Detecting retinal neural and stromal cell classes and ganglion cell subtypes based on transcriptome data with deep transfer learning

Author:

Madadi Yeganeh12,Sun Jian1,Chen Hao3,Williams Robert4,Yousefi Siamak14ORCID

Affiliation:

1. Department of Ophthalmology, University of Tennessee Health Science Center , Memphis, TN, USA

2. University of Tehran , Tehran, Iran

3. Department of Pharmacology, Addiction Science and Toxicology, University of Tennessee Health Science Center , Memphis, TN, USA

4. Department of Genetics and Informatics, University of Tennessee Health Science Center , Memphis, TN, USA

Abstract

Abstract Motivation To develop and assess the accuracy of deep learning models that identify different retinal cell types, as well as different retinal ganglion cell (RGC) subtypes, based on patterns of single-cell RNA sequencing (scRNA-seq) in multiple datasets. Results Deep domain adaptation models were developed and tested using three different datasets. The first dataset included 44 808 single retinal cells from mice (39 cell types) with 24 658 genes, the second dataset included 6225 single RGCs from mice (41 subtypes) with 13 616 genes and the third dataset included 35 699 single RGCs from mice (45 subtypes) with 18 222 genes. We used four loss functions in the learning process to align the source and target distributions, reduce misclassification errors and maximize robustness. Models were evaluated based on classification accuracy and confusion matrix. The accuracy of the model for correctly classifying 39 different retinal cell types in the first dataset was ∼92%. Accuracy in the second and third datasets reached ∼97% and 97% in correctly classifying 40 and 45 different RGCs subtypes, respectively. Across a range of seven different batches in the first dataset, the accuracy of the lead model ranged from 74% to nearly 100%. The lead model provided high accuracy in identifying retinal cell types and RGC subtypes based on scRNA-seq data. The performance was reasonable based on data from different batches as well. The validated model could be readily applied to scRNA-seq data to identify different retinal cell types and subtypes. Availability and implementation The code and datasets are available on https://github.com/DM2LL/Detecting-Retinal-Cell-Classes-and-Ganglion-Cell-Subtypes. We have also added the class labels of all samples to the datasets. Supplementary information Supplementary data are available at Bioinformatics online.

Funder

Bright Focus Foundation

Research to Prevent Blindness

Publisher

Oxford University Press (OUP)

Subject

Computational Mathematics,Computational Theory and Mathematics,Computer Science Applications,Molecular Biology,Biochemistry,Statistics and Probability

Reference39 articles.

1. scPred: accurate supervised method for cell-type classification from single-cell RNA-seq data;Alquicira-Hernandez;Genome Biol,2019

2. Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage;Aran;Nat. Immunol,2019

3. Integrating single-cell transcriptomic data across different conditions, technologies, and species;Butler;Nat. Biotechnol,2018

4. Searching large-scale scRNA-seq databases via unbiased cell embedding with cell BLAST;Cao;Nat. Commun,2020

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