Julien Roy

Pietro Lio

Generative models see increasing use in computer-aided drug design. However, while performing well at capturing distributions of molecular m… (see more)otifs, they often produce synthetically inaccessible molecules. To address this, we introduce SynFlowNet, a GFlowNet model whose action space uses chemical reactions and buyable reactants to sequentially build new molecules. By incorporating forward synthesis as an explicit constraint of the generative mechanism, we aim at bridging the gap between in silico molecular generation and real world synthesis capabilities. We evaluate our approach using synthetic accessibility scores and an independent retrosynthesis tool to assess the synthesizability of our compounds, and motivate the choice of GFlowNets through considerable improvement in sample diversity compared to baselines. Additionally, we identify challenges with reaction encodings that can complicate traversal of the MDP in the backward direction. To address this, we introduce various strategies for learning the GFlowNet backward policy and thus demonstrate how additional constraints can be integrated into the GFlowNet MDP framework. This approach enables our model to successfully identify synthesis pathways for previously unseen molecules.

2025-01-01

ICLR (published)

Efficient Biological Data Acquisition through Inference Set Design

Ihor Neporozhnii

Jason Hartford

In drug discovery, highly automated high-throughput laboratories are used to screen a large number of compounds in search of effective drugs… (see more). These experiments are expensive, so one might hope to reduce their cost by only experimenting on a subset of the compounds, and predicting the outcomes of the remaining experiments. In this work, we model this scenario as a sequential subset selection problem: we aim to select the smallest set of candidates in order to achieve some desired level of accuracy for the system as a whole. Our key observation is that, if there is heterogeneity in the difficulty of the prediction problem across the input space, selectively obtaining the labels for the hardest examples in the acquisition pool will leave only the relatively easy examples to remain in the inference set, leading to better overall system performance. We call this mechanism inference set design, and propose the use of a confidence-based active learning solution to prune out these challenging examples. Our algorithm includes an explicit stopping criterion that interrupts the acquisition loop when it is sufficiently confident that the system has reached the target performance. Our empirical studies on image and molecular datasets, as well as a real-world large-scale biological assay, show that active learning for inference set design leads to significant reduction in experimental cost while retaining high system performance.

2024-10-25

ArXiv (preprint)

Efficient Biological Data Acquisition through Inference Set Design

Ihor Neporozhnii

Jason Hartford

In drug discovery, highly automated high-throughput laboratories are used to screen a large number of compounds in search of effective drugs… (see more). These experiments are expensive, so one might hope to reduce their cost by only experimenting on a subset of the compounds, and predicting the outcomes of the remaining experiments. In this work, we model this scenario as a sequential subset selection problem: we aim to select the smallest set of candidates in order to achieve some desired level of accuracy for the system as a whole. Our key observation is that, if there is heterogeneity in the difficulty of the prediction problem across the input space, selectively obtaining the labels for the hardest examples in the acquisition pool will leave only the relatively easy examples to remain in the inference set, leading to better overall system performance. We call this mechanism inference set design, and propose the use of a confidence-based active learning solution to prune out these challenging examples. Our algorithm includes an explicit stopping criterion that interrupts the acquisition loop when it is sufficiently confident that the system has reached the target performance. Our empirical studies on image and molecular datasets, as well as a real-world large-scale biological assay, show that active learning for inference set design leads to significant reduction in experimental cost while retaining high system performance.

2024-10-25

ArXiv (preprint)

SynFlowNet: Towards Molecule Design with Guaranteed Synthesis Pathways

M. Cretu

Charles Harris

Pietro Lio

2024-01-01

arXiv.org (preprint)

SynFlowNet: Towards Molecule Design with Guaranteed Synthesis Pathways

M. Cretu

Charles Harris

Pietro Lio

2024-01-01

arXiv.org (preprint)

Goal-conditioned GFlowNets for Controllable Multi-Objective Molecular Design

In recent years, in-silico molecular design has received much attention from the machine learning community. When designing a new compound f… (see more)or pharmaceutical applications, there are usually multiple properties of such molecules that need to be optimised: binding energy to the target, synthesizability, toxicity, EC50, and so on. While previous approaches have employed a scalarization scheme to turn the multi-objective problem into a preference-conditioned single objective, it has been established that this kind of reduction may produce solutions that tend to slide towards the extreme points of the objective space when presented with a problem that exhibits a concave Pareto front. In this work we experiment with an alternative formulation of goal-conditioned molecular generation to obtain a more controllable conditional model that can uniformly explore solutions along the entire Pareto front.

2023-06-23

ICML.cc/2023/Workshop/DeployableGenerativeAI (published)

openreview.net

Direct Behavior Specification via Constrained Reinforcement Learning

Chris J Pal

The standard formulation of Reinforcement Learning lacks a practical way of specifying what are admissible and forbidden behaviors. Most oft… (see more)en, practitioners go about the task of behavior specification by manually engineering the reward function, a counter-intuitive process that requires several iterations and is prone to reward hacking by the agent. In this work, we argue that constrained RL, which has almost exclusively been used for safe RL, also has the potential to significantly reduce the amount of work spent for reward specification in applied RL projects. To this end, we propose to specify behavioral preferences in the CMDP framework and to use Lagrangian methods to automatically weigh each of these behavioral constraints. Specifically, we investigate how CMDPs can be adapted to solve goal-based tasks while adhering to several constraints simultaneously. We evaluate this framework on a set of continuous control tasks relevant to the application of Reinforcement Learning for NPC design in video games.

2022-06-28

Proceedings of the 39th International Conference on Machine Learning (published)

proceedings.mlr.press

Adversarial Soft Advantage Fitting: Imitation Learning without Policy Optimization

Adversarial imitation learning alternates between learning a discriminator -- which tells apart expert's demonstrations from generated ones … (see more)-- and a generator's policy to produce trajectories that can fool this discriminator. This alternated optimization is known to be delicate in practice since it compounds unstable adversarial training with brittle and sample-inefficient reinforcement learning. We propose to remove the burden of the policy optimization steps by leveraging a novel discriminator formulation. Specifically, our discriminator is explicitly conditioned on two policies: the one from the previous generator's iteration and a learnable policy. When optimized, this discriminator directly learns the optimal generator's policy. Consequently, our discriminator's update solves the generator's optimization problem for free: learning a policy that imitates the expert does not require an additional optimization loop. This formulation effectively cuts by half the implementation and computational burden of adversarial imitation learning algorithms by removing the reinforcement learning phase altogether. We show on a variety of tasks that our simpler approach is competitive to prevalent imitation learning methods.