FitDevo: accurate inference of single-cell developmental potential using sample-specific gene weight

Author:

Zhang Feng12ORCID,Yang Chen12,Wang Yihao34567,Jiao Huiyuan12,Wang Zhiming12,Shen Jianfeng34567,Li Lingjie12

Affiliation:

1. Department of Histoembryology , Genetics and Developmental Biology, Shanghai Key Laboratory of Reproductive Medicine, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, , Shanghai 200025 , China

2. Shanghai Jiao Tong University School of Medicine , Genetics and Developmental Biology, Shanghai Key Laboratory of Reproductive Medicine, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, , Shanghai 200025 , China

3. Department of Ophthalmology , Ninth People’s Hospital, , Shanghai 200025 , China

4. Shanghai Jiao Tong University School of Medicine , Ninth People’s Hospital, , Shanghai 200025 , China

5. Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology , Shanghai 200025 , China

6. Institute of Translational Medicine , National Facility for Translational Medicine, , Shanghai 201109 , China

7. Shanghai Jiao Tong University , National Facility for Translational Medicine, , Shanghai 201109 , China

Abstract

Abstract The quantification of developmental potential is critical for determining developmental stages and identifying essential molecular signatures in single-cell studies. Here, we present FitDevo, a novel method for inferring developmental potential using scRNA-seq data. The main idea of FitDevo is first to generate sample-specific gene weight (SSGW) and then infer developmental potential by calculating the correlation between SSGW and gene expression. SSGW is generated using a generalized linear model that combines sample-specific information and gene weight learned from a training dataset covering scRNA-seq data of 17 previously published datasets. We have rigorously validated FitDevo’s effectiveness using a testing dataset with scRNA-seq data from 28 existing datasets and have also demonstrated its superiority over current methods. Furthermore, FitDevo’s broad application scope has been illustrated using three practical scenarios: deconvolution analysis of epidermis, spatial transcriptomic data analysis of hearts and intestines, and developmental potential analysis of breast cancer. The source code and related data are available at https://github.com/jumphone/fitdevo.

Funder

National Natural Science Foundation of China

National Key Research and Development Program of China

Shanghai Sailing Program

Natural Science Foundation of Shanghai

Program for Oriental Scholars of Shanghai Universities

Startup Fund for Young Faculty at SJTU

Shanghai Collaborative Innovation Center of Cellular Homeostasis Regulation and Human Disease

Publisher

Oxford University Press (OUP)

Subject

Molecular Biology,Information Systems

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