SigPrimedNet: A Signaling-Informed Neural Network for scRNA-seq Annotation of Known and Unknown Cell Types

Single-cell RNA sequencing is increasing our understanding of the behavior of complex tissues or organs, by providing unprecedented details on the complex cell type landscape at the level of individual cells. Cell type definition and functional annotation are key steps to understanding the molecular...

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Main Authors: Pelin Gundogdu, Inmaculada Alamo, Isabel A. Nepomuceno-Chamorro, Joaquin Dopazo, Carlos Loucera
Format: Article
Language:English
Published: MDPI AG 2023-04-01
Series:Biology
Subjects:
Online Access:https://www.mdpi.com/2079-7737/12/4/579
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author Pelin Gundogdu
Inmaculada Alamo
Isabel A. Nepomuceno-Chamorro
Joaquin Dopazo
Carlos Loucera
author_facet Pelin Gundogdu
Inmaculada Alamo
Isabel A. Nepomuceno-Chamorro
Joaquin Dopazo
Carlos Loucera
author_sort Pelin Gundogdu
collection DOAJ
description Single-cell RNA sequencing is increasing our understanding of the behavior of complex tissues or organs, by providing unprecedented details on the complex cell type landscape at the level of individual cells. Cell type definition and functional annotation are key steps to understanding the molecular processes behind the underlying cellular communication machinery. However, the exponential growth of scRNA-seq data has made the task of manually annotating cells unfeasible, due not only to an unparalleled resolution of the technology but to an ever-increasing heterogeneity of the data. Many supervised and unsupervised methods have been proposed to automatically annotate cells. Supervised approaches for cell-type annotation outperform unsupervised methods except when new (unknown) cell types are present. Here, we introduce SigPrimedNet an artificial neural network approach that leverages (i) efficient training by means of a sparsity-inducing signaling circuits-informed layer, (ii) feature representation learning through supervised training, and (iii) unknown cell-type identification by fitting an anomaly detection method on the learned representation. We show that SigPrimedNet can efficiently annotate known cell types while keeping a low false-positive rate for unseen cells across a set of publicly available datasets. In addition, the learned representation acts as a proxy for signaling circuit activity measurements, which provide useful estimations of the cell functionalities.
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spelling doaj.art-a12437f7fea94bb98ed71796197a76472023-11-17T18:24:13ZengMDPI AGBiology2079-77372023-04-0112457910.3390/biology12040579SigPrimedNet: A Signaling-Informed Neural Network for scRNA-seq Annotation of Known and Unknown Cell TypesPelin Gundogdu0Inmaculada Alamo1Isabel A. Nepomuceno-Chamorro2Joaquin Dopazo3Carlos Loucera4Computational Medicine Platform, Andalusian Public Foundation Progress and Health-FPS, 41013 Sevilla, SpainComputational Medicine Platform, Andalusian Public Foundation Progress and Health-FPS, 41013 Sevilla, SpainDpto. de Lenguajes y Sistemas Informáticos, Universidad de Sevilla, 41013 Seville, SpainComputational Medicine Platform, Andalusian Public Foundation Progress and Health-FPS, 41013 Sevilla, SpainComputational Medicine Platform, Andalusian Public Foundation Progress and Health-FPS, 41013 Sevilla, SpainSingle-cell RNA sequencing is increasing our understanding of the behavior of complex tissues or organs, by providing unprecedented details on the complex cell type landscape at the level of individual cells. Cell type definition and functional annotation are key steps to understanding the molecular processes behind the underlying cellular communication machinery. However, the exponential growth of scRNA-seq data has made the task of manually annotating cells unfeasible, due not only to an unparalleled resolution of the technology but to an ever-increasing heterogeneity of the data. Many supervised and unsupervised methods have been proposed to automatically annotate cells. Supervised approaches for cell-type annotation outperform unsupervised methods except when new (unknown) cell types are present. Here, we introduce SigPrimedNet an artificial neural network approach that leverages (i) efficient training by means of a sparsity-inducing signaling circuits-informed layer, (ii) feature representation learning through supervised training, and (iii) unknown cell-type identification by fitting an anomaly detection method on the learned representation. We show that SigPrimedNet can efficiently annotate known cell types while keeping a low false-positive rate for unseen cells across a set of publicly available datasets. In addition, the learned representation acts as a proxy for signaling circuit activity measurements, which provide useful estimations of the cell functionalities.https://www.mdpi.com/2079-7737/12/4/579scRNA-seqdeep learningexplainable artificial intelligencecell signalingcell-type identification
spellingShingle Pelin Gundogdu
Inmaculada Alamo
Isabel A. Nepomuceno-Chamorro
Joaquin Dopazo
Carlos Loucera
SigPrimedNet: A Signaling-Informed Neural Network for scRNA-seq Annotation of Known and Unknown Cell Types
Biology
scRNA-seq
deep learning
explainable artificial intelligence
cell signaling
cell-type identification
title SigPrimedNet: A Signaling-Informed Neural Network for scRNA-seq Annotation of Known and Unknown Cell Types
title_full SigPrimedNet: A Signaling-Informed Neural Network for scRNA-seq Annotation of Known and Unknown Cell Types
title_fullStr SigPrimedNet: A Signaling-Informed Neural Network for scRNA-seq Annotation of Known and Unknown Cell Types
title_full_unstemmed SigPrimedNet: A Signaling-Informed Neural Network for scRNA-seq Annotation of Known and Unknown Cell Types
title_short SigPrimedNet: A Signaling-Informed Neural Network for scRNA-seq Annotation of Known and Unknown Cell Types
title_sort sigprimednet a signaling informed neural network for scrna seq annotation of known and unknown cell types
topic scRNA-seq
deep learning
explainable artificial intelligence
cell signaling
cell-type identification
url https://www.mdpi.com/2079-7737/12/4/579
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