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Collaborative Profile-QSAR: A Natural Platform for Building Collaborative Models among Competing Companies

Martin, Eric and Zhu, Xiangwei (2021) Collaborative Profile-QSAR: A Natural Platform for Building Collaborative Models among Competing Companies. Journal of chemical information and modeling, 61 (4). pp. 1603-1616. ISSN 1549960X


Massively multitask bioactivity models that transfer learning between thousands of assays have been shown to work dramatically better than separate models trained on each individual assay. In particular, the applicability domain for a given model can expand from compounds similar to those tested in that specific assay to those tested across the full complement of contributing assays. If many large companies would share their assay data and train models on the superset, predictions should be better than what each company can do alone. However, a company's compounds, targets, and activities are among their most guarded trade secrets. Strategies have been proposed to share just the individual collaborators' models, without exposing any of the training data. Profile-QSAR (pQSAR) is a two-level, multitask, stacked model. It uses profiles of level-1 predictions from single-task models for thousands of assays as compound descriptors for level-2 models. This work describes its simple and natural adaptation to safe collaboration by model sharing. Broad model sharing has not yet been implemented across multiple large companies, so there are numerous unanswered questions. Novartis was formed from several mergers and acquisitions. In principle, this should allow an internal simulation of model sharing. In practice, the lack of metadata about the origins of compounds and assays made this difficult. Nevertheless, we have attempted to simulate this process and propose some findings: multitask pQSAR is always an improvement over single-task models; collaborative multitask modeling did not improve predictions on internal compounds; collaboration did improve predictions for external compounds but far less than the purely internal multitask modeling for internal compounds; collaborative models for external compounds increasingly improve as overlap between compound collections increases; combining profiles from inside and outside the company is not best, with internal predictions better using only the inside profile and external using only the outside profile, but a consensus of models using all three profiles is best on external compounds and a good compromise on internal compounds. We anticipate similar results from other model-sharing approaches. Indeed, since collaborative pQSAR through model sharing is mathematically identical to pQSAR using actual shared data, we believe our conclusions should apply to collaborative modeling by any current method even including the unlikely scenario of directly sharing all chemical structures and assay data.

Item Type: Article
Date Deposited: 18 May 2021 00:45
Last Modified: 18 May 2021 00:45


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