scInterpreter: a knowledge-regularized generative model for interpretably integrating scRNA-seq data

Abstract Background The rapid emergence of single-cell RNA-seq (scRNA-seq) data presents remarkable opportunities for broad investigations through integration analyses. However, most integration models are black boxes that lack interpretability or are hard to train. Results To address the above issu...

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Main Authors: Zhen-Hao Guo, Yan Wu, Siguo Wang, Qinhu Zhang, Jin-Ming Shi, Yan-Bin Wang, Zhan-Heng Chen
Format: Article
Language:English
Published: BMC 2023-12-01
Series:BMC Bioinformatics
Subjects:
Online Access:https://doi.org/10.1186/s12859-023-05579-4
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author Zhen-Hao Guo
Yan Wu
Siguo Wang
Qinhu Zhang
Jin-Ming Shi
Yan-Bin Wang
Zhan-Heng Chen
author_facet Zhen-Hao Guo
Yan Wu
Siguo Wang
Qinhu Zhang
Jin-Ming Shi
Yan-Bin Wang
Zhan-Heng Chen
author_sort Zhen-Hao Guo
collection DOAJ
description Abstract Background The rapid emergence of single-cell RNA-seq (scRNA-seq) data presents remarkable opportunities for broad investigations through integration analyses. However, most integration models are black boxes that lack interpretability or are hard to train. Results To address the above issues, we propose scInterpreter, a deep learning-based interpretable model. scInterpreter substantially outperforms other state-of-the-art (SOTA) models in multiple benchmark datasets. In addition, scInterpreter is extensible and can integrate and annotate atlas scRNA-seq data. We evaluated the robustness of scInterpreter in a variety of situations. Through comparison experiments, we found that with a knowledge prior, the training process can be significantly accelerated. Finally, we conducted interpretability analysis for each dimension (pathway) of cell representation in the embedding space. Conclusions The results showed that the cell representations obtained by scInterpreter are full of biological significance. Through weight sorting, we found several new genes related to pathways in PBMC dataset. In general, scInterpreter is an effective and interpretable integration tool. It is expected that scInterpreter will bring great convenience to the study of single-cell transcriptomics.
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spelling doaj.art-4b1520acd296408fa75366a0387eae142023-12-17T12:31:51ZengBMCBMC Bioinformatics1471-21052023-12-0124111410.1186/s12859-023-05579-4scInterpreter: a knowledge-regularized generative model for interpretably integrating scRNA-seq dataZhen-Hao Guo0Yan Wu1Siguo Wang2Qinhu Zhang3Jin-Ming Shi4Yan-Bin Wang5Zhan-Heng Chen6College of Electronics and Information Engineering, Tongji UniversityCollege of Electronics and Information Engineering, Tongji UniversityEIT Institute for Advanced StudyEIT Institute for Advanced StudyDepartment of Endocrinology, Aviation General HospitalCollege of Computer Science and Technology, Zhejiang UniversityDepartment of Clinical Anesthesiology, Faculty of Anesthesiology, Second Military Medical University / Naval Medical UniversityAbstract Background The rapid emergence of single-cell RNA-seq (scRNA-seq) data presents remarkable opportunities for broad investigations through integration analyses. However, most integration models are black boxes that lack interpretability or are hard to train. Results To address the above issues, we propose scInterpreter, a deep learning-based interpretable model. scInterpreter substantially outperforms other state-of-the-art (SOTA) models in multiple benchmark datasets. In addition, scInterpreter is extensible and can integrate and annotate atlas scRNA-seq data. We evaluated the robustness of scInterpreter in a variety of situations. Through comparison experiments, we found that with a knowledge prior, the training process can be significantly accelerated. Finally, we conducted interpretability analysis for each dimension (pathway) of cell representation in the embedding space. Conclusions The results showed that the cell representations obtained by scInterpreter are full of biological significance. Through weight sorting, we found several new genes related to pathways in PBMC dataset. In general, scInterpreter is an effective and interpretable integration tool. It is expected that scInterpreter will bring great convenience to the study of single-cell transcriptomics.https://doi.org/10.1186/s12859-023-05579-4Single-cell RNA-seqBatch correctionIntegrationDeep learningKnowledge-regularized
spellingShingle Zhen-Hao Guo
Yan Wu
Siguo Wang
Qinhu Zhang
Jin-Ming Shi
Yan-Bin Wang
Zhan-Heng Chen
scInterpreter: a knowledge-regularized generative model for interpretably integrating scRNA-seq data
BMC Bioinformatics
Single-cell RNA-seq
Batch correction
Integration
Deep learning
Knowledge-regularized
title scInterpreter: a knowledge-regularized generative model for interpretably integrating scRNA-seq data
title_full scInterpreter: a knowledge-regularized generative model for interpretably integrating scRNA-seq data
title_fullStr scInterpreter: a knowledge-regularized generative model for interpretably integrating scRNA-seq data
title_full_unstemmed scInterpreter: a knowledge-regularized generative model for interpretably integrating scRNA-seq data
title_short scInterpreter: a knowledge-regularized generative model for interpretably integrating scRNA-seq data
title_sort scinterpreter a knowledge regularized generative model for interpretably integrating scrna seq data
topic Single-cell RNA-seq
Batch correction
Integration
Deep learning
Knowledge-regularized
url https://doi.org/10.1186/s12859-023-05579-4
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