Leveraging spatial transcriptomics data to recover cell locations in single-cell RNA-seq with CeLEry

Abstract Single-cell RNA sequencing (scRNA-seq) has revolutionized our understanding of cellular heterogeneity in health and disease. However, the lack of physical relationships among dissociated cells has limited its applications. To address this issue, we present CeLEry (Cell Location recovEry), a...

Full description

Bibliographic Details
Main Authors: Qihuang Zhang, Shunzhou Jiang, Amelia Schroeder, Jian Hu, Kejie Li, Baohong Zhang, David Dai, Edward B. Lee, Rui Xiao, Mingyao Li
Format: Article
Language:English
Published: Nature Portfolio 2023-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-39895-3
_version_ 1797784541778149376
author Qihuang Zhang
Shunzhou Jiang
Amelia Schroeder
Jian Hu
Kejie Li
Baohong Zhang
David Dai
Edward B. Lee
Rui Xiao
Mingyao Li
author_facet Qihuang Zhang
Shunzhou Jiang
Amelia Schroeder
Jian Hu
Kejie Li
Baohong Zhang
David Dai
Edward B. Lee
Rui Xiao
Mingyao Li
author_sort Qihuang Zhang
collection DOAJ
description Abstract Single-cell RNA sequencing (scRNA-seq) has revolutionized our understanding of cellular heterogeneity in health and disease. However, the lack of physical relationships among dissociated cells has limited its applications. To address this issue, we present CeLEry (Cell Location recovEry), a supervised deep learning algorithm that leverages gene expression and spatial location relationships learned from spatial transcriptomics to recover the spatial origins of cells in scRNA-seq. CeLEry has an optional data augmentation procedure via a variational autoencoder, which improves the method’s robustness and allows it to overcome noise in scRNA-seq data. We show that CeLEry can infer the spatial origins of cells in scRNA-seq at multiple levels, including 2D location and spatial domain of a cell, while also providing uncertainty estimates for the recovered locations. Our comprehensive benchmarking evaluations on multiple datasets generated from brain and cancer tissues using Visium, MERSCOPE, MERFISH, and Xenium demonstrate that CeLEry can reliably recover the spatial location information for cells using scRNA-seq data.
first_indexed 2024-03-13T00:41:23Z
format Article
id doaj.art-211cff1dc45b4b52ab015e67533383d8
institution Directory Open Access Journal
issn 2041-1723
language English
last_indexed 2024-03-13T00:41:23Z
publishDate 2023-07-01
publisher Nature Portfolio
record_format Article
series Nature Communications
spelling doaj.art-211cff1dc45b4b52ab015e67533383d82023-07-09T11:17:39ZengNature PortfolioNature Communications2041-17232023-07-0114111910.1038/s41467-023-39895-3Leveraging spatial transcriptomics data to recover cell locations in single-cell RNA-seq with CeLEryQihuang Zhang0Shunzhou Jiang1Amelia Schroeder2Jian Hu3Kejie Li4Baohong Zhang5David Dai6Edward B. Lee7Rui Xiao8Mingyao Li9Department of Epidemiology, Biostatistics and Occupational Health, School of Population and Global Health, McGill UniversityStatistical Center for Single-Cell and Spatial Genomics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of PennsylvaniaStatistical Center for Single-Cell and Spatial Genomics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of PennsylvaniaDepartment of Human Genetics, School of Medicine, Emory UniversityResearch Department, Biogen, Inc.Research Department, Biogen, Inc.Translational Neuropathology Research Laboratory, Department of Pathology and Laboratory Medicine, University of PennsylvaniaTranslational Neuropathology Research Laboratory, Department of Pathology and Laboratory Medicine, University of PennsylvaniaStatistical Center for Single-Cell and Spatial Genomics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of PennsylvaniaStatistical Center for Single-Cell and Spatial Genomics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of PennsylvaniaAbstract Single-cell RNA sequencing (scRNA-seq) has revolutionized our understanding of cellular heterogeneity in health and disease. However, the lack of physical relationships among dissociated cells has limited its applications. To address this issue, we present CeLEry (Cell Location recovEry), a supervised deep learning algorithm that leverages gene expression and spatial location relationships learned from spatial transcriptomics to recover the spatial origins of cells in scRNA-seq. CeLEry has an optional data augmentation procedure via a variational autoencoder, which improves the method’s robustness and allows it to overcome noise in scRNA-seq data. We show that CeLEry can infer the spatial origins of cells in scRNA-seq at multiple levels, including 2D location and spatial domain of a cell, while also providing uncertainty estimates for the recovered locations. Our comprehensive benchmarking evaluations on multiple datasets generated from brain and cancer tissues using Visium, MERSCOPE, MERFISH, and Xenium demonstrate that CeLEry can reliably recover the spatial location information for cells using scRNA-seq data.https://doi.org/10.1038/s41467-023-39895-3
spellingShingle Qihuang Zhang
Shunzhou Jiang
Amelia Schroeder
Jian Hu
Kejie Li
Baohong Zhang
David Dai
Edward B. Lee
Rui Xiao
Mingyao Li
Leveraging spatial transcriptomics data to recover cell locations in single-cell RNA-seq with CeLEry
Nature Communications
title Leveraging spatial transcriptomics data to recover cell locations in single-cell RNA-seq with CeLEry
title_full Leveraging spatial transcriptomics data to recover cell locations in single-cell RNA-seq with CeLEry
title_fullStr Leveraging spatial transcriptomics data to recover cell locations in single-cell RNA-seq with CeLEry
title_full_unstemmed Leveraging spatial transcriptomics data to recover cell locations in single-cell RNA-seq with CeLEry
title_short Leveraging spatial transcriptomics data to recover cell locations in single-cell RNA-seq with CeLEry
title_sort leveraging spatial transcriptomics data to recover cell locations in single cell rna seq with celery
url https://doi.org/10.1038/s41467-023-39895-3
work_keys_str_mv AT qihuangzhang leveragingspatialtranscriptomicsdatatorecovercelllocationsinsinglecellrnaseqwithcelery
AT shunzhoujiang leveragingspatialtranscriptomicsdatatorecovercelllocationsinsinglecellrnaseqwithcelery
AT ameliaschroeder leveragingspatialtranscriptomicsdatatorecovercelllocationsinsinglecellrnaseqwithcelery
AT jianhu leveragingspatialtranscriptomicsdatatorecovercelllocationsinsinglecellrnaseqwithcelery
AT kejieli leveragingspatialtranscriptomicsdatatorecovercelllocationsinsinglecellrnaseqwithcelery
AT baohongzhang leveragingspatialtranscriptomicsdatatorecovercelllocationsinsinglecellrnaseqwithcelery
AT daviddai leveragingspatialtranscriptomicsdatatorecovercelllocationsinsinglecellrnaseqwithcelery
AT edwardblee leveragingspatialtranscriptomicsdatatorecovercelllocationsinsinglecellrnaseqwithcelery
AT ruixiao leveragingspatialtranscriptomicsdatatorecovercelllocationsinsinglecellrnaseqwithcelery
AT mingyaoli leveragingspatialtranscriptomicsdatatorecovercelllocationsinsinglecellrnaseqwithcelery