Fuzz Testing Molecular Representation Using Deep Variational Anomaly Generation
Researchers are developing increasingly robust molecular representations, motivating the need for thorough methods to stress-test and validate them. Here, we use a variational auto-encoder (VAE), an unsupervised deep learning model, to generate anomalous examples of SELF-referencIng Embedded Strings (SELFIES), a popular molecular string format. These anomalies defy the assertion that all SELFIES convert into valid SMILES strings. Interestingly, we find specific regions within the VAE's internal landscape (latent space), whose decoding frequently generates inconvertible SELFIES anomalies. The model's internal landscape self-organization helps with exploring factors affecting molecular representation reliability. We show how VAEs and similar anomaly generation methods can empirically stress-test molecular representation robustness. Additionally, we investigate reasons for the invalidity of some discovered SELFIES strings (version 2.1.1) and suggest changes to improve them, aiming to spark ongoing molecular representation improvement.
Authors
- Michael J. Keiser (ORCID: https://orcid.org/0000-0002-1240-2192)
- Victor H. R. Nogueira (ORCID: https://orcid.org/0000-0003-0755-2521)
- Rafael V. C. Guido (ORCID: https://orcid.org/0000-0002-7187-0818)
- Rishabh Sharma (ORCID: https://orcid.org/0000-0002-8515-082X)
Institutions
- University of California, San Francisco (US)
- FZU ‒ Institute of Physics of the Academy of Sciences of the Czech Republic (CZ)
- Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung (IPK) (DE)
Publication Details
- Journal
- Journal of Chemical Information and Modeling
- Published
- 2025-02-05
- DOI
- https://doi.org/10.1021/acs.jcim.4c01876
- Citations
- 1
- Primary Topic
- Machine Learning in Materials Science
- Type
- article
- Field-Weighted Citation Impact
- 0.52
Funders
- Silicon Valley Community Foundation
- Chan Zuckerberg Initiative
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior