Factorized Discriminant Analysis for Genetic Signatures of Neuronal Phenotypes

TL;DR

This paper introduces factorized linear discriminant analysis (FLDA), a new method for linear dimensionality reduction that identifies gene expression features correlated with phenotypes, enhancing interpretability and gene selection in single-cell transcriptomic data.

Contribution

The paper proposes FLDA, a novel linear discriminant analysis method combined with sparsity regularization, specifically designed for interpretability and gene selection in high-dimensional biological data.

Findings

FLDA effectively captures structural patterns aligned with phenotypic features.

FLDA uncovers key genes associated with specific neuronal phenotypes.

Application to Drosophila neuron data demonstrates improved interpretability.

Abstract

Navigating the complex landscape of single-cell transcriptomic data presents significant challenges. Central to this challenge is the identification of a meaningful representation of high-dimensional gene expression patterns that sheds light on the structural and functional properties of cell types. Pursuing model interpretability and computational simplicity, we often look for a linear transformation of the original data that aligns with key phenotypic features of cells. In response to this need, we introduce factorized linear discriminant analysis (FLDA), a novel method for linear dimensionality reduction. The crux of FLDA lies in identifying a linear function of gene expression levels that is highly correlated with one phenotypic feature while minimizing the influence of others. To augment this method, we integrate it with a sparsity-based regularization algorithm. This integration is crucial as it selects a subset of genes pivotal to a specific phenotypic feature or a combination thereof. To illustrate the effectiveness of FLDA, we apply it to transcriptomic datasets from neurons in the Drosophila optic lobe. We demonstrate that FLDA not only captures the inherent structural patterns aligned with phenotypic features but also uncovers key genes associated with each phenotype.