Hybrid Generative AI for De Novo Design of Co-Crystals with Enhanced Tabletability

Co-crystallization is an accessible way to control physicochemical characteristics of organic crystals, which finds many biomedical applications. In this work, we present Generative Method for Co-crystal Design (GEMCODE), a novel pipeline for automated co-crystal screening based on the hybridization of deep generative models and evolutionary optimization for broader exploration of the target chemical space. GEMCODE enables fast de novo co-crystal design with target tabletability profiles, which is crucial for the development of pharmaceuticals. With a series of experimental studies highlighting validation and discovery cases, we show that GEMCODE is effective even under realistic computational constraints. Furthermore, we explore the potential of language models in generating co-crystals. Finally, we present numerous previously unknown co-crystals predicted by GEMCODE and discuss its potential in accelerating drug development.

Unveiling the Potential of AI for Nanomaterial Morphology Prediction

Creation of nanomaterials with specific morphology remains a complex experimental process, even though there is a growing demand for these materials in various industry sectors. This study explores the potential of AI to predict the morphology of nanoparticles within the data availability constraints. For that, we first generated a new multi-modal dataset that is double the size of analogous studies. Then, we systematically evaluated performance of classical machine learning and large language models in prediction of nanomaterial shapes and sizes. Finally, we prototyped a text-to-image system, discussed the obtained empirical results, as well as the limitations and promises of existing approaches.

Self-supervised learning for analysis of temporal and morphological drug effects in cancer cell imaging data

In this work, we propose two novel methodologies to study temporal and morphological phenotypic effects caused by different experimental conditions using imaging data. As a proof of concept, we apply them to analyze drug effects in 2D cancer cell cultures. We train a convolutional autoencoder on 1M images dataset with random augmentations and multi-crops to use as feature extractor. We systematically compare it to the pretrained state-of-the-art models. We further use the feature extractor in two ways. First, we apply distance-based analysis and dynamic time warping to cluster temporal patterns of 31 drugs. We identify clusters allowing annotation of drugs as having cytotoxic, cytostatic, mixed or no effect. Second, we implement an adversarial/regularized learning setup to improve classification of 31 drugs and visualize image regions that contribute to the improvement. We increase top-3 classification accuracy by 8% on average and mine examples of morphological feature importance maps. We provide the feature extractor and the weights to foster transfer learning applications in biology. We also discuss utility of other pretrained models and applicability of our methods to other types of biomedical data.

Comparing representations of biological data learned with different AI paradigms, augmenting and cropping strategies

Recent advances in computer vision and robotics enabled automated large-scale biological image analysis. Various machine learning approaches have been successfully applied to phenotypic profiling. However, it remains unclear how they compare in terms of biological feature extraction. In this study, we propose a simple CNN architecture and implement 4 different representation learning approaches. We train 16 deep learning setups on the 770k cancer cell images dataset under identical conditions, using different augmenting and cropping strategies. We compare the learned representations by evaluating multiple metrics for each of three downstream tasks: i) distance-based similarity analysis of known drugs, ii) classification of drugs versus controls, iii) clustering within cell lines. We also compare training times and memory usage. Among all tested setups, multi-crops and random augmentations generally improved performance across tasks, as expected. Strikingly, self-supervised (implicit contrastive learning) models showed competitive performance being up to 11 times faster to train. Self-supervised regularized learning required the most of memory and computation to deliver arguably the most informative features. We observe that no single combination of augmenting and cropping strategies consistently results in top performance across tasks and recommend prospective research directions.