Contrastive latent variable modeling with application to case-control sequencing experiments

DOI10.1214/21-AOAS1534zbMATH Open1498.62228arXiv2102.06731OpenAlexW3131858063MaRDI QIDQ2170381FDOQ2170381

Yanyan Li

Publication date: 5 September 2022

Published in: The Annals of Applied Statistics (Search for Journal in Brave)

Abstract: High-throughput RNA-sequencing (RNA-seq) technologies are powerful tools for understanding cellular state. Often it is of interest to quantify and summarize changes in cell state that occur between experimental or biological conditions. Differential expression is typically assessed using univariate tests to measure gene-wise shifts in expression. However, these methods largely ignore changes in transcriptional correlation. Furthermore, there is a need to identify the low-dimensional structure of the gene expression shift to identify collections of genes that change between conditions. Here, we propose contrastive latent variable models designed for count data to create a richer portrait of differential expression in sequencing data. These models disentangle the sources of transcriptional variation in different conditions, in the context of an explicit model of variation at baseline. Moreover, we develop a model-based hypothesis testing framework that can test for global and gene subset-specific changes in expression. We test our model through extensive simulations and analyses with count-based gene expression data from perturbation and observational sequencing experiments. We find that our methods can effectively summarize and quantify complex transcriptional changes in case-control experimental sequencing data.

Full work available at URL: https://arxiv.org/abs/2102.06731

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zbMATH Keywords

latent variable modelsdifferential expressioncase-control dataRNA sequencingcontrastive models

Mathematics Subject Classification ID

Applications of statistics to biology and medical sciences; meta analysis (62P10) Hypothesis testing in multivariate analysis (62H15)

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Uses Software

• edgeR
• TensorFlow
• MAST
• splatter

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