iCubed (Institute, Industry, Innovation) seminars invite DSI Industry Affiliates to give technical talks on work going on in their domain. Join to learn about real-world uses of data science and opportunities with Industry Affiliates.

Guest Speaker

William J. Godinez, Associate Director (AD) and Senior Principal Data Scientist at Novartis Institutes for BioMedical Research (NIBR)

Moderated By: Jessica Rodriguez, Industry Engagement and Outreach Officer, The Data Science Institute

Details & Recording

Thursday, October 21 (2:00 PM – 3:00 PM ET) – Virtual

Talk Information

JAEGER – Hunting for Antimalarials with Generative Chemistry

Abstract: Recent advances in generative modeling allow designing novel molecules through deep artificial neural networks. One such neural network model, the Junction Tree Variational Auto- Encoder (JT-VAE), excels at proposing chemically valid structures. Based on JT-VAE, we built a generative modeling approach (JAEGER) for finding novel chemical matter with desired bioactivity. Using JAEGER, we designed compounds to inhibit malaria. To prioritize the compounds for synthesis, we used the in-house Profile-QSAR (pQSAR) program, a massively-multitask bioactivity model based on 12,000 Novartis assays. Based on the pQSAR activity predictions, we selected, synthesized, and experimentally profiled two compounds. Both compounds exhibited low nanomolar activity in a malaria proliferation assay as well as a biochemical assay measuring activity against PI(4)K, which is an essential kinase that regulates intracellular development in malaria. The compounds also showed low activity in a cytotoxicity assay. Our findings show that JAEGER is a viable approach for finding novel active compounds for drug discovery. DOI: 10.33774/chemrxiv-2021-5t5xx

Opportunity: Chemical Biology & Therapeutics, Data Science Expert Novartis Bay Area. See job details and application here.