Ahtisham Fazeel Abbasi

arXiv2026

GC-MoE: Genomics-Guided Cell-Type-Specific Mixture of Experts for Histology-Based Single-Cell Spatial Transcriptomics

Histology-based single-cell spatial transcriptomics (ST) estimation aims to predict gene expression for individual cells from histopathological images and cell locations, reducing the need for costly single-cell ST measurements. Unlike existing histology-to-ST methods that mainly predict spot-level profiles for local regions containing multiple cells, this task requires modeling cell-to-cell expression variability, which is strongly structured by cell type. We propose Genomics-Guided Cell-Type-Specific Mixture-of-Experts (GC-MoE), which estimates cell-type probabilities with a routing network and softly combines cell-type-specific experts for gene expression prediction. To further encode cell-type-dependent gene programs, we introduce the Cell-Type-Specific Co-Expression-Aware Predictor (CAP), together with a lightweight Cell-to-Cell Interaction Attention (C2CA) module for neighboring-cell context. Experiments and ablations on public single-cell ST datasets show consistent improvements over existing single-cell and adapted spot-level baselines.

cs.CV↗

arXiv2026

A Large-Scale Comparative Analysis of Imputation Methods for Single-Cell RNA Sequencing Data

Background: Single-cell RNA sequencing (scRNA-seq) enables gene expression profiling at cellular resolution but is inherently affected by sparsity caused by dropout events, where expressed genes are recorded as zeros due to technical limitations. These artifacts distort gene expression distributions and compromise downstream analyses. Numerous imputation methods have been proposed to recover latent transcriptional signals. These methods range from traditional statistical models to deep learning (DL)-based methods. However, their comparative performance remains unclear, as existing benchmarks evaluate only a limited subset of methods, datasets, and downstream analyses. Results: We present a comprehensive benchmark of 15 scRNA-seq imputation methods spanning 7 methodological categories, including traditional and DL-based methods. Methods are evaluated across 30 datasets from 10 experimental protocols on 6 downstream analyses. Results show that traditional methods, such as model-based, smoothing-based, and low-rank matrix-based methods, generally outperform DL-based methods, including diffusion-based, GAN-based, GNN-based, and autoencoder-based methods. In addition, strong performance in numerical gene expression recovery does not necessarily translate into improved biological interpretability in downstream analyses, including cell clustering, differential expression analysis, marker gene analysis, trajectory analysis, and cell type annotation. Furthermore, method performance varies substantially across datasets, protocols, and downstream analyses, with no single method consistently outperforming others. Conclusions: Our findings provide practical guidance for selecting imputation methods tailored to specific analytical objectives and underscore the importance of task-specific evaluation when assessing imputation performance in scRNA-seq data analysis.

q-bio.GN↗