Alignment of Cell Lineage Trees Elucidates Genetic Programs for the Development and Evolution of Cell Types
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.
期刊:
iScience
2020
作者:
Jian-Rong Yang,Xiaoshu Chen,Xueqin Wang,Guifeng Zheng,Zizhang Li,Xiaoyu Zhang,Feng Chen,Xiaolong Cao,Jinghua Lin,Xujiang Yang,Meng Yuan
DOI:10.1016/j.isci.2020.101273
Computational comparison of developmental cell lineage trees by alignments
ABSTRACT The developmental cell lineage tree, which records every cell division event and the terminal developmental state of each single cell, is one of the most important traits of multicellular organisms, as well as key to many significant unresolved questions in biology. Recent technological breakthroughs are paving the way for direct determination of cell lineage trees, yet a general framework for the computational analysis of lineage trees, in particular an algorithm to compare two lineage trees, is still lacking. Based on previous findings that the same developmental program can be invoked by different cells on the lineage tree to produce highly similar subtrees, we designed D evelopmental C e ll L ineage T ree A lignment (DELTA), an algorithm that exhaustively searches for lineage trees with phenotypic resemblance in lineal organization of terminal cells, meanwhile resolving detailed correspondence between individual cells. Using simulated and nematode lineage trees, we demonstrated DELTA’s capability of revealing similarities of developmental programs by lineal resemblances. Moreover, DELTA successfully identifies gene deletion-triggered homeotic cell fate transformations, reveals functional relationship between mutants by quantifying their lineal similarities, and finds the evolutionary correspondence between cell types defined non-uniformly for different species. DELTA establishes novel foundation for comparative study of lineage trees, much like sequence alignment algorithm for biological sequences, and along with the increase of lineage tree data, will likely bring unique insights for the myriads of important questions surrounding cell lineage trees.
期刊:
bioRxiv
2019
作者:
Jian-Rong Yang,Xiaoshu Chen,Xueqin Wang,Guifeng Zheng,Zizhang Li,Xiaoyu Zhang,Feng Chen,Xiaolong Cao,Jinghua Lin,Xujiang Yang,Meng Yuan
DOI:10.1101/577809
