Sparser2Sparse: Single-shot Sparser-to-Sparse Learning for Spatial Transcriptomics Imputation with Natural Image Co-learning

Spatial transcriptomics (ST) has revolutionized biomedical research by enabling high resolution gene expression profiling within tissues. However, the high cost and scarcity of high resolution ST data remain significant challenges. We present Single-shot Sparser-to-Sparse (S2S-ST), a novel framework for accurate ST imputation that requires only a single and low-cost sparsely sampled ST dataset alongside widely available natural images for co-training. Our approach integrates three key innovations: (1) a sparser-to-sparse self-supervised learning strategy that leverages intrinsic spatial patterns in ST data, (2) cross-domain co-learning with natural images to enhance feature representation, and (3) a Cascaded Data Consistent Imputation Network (CDCIN) that iteratively refines predictions while preserving sampled gene data fidelity. Extensive experiments on diverse tissue types, including breast cancer, liver, and lymphoid tissue, demonstrate that our method outperforms state-of-the-art approaches in imputation accuracy. By enabling robust ST reconstruction from sparse inputs, our framework significantly reduces reliance on costly high resolution data, facilitating potential broader adoption in biomedical research and clinical applications.

AMA-SAM: Adversarial Multi-Domain Alignment of Segment Anything Model for High-Fidelity Histology Nuclei Segmentation

Accurate segmentation of cell nuclei in histopathology images is essential for numerous biomedical research and clinical applications. However, existing cell nucleus segmentation methods only consider a single dataset (i.e., primary domain), while neglecting to leverage supplementary data from diverse sources (i.e., auxiliary domains) to reduce overfitting and enhance the performance. Although incorporating multiple datasets could alleviate overfitting, it often exacerbates performance drops caused by domain shifts. In this work, we introduce Adversarial Multi-domain Alignment of Segment Anything Model (AMA-SAM) that extends the Segment Anything Model (SAM) to overcome these obstacles through two key innovations. First, we propose a Conditional Gradient Reversal Layer (CGRL), a multi-domain alignment module that harmonizes features from diverse domains to promote domain-invariant representation learning while preserving crucial discriminative features for the primary dataset. Second, we address SAM's inherent low-resolution output by designing a High-Resolution Decoder (HR-Decoder), which directly produces fine-grained segmentation maps in order to capture intricate nuclei boundaries in high-resolution histology images. To the best of our knowledge, this is the first attempt to adapt SAM for multi-dataset learning with application to histology nuclei segmentation. We validate our method on several publicly available datasets, demonstrating consistent and significant improvements over state-of-the-art approaches.