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Zhuohan Yu

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AAAI Conference 2023 Conference Paper

Unsupervised Deep Embedded Fusion Representation of Single-Cell Transcriptomics

Yue Cheng
Yanchi Su
Zhuohan Yu
Yanchun Liang
Ka-Chun Wong
Xiangtao Li

Cell clustering is a critical step in analyzing single-cell RNA sequencing (scRNA-seq) data, which allows us to characterize the cellular heterogeneity of transcriptional profiling at the single-cell level. Single-cell deep embedded representation models have recently become popular since they can learn feature representation and clustering simultaneously. However, the model still suffers from a variety of significant challenges, including the massive amount of data, pervasive dropout events, and complicated noise patterns in transcriptional profiling. Here, we propose a Single-Cell Deep Embedding Fusion Representation (scDEFR) model, which develop a deep embedded fusion representation to learn fused heterogeneous latent embedding that contains both the transcriptome gene-level information and the cell topology information. We first fuse them layer by layer to obtain compressed representations of intercellular relationships and transcriptome information. After that, the zero-inflated negative binomial model (ZINB)-based decoder is proposed to capture the global probabilistic structure of the data and reconstruct the final gene expression information and cell graph. Finally, by simultaneously integrating the clustering loss, crossentropy loss, ZINB loss, and the cell graph reconstruction loss, scDEFR can optimize clustering performance and learn the latent representation in fused information under a joint mutual supervised strategy. We conducted extensive and comprehensive experiments on 15 single-cell RNA-seq datasets from different sequencing platforms to demonstrate the superiority of scDEFR over a variety of state-of-the-art methods.

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AAAI Conference 2022 Conference Paper

ZINB-Based Graph Embedding Autoencoder for Single-Cell RNA-Seq Interpretations

Zhuohan Yu
Yifu Lu
Yunhe Wang
Fan Tang
Ka-Chun Wong
Xiangtao Li

Single-cell RNA sequencing (scRNA-seq) provides high-throughput information about the genome-wide gene expression levels at the single-cell resolution, bringing a precise understanding on the transcriptome of individual cells. Unfortunately, the rapidly growing scRNA-seq data and the prevalence of dropout events pose substantial challenges for cell type annotation. Here, we propose a single-cell model-based deep graph embedding clustering (scTAG) method, which simultaneously learns cell–cell topology representations and identifies cell clusters based on deep graph convolutional network. scTAG integrates the zero-inflated negative binomial (ZINB) model into a topology adaptive graph convolutional autoencoder to learn the lowdimensional latent representation and adopts Kullback–Leibler (KL) divergence for the clustering tasks. By simultaneously optimizing the clustering loss, ZINB loss, and the cell graph reconstruction loss, scTAG jointly optimizes cluster label assignment and feature learning with the topological structures preserved in an end-to-end manner. Extensive experiments on 16 single-cell RNA-seq datasets from diverse yet representative single-cell sequencing platforms demonstrate the superiority of scTAG over various state-of-the-art clustering methods.

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