Tom George Grigg

Tom George Grigg, Mason Burlage, Oliver Brook Scott et al.

Exhaustive virtual screening is highly informative but often intractable against the expensive objective functions involved in modern drug discovery. This problem is exacerbated in combinatorial contexts such as multi-vector expansion, where molecular spaces can quickly become ultra-large. Here, we introduce Scalable Active Learning via Synthon Acquisition (SALSA): a simple algorithm applicable to multi-vector expansion which extends pool-based active learning to non-enumerable spaces by factoring modeling and acquisition over synthon or fragment choices. Through experiments on ligand- and structure-based objectives, we highlight SALSA's sample efficiency, and its ability to scale to spaces of trillions of compounds. Further, we demonstrate application toward multi-parameter objective design tasks on three protein targets - finding SALSA-generated molecules have comparable chemical property profiles to known bioactives, and exhibit greater diversity and higher scores over an industry-leading generative approach.

Tom George Grigg, Dan Busbridge, Jason Ramapuram et al.

Despite the success of a number of recent techniques for visual self-supervised deep learning, there has been limited investigation into the representations that are ultimately learned. By leveraging recent advances in the comparison of neural representations, we explore in this direction by comparing a contrastive self-supervised algorithm to supervision for simple image data in a common architecture. We find that the methods learn similar intermediate representations through dissimilar means, and that the representations diverge rapidly in the final few layers. We investigate this divergence, finding that these layers strongly fit to their distinct learning objectives. We also find that the contrastive objective implicitly fits the supervised objective in intermediate layers, but that the reverse is not true. Our work particularly highlights the importance of the learned intermediate representations, and raises critical questions for auxiliary task design.