Jon Paul Janet

David Buterez, Jon Paul Janet, Steven J. Kiddle et al.

An effective aggregation of node features into a graph-level representation via readout functions is an essential step in numerous learning tasks involving graph neural networks. Typically, readouts are simple and non-adaptive functions designed such that the resulting hypothesis space is permutation invariant. Prior work on deep sets indicates that such readouts might require complex node embeddings that can be difficult to learn via standard neighborhood aggregation schemes. Motivated by this, we investigate the potential of adaptive readouts given by neural networks that do not necessarily give rise to permutation invariant hypothesis spaces. We argue that in some problems such as binding affinity prediction where molecules are typically presented in a canonical form it might be possible to relax the constraints on permutation invariance of the hypothesis space and learn a more effective model of the affinity by employing an adaptive readout function. Our empirical results demonstrate the effectiveness of neural readouts on more than 40 datasets spanning different domains and graph characteristics. Moreover, we observe a consistent improvement over standard readouts (i.e., sum, max, and mean) relative to the number of neighborhood aggregation iterations and different convolutional operators.

Gökçe Geylan, Jon Paul Janet, Alessandro Tibo et al.

Peptides play a crucial role in the drug design and discovery whether as a therapeutic modality or a delivery agent. Non-natural amino acids (NNAAs) have been used to enhance the peptide properties from binding affinity, plasma stability to permeability. Incorporating novel NNAAs facilitates the design of more effective peptides with improved properties. The generative models used in the field, have focused on navigating the peptide sequence space. The sequence space is formed by combinations of a predefined set of amino acids. However, there is still a need for a tool to explore the peptide landscape beyond this enumerated space to unlock and effectively incorporate de novo design of new amino acids. To thoroughly explore the theoretical chemical space of the peptides, we present PepINVENT, a novel generative AI-based tool as an extension to the small molecule molecular design platform, REINVENT. PepINVENT navigates the vast space of natural and non-natural amino acids to propose valid, novel, and diverse peptide designs. The generative model can serve as a central tool for peptide-related tasks, as it was not trained on peptides with specific properties or topologies. The prior was trained to understand the granularity of peptides and to design amino acids for filling the masked positions within a peptide. PepINVENT coupled with reinforcement learning enables the goal-oriented design of peptides using its chemistry-informed generative capabilities. This study demonstrates PepINVENT's ability to explore the peptide space with unique and novel designs, and its capacity for property optimization in the context of therapeutically relevant peptides. Our tool can be employed for multi-parameter learning objectives, peptidomimetics, lead optimization, and variety of other tasks within the peptide domain.

David Buterez, Jon Paul Janet, Dino Oglic et al.

There has been a recent surge in transformer-based architectures for learning on graphs, mainly motivated by attention as an effective learning mechanism and the desire to supersede handcrafted operators characteristic of message passing schemes. However, concerns over their empirical effectiveness, scalability, and complexity of the pre-processing steps have been raised, especially in relation to much simpler graph neural networks that typically perform on par with them across a wide range of benchmarks. To tackle these shortcomings, we consider graphs as sets of edges and propose a purely attention-based approach consisting of an encoder and an attention pooling mechanism. The encoder vertically interleaves masked and vanilla self-attention modules to learn an effective representations of edges, while allowing for tackling possible misspecifications in input graphs. Despite its simplicity, the approach outperforms fine-tuned message passing baselines and recently proposed transformer-based methods on more than 70 node and graph-level tasks, including challenging long-range benchmarks. Moreover, we demonstrate state-of-the-art performance across different tasks, ranging from molecular to vision graphs, and heterophilous node classification. The approach also outperforms graph neural networks and transformers in transfer learning settings, and scales much better than alternatives with a similar performance level or expressive power.

Hampus Gummesson Svensson, Ola Engkvist, Jon Paul Janet et al.

In many real-world applications, evaluating the quality of instances is costly and time-consuming, e.g., human feedback and physics simulations, in contrast to proposing new instances. In particular, this is even more critical in reinforcement learning, since it relies on interactions with the environment (i.e., new instances) that must be evaluated to provide a reward signal for learning. At the same time, performing sufficient exploration is crucial in reinforcement learning to find high-rewarding solutions, meaning that the agent should observe and learn from a diverse set of experiences to find different solutions. Thus, we argue that learning from a diverse mini-batch of experiences can have a large impact on the exploration and help mitigate mode collapse. In this paper, we introduce mini-batch diversification for reinforcement learning and study this framework in the context of a real-world problem, namely, drug discovery. We extensively evaluate how our proposed framework can enhance the effectiveness of chemical exploration in de novo drug design, where finding diverse and high-quality solutions is crucial. Our experiments demonstrate that our proposed diverse mini-batch selection framework can substantially enhance the diversity of solutions while maintaining high-quality solutions. In drug discovery, such an outcome can potentially lead to fulfilling unmet medical needs faster.

Daniel R. Harper, Aditya Nandy, Naveen Arunachalam et al.

Strategies for machine-learning(ML)-accelerated discovery that are general across materials composition spaces are essential, but demonstrations of ML have been primarily limited to narrow composition variations. By addressing the scarcity of data in promising regions of chemical space for challenging targets like open-shell transition-metal complexes, general representations and transferable ML models that leverage known relationships in existing data will accelerate discovery. Over a large set (ca. 1000) of isovalent transition-metal complexes, we quantify evident relationships for different properties (i.e., spin-splitting and ligand dissociation) between rows of the periodic table (i.e., 3d/4d metals and 2p/3p ligands). We demonstrate an extension to graph-based revised autocorrelation (RAC) representation (i.e., eRAC) that incorporates the effective nuclear charge alongside the nuclear charge heuristic that otherwise overestimates dissimilarity of isovalent complexes. To address the common challenge of discovery in a new space where data is limited, we introduce a transfer learning approach in which we seed models trained on a large amount of data from one row of the periodic table with a small number of data points from the additional row. We demonstrate the synergistic value of the eRACs alongside this transfer learning strategy to consistently improve model performance. Analysis of these models highlights how the approach succeeds by reordering the distances between complexes to be more consistent with the periodic table, a property we expect to be broadly useful for other materials domains.