. Alongside the taxonomy, we provide a tabular overview of the approaches and links to their source code, if available, for more direct comparison. Finally, we discuss the unique characteristics and limitations of these methods, then propose several prospective directions toward which this field of research could evolve.

Lauren Nicole DeLong, Ramon Fernández Mir, Zonglin Ji et al.

Biomedical datasets are often modeled as knowledge graphs (KGs) because they capture the multi-relational, heterogeneous, and dynamic natures of biomedical systems. KG completion (KGC), can, therefore, help researchers make predictions to inform tasks like drug repositioning. While previous approaches for KGC were either rule-based or embedding-based, hybrid approaches based on neurosymbolic artificial intelligence are becoming more popular. Many of these methods possess unique characteristics which make them even better suited toward biomedical challenges. Here, we survey such approaches with an emphasis on their utilities and prospective benefits for biomedicine.