Integrating single-cell multimodal epigenomic data using 1D convolutional neural networks

Recent experimental developments enable single-cell multimodal epigenomic profiling, which measures multiple histone modifications and chromatin accessibility within the same cell. Such parallel measurements provide exciting new opportunities to investigate how epigenomic modalities vary together across cell types and states. A pivotal step in using these types of data is integrating the epigenomic modalities to learn a unified representation of each cell, but existing approaches are not designed to model the unique nature of this data type. Our key insight is to model single-cell multimodal epigenome data as a multichannel sequential signal.

We developed ConvNet-VAEs, a novel framework that uses one-dimensional (1D) convolutional variational autoencoders (VAEs) for single-cell multimodal epigenomic data integration. We evaluated ConvNet-VAEs on nano-CUT&Tag and single-cell nanobody-tethered transposition followed by sequencing data generated from juvenile mouse brain and human bone marrow. We found that ConvNet-VAEs can perform dimension reduction and batch correction better than previous architectures while using significantly fewer parameters. Furthermore, the performance gap between convolutional and fully connected architectures increases with the number of modalities, and deeper convolutional architectures can increase the performance, while the performance degrades for deeper fully connected architectures. Our results indicate that convolutional autoencoders are a promising method for integrating current and future single-cell multimodal epigenomic datasets.

The source code of VAE models and a demo in Jupyter notebook are available at https://github.com/welch-lab/ConvNetVAE.