Self-supervised learning (SSL) has proven to be a powerful approach for extracting biologically meaningful representations from single-cell data. To advance our understanding of SSL methods applied to single-cell data, we present scSSL-Bench, a comprehensive benchmark that evaluates nineteen SSL methods. Our evaluation spans nine datasets and focuses on three common downstream tasks: batch correction, cell type annotation, and missing modality prediction. Furthermore, we systematically assess various data augmentation strategies. Our analysis reveals task-specific trade-offs: the specialized single-cell frameworks, scVI, CLAIRE, and the finetuned scGPT excel at uni-modal batch correction, while generic SSL methods, such as VICReg and SimCLR, demonstrate superior performance in cell typing and multi-modal data integration. Random masking emerges as the most effective augmentation technique across all tasks, surpassing domain-specific augmentations. Notably, our results indicate the need for a specialized single-cell multi-modal data integration framework. scSSL-Bench provides a standardized evaluation platform and concrete recommendations for applying SSL to single-cell analysis, advancing the convergence of deep learning and single-cell genomics.

The hierarchical structure inherent in many real-world datasets makes the modeling of such hierarchies a crucial objective in both unsupervised and supervised machine learning. While recent advancements have introduced deep architectures specifically designed for hierarchical clustering, we adopt a critical perspective on this line of research. Our findings reveal that these methods face significant limitations in scalability and performance when applied to realistic datasets. Given these findings, we present an alternative approach and introduce a lightweight method that builds on pre-trained non-hierarchical clustering models. Remarkably, our approach outperforms specialized deep models for hierarchical clustering, and it is broadly applicable to any pre-trained clustering model that outputs logits, without requiring any fine-tuning. To highlight the generality of our approach, we extend its application to a supervised setting, demonstrating its ability to recover meaningful hierarchies from a pre-trained ImageNet classifier. Our results establish a practical and effective alternative to existing deep hierarchical clustering methods, with significant advantages in efficiency, scalability and performance.

In the quest for efficient and robust learning methods, combining unsupervised state representation learning and reinforcement learning (RL) could offer advantages for scaling RL algorithms by providing the models with a useful inductive bias. For achieving this, an encoder is trained in an unsupervised manner with two state representation methods, a variational autoencoder and a contrastive estimator. The learned features are then fed to the actor-critic RL algorithm Proximal Policy Optimization (PPO) to learn a policy for playing Open AI's car racing environment. Hence, such procedure permits to decouple state representations from RL-controllers. For the integration of RL with unsupervised learning, we explore various designs for variational autoencoders and contrastive learning. The proposed method is compared to a deep network trained directly on pixel inputs with PPO. The results show that the proposed method performs slightly worse than directly learning from pixel inputs; however, it has a more stable learning curve, a substantial reduction of the buffer size, and requires optimizing 88% fewer parameters. These results indicate that the use of pre-trained state representations has several benefits for solving RL tasks.

Learning from different data types is a long-standing goal in machine learning research, as multiple information sources co-occur when describing natural phenomena. However, existing generative models that approximate a multimodal ELBO rely on difficult or inefficient training schemes to learn a joint distribution and the dependencies between modalities. In this work, we propose a novel, efficient objective function that utilizes the Jensen-Shannon divergence for multiple distributions. It simultaneously approximates the unimodal and joint multimodal posteriors directly via a dynamic prior. In addition, we theoretically prove that the new multimodal JS-divergence (mmJSD) objective optimizes an ELBO. In extensive experiments, we demonstrate the advantage of the proposed mmJSD model compared to previous work in unsupervised, generative learning tasks.