Learn how to leverage generative AI to support and improve your productivity at work. The next cohort will take place online on April 28 and 30, 2026, in French.
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Spatial transcriptomics has revolutionized our ability to characterize tissues and diseases by contextualizing gene expression with spatial … (see more)organization. Available methods require researchers to either train a model using histology-based annotations or use annotation-free clustering approaches to uncover spatial domains. However, few methods provide researchers with a way to jointly analyze spatial data from both annotation-free and annotation-guided perspectives using consistent inductive biases and levels of interpretability. A single framework with consistent inductive biases ensures coherence and transferability across tasks, reducing the risks of conflicting assumptions. To this end, we propose the Spatial Topic Model (SpaTM), a topic-modeling framework capable of annotation-guided and annotation-free analysis of spatial transcriptomics data. SpaTM can be used to learn gene programs that represent histology-based annotations while providing researchers with the ability to infer spatial domains with an annotation-free approach if manual annotations are limited or noisy. We demonstrate SpaTM’s interpretability with its use of topic mixtures to represent cell states and transcriptional programs and how its intuitive framework facilitates the integration of annotation-guided and annotation-free analyses of spatial data with downstream analyses such as cell type deconvolution. Finally, we demonstrate how both approaches can be used to extend the analysis of large-scale snRNA-seq atlases with the inference of cell proximity and spatial annotations in human brains with Major Depressive Disorder.
Single-cell Assay for Transposase-Accessible Chromatin with sequencing (scATAC-seq) has emerged as a powerful technique for investigating op… (see more)en chromatin landscapes at single-cell resolution. However, analyzing scATAC-seq data remain challenging due to its sparsity and noise. Genome Foundation Models (GFMs), pre-trained on massive DNA sequences, have proven effective at genome analysis. Given that open chromatin regions (OCRs) harbour salient sequence features, we hypothesize that leveraging GFMs’ sequence embeddings can improve the accuracy and generalizability of scATAC-seq modeling. Here, we introduce the Genome Foundation Embedded Topic Model (GFETM), an interpretable deep learning framework that combines GFMs with the Embedded Topic Model (ETM) for scATAC-seq data analysis. By integrating the DNA sequence embeddings extracted by a GFM from OCRs, GFETM demonstrates superior accuracy and generalizability and captures cell-state specific TF activity both with zero-shot inference and attention mechanism analysis. Finally, the topic mixtures inferred by GFETM reveal biologically meaningful epigenomic signatures of kidney diabetes.