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Leveraging neighborhood representations of single-cell data to achieve sensitive DE testing with miloDE

Alsu Missarova, Emma Dann, Leah Rosen, Rahul Satija, John C. Marioni

2024Genome biology21 citationsDOIOpen Access PDF

Abstract

Single-cell RNA-sequencing enables testing for differential expression (DE) between conditions at a cell type level. While powerful, one of the limitations of such approaches is that the sensitivity of DE testing is dictated by the sensitivity of clustering, which is often suboptimal. To overcome this, we present miloDE-a cluster-free framework for DE testing (available as an open-source R package). We illustrate the performance of miloDE on both simulated and real data. Using miloDE, we identify a transient hemogenic endothelia-like state in mouse embryos lacking Tal1 and detect distinct programs during macrophage activation in idiopathic pulmonary fibrosis.

Topics & Concepts

BiologyComputational biologyCluster analysisSingle-cell analysisSensitivity (control systems)R packageHuman geneticsCluster (spacecraft)Cell typeCellComputer scienceGeneticsMachine learningGeneElectronic engineeringComputational scienceEngineeringProgramming languageSingle-cell and spatial transcriptomicsRenal and related cancersExtracellular vesicles in disease
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