A Deep Generative Model for the Design of Synthesizable Ionizable Lipids

Lipid nanoparticles (LNPs) are vital in modern biomedicine, enabling the effective delivery of mRNA for vaccines and therapies by protecting it from rapid degradation. Among the components of LNPs, ionizable lipids play a key role in RNA protection and facilitate its delivery into the cytoplasm. However, designing ionizable lipids is complex. Deep generative models can accelerate this process and explore a larger candidate space compared to traditional methods. Due to the structural differences between lipids and small molecules, existing generative models used for small molecule generation are unsuitable for lipid generation. To address this, we developed a deep generative model specifically tailored for the discovery of ionizable lipids. Our model generates novel ionizable lipid structures and provides synthesis paths using synthetically accessible building blocks, addressing synthesizability. This advancement holds promise for streamlining the development of lipid-based delivery systems, potentially accelerating the deployment of new therapeutic agents, including mRNA vaccines and gene therapies.

Generative Model for Synthesizing Ionizable Lipids: A Monte Carlo Tree Search Approach

Ionizable lipids are essential in developing lipid nanoparticles (LNPs) for effective messenger RNA (mRNA) delivery. While traditional methods for designing new ionizable lipids are typically time-consuming, deep generative models have emerged as a powerful solution, significantly accelerating the molecular discovery process. However, a practical challenge arises as the molecular structures generated can often be difficult or infeasible to synthesize. This project explores Monte Carlo tree search (MCTS)-based generative models for synthesizable ionizable lipids. Leveraging a synthetically accessible lipid building block dataset and two specialized predictors to guide the search through chemical space, we introduce a policy network guided MCTS generative model capable of producing new ionizable lipids with available synthesis pathways.

Training Robust Deep Physiological Measurement Models with Synthetic Video-based Data

Recent advances in supervised deep learning techniques have demonstrated the possibility to remotely measure human physiological vital signs (e.g., photoplethysmograph, heart rate) just from facial videos. However, the performance of these methods heavily relies on the availability and diversity of real labeled data. Yet, collecting large-scale real-world data with high-quality labels is typically challenging and resource intensive, which also raises privacy concerns when storing personal bio-metric data. Synthetic video-based datasets (e.g., SCAMPS \cite{mcduff2022scamps}) with photo-realistic synthesized avatars are introduced to alleviate the issues while providing high-quality synthetic data. However, there exists a significant gap between synthetic and real-world data, which hinders the generalization of neural models trained on these synthetic datasets. In this paper, we proposed several measures to add real-world noise to synthetic physiological signals and corresponding facial videos. We experimented with individual and combined augmentation methods and evaluated our framework on three public real-world datasets. Our results show that we were able to reduce the average MAE from 6.9 to 2.0.