Sudip Khadka

Eduardo Hirata-Miyasaki, Soorya Pradeep, Ziwen Liu et al.

We report DynaCLR, a self-supervised method for embedding cell and organelle Dynamics via Contrastive Learning of Representations of time-lapse images. DynaCLR integrates single-cell tracking and time-aware contrastive sampling to learn robust, temporally regularized representations of cell dynamics. DynaCLR embeddings generalize effectively to in-distribution and out-of-distribution datasets, and can be used for several downstream tasks with sparse human annotations. We demonstrate efficient annotations of cell states with a human-in-the-loop using fluorescence and label-free imaging channels. DynaCLR method enables diverse downstream biological analyses: classification of cell division and infection, clustering heterogeneous cell migration patterns, cross-modal distillation of cell states from fluorescence to label-free channel, alignment of asynchronous cellular responses and broken cell tracks, and discovering organelle response due to infection. DynaCLR is a flexible method for comparative analyses of dynamic cellular responses to pharmacological, microbial, and genetic perturbations. We provide PyTorch-based implementations of the model training and inference pipeline (https://github.com/mehta-lab/viscy) and a GUI (https://github.com/czbiohub-sf/napari-iohub) for the visualization and annotation of trajectories of cells in the real space and the embedding space.

Sudip Khadka, L. S. Paudel

Static feature exclusion strategies often fail to prevent bias when hidden dependencies influence the model predictions. To address this issue, we explore a reinforcement learning (RL) framework that integrates bias mitigation and automated feature selection within a single learning process. Unlike traditional heuristic-driven filter or wrapper approaches, our RL agent adaptively selects features using a reward signal that explicitly integrates predictive performance with fairness considerations. This dynamic formulation allows the model to balance generalization, accuracy, and equity throughout the training process, rather than rely exclusively on pre-processing adjustments or post hoc correction mechanisms. In this paper, we describe the construction of a multi-component reward function, the specification of the agents action space over feature subsets, and the integration of this system with ensemble learning. We aim to provide a flexible and generalizable way to select features in environments where predictors are correlated and biases can inadvertently re-emerge.