title: Time-variant clustering model for understanding cell fate decisions.
abstract: Both spatial characteristics and temporal features are often the subjects of concern in physical, social, and biological studies. This work tackles the clustering problems for time course data in which the cluster number and clustering structure change with respect to time, dubbed time-variant clustering. We developed a hierarchical model that simultaneously clusters the objects at every time point and describes the relationships of the clusters between time points. The hidden layer of this model is a generalized form of branching processes. A reversible-jump Markov Chain Monte Carlo method was implemented for model inference, and a feature selection procedure was developed. We applied this method to explore an open question in preimplantation embryonic development. Our analyses using single-cell gene expression data suggested that the earliest cell fate decision could start at the 4-cell stage in mice, earlier than the commonly thought 8- to 16-cell stage. These results together with independent experimental data from single-cell RNA-seq provided support against a prevailing hypothesis in mammalian development.
authors.affiliation: Department of Statistics, Key Laboratory for Applied Statistics of the Ministry of Education, and School of Mathematics and Statistics, Northeast Normal University, Changchun 130024, China; and.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Bioengineering, University of California, San Diego, CA 92093.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Bioengineering, University of California, San Diego, CA 92093.
authors.forename: Fernando H
authors.initials: FH
authors.lastname: Biase
authors.affiliation: Department of Bioengineering, University of California, San Diego, CA 92093.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Yu
authors.affiliation: Department of Bioengineering, University of California, San Diego, CA 92093 szhong@ucsd.edu.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhong
mesh_terms: D000818:Animals; D001757:Blastomeres / Q000166:cytology / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology*; D047108:Embryonic Development / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008954:Models, Biological
keywords: branching process; cell fate; clustering; embryonic development; time