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Marghi, Y.

Publications and source records attributed to Marghi, Y..

2 recordsLinked to original sources

Bloom unifies brain cell representations across modalities and contexts

Multimodal genomic datasets now profile mammalian brain cells across anatomical regions, developmental stages, disease states, and species. Learning shared representations that capture cellular diversity across these heterogeneous observations remains a central challenge. Here, we introduce Bloom, a transformer-based model that represents cells using gene expression, chromatin accessibility, or both. Bloom is trained on 300,000 adult mouse brain cells with paired measurements, randomly sampled with broad-subclass balancing--approximately 100-fold fewer cells than used by comparable pre-trained models. By combining genomic sequence embeddings with randomly sampled multimodal cell views, Bloom outperforms unimodal cell models in resolving brain-wide cell types and in annotation, regression, and label-transfer tasks. Its attention patterns reveal cell-type-dependent associations among genomic loci, including pairs separated by millions of base pairs. These results establish Bloom as a data-efficient framework for integrating multimodal brain cell measurements and generating hypotheses about cell-type-specific genomic relationships.

bioinformatics↗

Joint inference of discrete cell types and continuous type-specific variability in single-cell datasets with MMIDAS

Reproducible definition and identification of cell types is essential to enable investigations into their biological function, and understanding their relevance in the context of development, disease and evolution. Current approaches model variability in data as continuous latent factors, followed by clustering as a separate step, or immediately apply clustering on the data. We show that such approaches can suffer from qualitative mistakes in identifying cell types robustly, particularly when the number of such cell types is in the hundreds or even thousands. Here, we propose an unsupervised method, MMIDAS, which combines a generalized mixture model with a multi-armed deep neural network, to jointly infer the discrete type and continuous type-specific variability. Using four recent datasets of brain cells spanning different technologies, species, and conditions, we demonstrate that MMIDAS can identify reproducible cell types and infer cell type-dependent continuous variability in both uni-modal and multi-modal datasets.

neuroscience↗