Navin Rathna Kumar

Lei Tong, Adam Corrigan, Navin Rathna Kumar et al.

Cell line authentication plays a crucial role in the biomedical field, ensuring researchers work with accurately identified cells. Supervised deep learning has made remarkable strides in cell line identification by studying cell morphological features through cell imaging. However, batch effects, a significant issue stemming from the different times at which data is generated, lead to substantial shifts in the underlying data distribution, thus complicating reliable differentiation between cell lines from distinct batch cultures. To address this challenge, we introduce CLANet, a pioneering framework for cross-batch cell line identification using brightfield images, specifically designed to tackle three distinct batch effects. We propose a cell cluster-level selection method to efficiently capture cell density variations, and a self-supervised learning strategy to manage image quality variations, thus producing reliable patch representations. Additionally, we adopt multiple instance learning(MIL) for effective aggregation of instance-level features for cell line identification. Our innovative time-series segment sampling module further enhances MIL's feature-learning capabilities, mitigating biases from varying incubation times across batches. We validate CLANet using data from 32 cell lines across 93 experimental batches from the AstraZeneca Global Cell Bank. Our results show that CLANet outperforms related approaches (e.g. domain adaptation, MIL), demonstrating its effectiveness in addressing batch effects in cell line identification.

Lei Tong, Xujing Yao, Adam Corrigan et al.

High-Content Screening routinely generates massive volumes of cell painting images for phenotypic profiling. However, technical variations across experimental executions inevitably induce biological batch (bio-batch) effects. These cause covariate shifts and degrade the generalization of deep learning models on unseen data. Existing batch correction methods typically rely on additional prior knowledge (e.g., treatment or cell culture information) or struggle to generalize to unseen bio-batches. In this work, we frame bio-batch mitigation as a Domain Generalization (DG) problem and propose Adversarial Batch Representation Augmentation (ABRA). ABRA explicitly models batch-wise statistical fluctuations by parameterizing feature statistics as structured uncertainties. Through a min-max optimization framework, it actively synthesizes worst-case bio-batch perturbations in the representation space, guided by a strict angular geometric margin to preserve fine-grained class discriminability. To prevent representation collapse during this adversarial exploration, we introduce a synergistic distribution alignment objective. Extensive evaluations on the large-scale RxRx1 and RxRx1-WILDS benchmarks demonstrate that ABRA establishes a new state-of-the-art for siRNA perturbation classification.