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Biology subjects

Geras, A.

Publications and source records attributed to Geras, A..

3 recordsLinked to original sources

ST-Assign: a probabilistic model for joint cell type identification in spatial transcriptomics and single-cell RNA sequencing data

Understanding the intricate composition of tissues in complex living organisms is crucial for unraveling the mechanisms underlying health and disease. This study addresses the challenge of dissecting cell types within tissues by integrating information from two powerful experimental techniques: single-cell RNA-sequencing (scRNA-seq) and spatial transcriptomics (ST). While scRNA-seq offers insights into transcriptional heterogeneity at the cellular level, ST provides spatial information within tissues. Current methods for cell-type annotation in scRNA-seq and mixture decomposition in ST data are often conducted independently, resulting in reduced statistical power and accuracy. To bridge this gap, we propose ST-Assign, a novel hierarchical Bayesian probabilistic model that jointly performs cell-type annotation in scRNA-seq data and cell-type mixture decomposition in ST data. ST-Assign accounts for shared variables such as gene expression profiles and leverages prior knowledge about marker genes, amplifying statistical strength and mitigating experimental noise. The models excellent performance is demonstrated on simulated and real mouse brain data, showcasing accurate cell-type mixture decomposition and cell-type assignment. In comparison to existing tools, ST-Assign demonstrates superior capabilities, particularly in the task of assigning cell types to individual cells. ST-Assign enables exploring the spatial composition of cell types and holds the potential for enhancing our comprehension of diverse biological systems.

bioinformatics↗

Tumoroscope: a probabilistic model for mapping cancer clones in tumor tissues

Spatial and genomic heterogeneity of tumors is the key for cancer progression, treatment, and survival. However, a technology for direct mapping the clones in the tumor tissue based on point mutations is lacking. Here, we propose Tumoroscope, the first probabilistic model that accurately infers cancer clones and their high-resolution localization by integrating pathological images, whole exome sequencing, and spatial transcriptomics data. In contrast to previous methods, Tumoroscope explicitly addresses the problem of deconvoluting the proportions of clones in spatial transcriptomics spots. Applied to a reference prostate cancer dataset and a newly generated breast cancer dataset, Tumoroscope reveals spatial patterns of clone colocalization and mutual exclusion in sub-areas of the tumor tissue. We further infer clone-specific gene expression levels and the most highly expressed genes for each clone. In summary, Tumoroscope enables an integrated study of the spatial, genomic, and phenotypic organization of tumors.

cancer biology↗

Celloscope: a probabilistic model for marker-gene-driven cell type deconvolution in spatial transcriptomics data

Spatial transcriptomics maps gene expression across tissues, posing the challenge of determining the spatial arrangement of different cell types. However, spatial transcriptomics spots contain multiple cells. Therefore, the observed signal comes from mixtures of cells of different types. Here, we propose an innovative probabilistic model, Celloscope, that utilizes established prior knowledge on marker genes for cell type deconvolution from spatial transcriptomics data. Celloscope outperformed other methods on simulated data, successfully indicated known brain structures and spatially distinguished between inhibitory and excitatory neuron types based in mouse brain tissue, and dissected large heterogeneity of immune infiltrate composition in prostate gland tissue.

bioinformatics↗