Arvind Thiagarajan

Konstantin Yatsenko, Arvind Thiagarajan

Generative molecular models for drug design are a promising direction with much active research. In the next phase of computational drug design, such models will need to understand small molecule structure and protein-ligand interactions, and they will need to possess the machinery to generate molecules \textit{de novo}. Incorporating each feature poses a critical challenge. Equally important, yet often treated as secondary, is the ability to grow a molecule from a partial starting point -- a scaffold or fragment supplied by a chemist -- which is the central operation of lead optimization. We present Sesame (Spatial Evoformer for a Structure-Aware Molecular Engine), a diffusion-based molecular generation model that leverages a novel spatial pairformer module to condition on partial molecular structure and the surrounding protein pocket, both expressed as continuous spatial density maps. This single conditioning mechanism supports both \textit{de novo} generation and fragment-conditioned lead optimization, letting a medicinal chemist prune a hit to a scaffold and have Sesame grow it in productive ways. In addition to this module, we also introduce a diffusion framework for joint denoising of atom types, bond types, and positions, along with a trajectory finetuning scheme that trains on the model's own sampling rollouts to improve generation quality. Sesame is trained on a large corpus of ligand-only and protein-ligand datasets.

Conor O'Brien, Arvind Thiagarajan, Sourav Das et al.

Online advertising has typically been more personalized than offline advertising, through the use of machine learning models and real-time auctions for ad targeting. One specific task, predicting the likelihood of conversion (i.e.\ the probability a user will purchase the advertised product), is crucial to the advertising ecosystem for both targeting and pricing ads. Currently, these models are often trained by observing individual user behavior, but, increasingly, regulatory and technical constraints are requiring privacy-preserving approaches. For example, major platforms are moving to restrict tracking individual user events across multiple applications, and governments around the world have shown steadily more interest in regulating the use of personal data. Instead of receiving data about individual user behavior, advertisers may receive privacy-preserving feedback, such as the number of installs of an advertised app that resulted from a group of users. In this paper we outline the recent privacy-related changes in the online advertising ecosystem from a machine learning perspective. We provide an overview of the challenges and constraints when learning conversion models in this setting. We introduce a novel approach for training these models that makes use of post-ranking signals. We show using offline experiments on real world data that it outperforms a model relying on opt-in data alone, and significantly reduces model degradation when no individual labels are available. Finally, we discuss future directions for research in this evolving area.

Arvind Thiagarajan

Fisher's method prescribes a way to combine p-values from multiple experiments into a single p-value. However, the original method can only determine a combined p-value analytically if all constituent p-values are weighted equally. Here we present, with proof, a method to combine p-values with arbitrary weights.

Arvind Thiagarajan

Order statistics provide an intuition for combining multiple lists of scores over a common index set. This intuition is particularly valuable when the lists to be combined cannot be directly compared in a sensible way. We describe here the advantages of a new method for using joint CDFs of such order statistics to combine score lists. We also present, with proof, a new algorithm for computing such joint CDF values, with runtime linear in the size of the combined list.