May 24, 2019

Decomposing Cell Identity for Transfer Learning across Cellular Measurements, Platforms, Tissues, and Species

Cell Systems
Genevieve L Stein-O'BrienElana J. Fertig

Abstract

Analysis of gene expression in single cells allows for decomposition of cellular states as low-dimensional latent spaces. However, the interpretation and validation of these spaces remains a challenge. Here, we present scCoGAPS, which defines latent spaces from a source single-cell RNA-sequencing (scRNA-seq) dataset, and projectR, which evaluates these latent spaces in independent target datasets via transfer learning. Application of developing mouse retina to scRNA-Seq reveals intrinsic relationships across biological contexts and assays while avoiding batch effects and other technical features. We compare the dimensions learned in this source dataset to adult mouse retina, a time-course of human retinal development, select scRNA-seq datasets from developing brain, chromatin accessibility data, and a murine-cell type atlas to identify shared biological features. These tools lay the groundwork for exploratory analysis of scRNA-seq data via latent space representations, enabling a shift in how we compare and identify cells beyond reliance on marker genes or ensemble molecular identity.

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Mentioned in this Paper

Brain
Retinal Diseases
Sequence Determinations
Anatomical Space Structure
Gene Expression
Cellularization
RNA, Small Cytoplasmic
Species
Analysis
Chromatin

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