Alignment of Cell Lineage Trees Elucidates Genetic Programs for the Development and Evolution of Cell Types
Meng Yuan,
Xujiang Yang,
Jinghua Lin,
Xiaolong Cao,
Feng Chen,
Xiaoyu Zhang,
Zizhang Li,
Guifeng Zheng,
Xueqin Wang,
Xiaoshu Chen,
Jian-Rong Yang
Affiliations
Meng Yuan
Department of Biomedical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
Xujiang Yang
Department of Biomedical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
Jinghua Lin
School of Data and Computer Science, Sun Yat-sen University, Guangzhou 510275, China
Xiaolong Cao
Department of Biomedical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
Feng Chen
Department of Biomedical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
Xiaoyu Zhang
Department of Biomedical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
Zizhang Li
Department of Biomedical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
Guifeng Zheng
School of Data and Computer Science, Sun Yat-sen University, Guangzhou 510275, China
Xueqin Wang
Department of Statistics and Finance, School of Management, University of Science and Technology of China, Hefei 230026, China
Xiaoshu Chen
Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Corresponding author
Jian-Rong Yang
Department of Biomedical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; RNA Biomedical Institute, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China; Corresponding author
Summary: A full understanding of the developmental process requires fine-scale characterization of cell divisions and cell types, which are naturally organized as the developmental cell lineage tree (CLT). Technological breakthroughs facilitated determination of more CLTs, but complete comprehension of the data remains difficult without quantitative comparison among CLTs. We hereby quantified phenotypic similarity between CLTs using a novel computational method that exhaustively searches for optimal correspondence between individual cells meanwhile retaining their topological relationships. The revealed CLT similarities allowed us to infer functional similarity at the transcriptome level, identify cell fate transformations, predict functional relationships between mutants, and find evolutionary correspondence between cell types of different species. By allowing quantitative comparison between CLTs, our work is expected to greatly enhance the interpretability of relevant data and help answer the myriad of questions surrounding the developmental process.
