Publication

A maximum-likelihood approach for building cell-type trees by lifting

Résumé

Background: In cell differentiation, a less specialized cell differentiates into a more specialized one, even though all cells in one organism have (almost) the same genome. Epigenetic factors such as histone modifications are known to play a significant role in cell differentiation. We previously introduce cell-type trees to represent the differentiation of cells into more specialized types, a representation that partakes of both ontogeny and phylogeny. Results: We propose a maximum-likelihood (ML) approach to build cell-type trees and show that this ML approach outperforms our earlier distance-based and parsimony-based approaches. We then study the reconstruction of ancestral cell types; since both ancestral and derived cell types can coexist in adult organisms, we propose a lifting algorithm to infer internal nodes. We present results on our lifting algorithm obtained both through simulations and on real datasets. Conclusions: We show that our ML-based approach outperforms previously proposed techniques such as distance-based and parsimony-based methods. We show our lifting-based approach works well on both simulated and real data.

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Concepts associés (36)
Cell type
A cell type is a classification used to identify cells that share morphological or phenotypical features. A multicellular organism may contain cells of a number of widely differing and specialized cell types, such as muscle cells and skin cells, that differ both in appearance and function yet have identical genomic sequences. Cells may have the same genotype, but belong to different cell types due to the differential regulation of the genes they contain.
Maximum de parcimonie
Les méthodes de maximum de parcimonie, ou plus simplement méthodes de parcimonie ou encore parcimonie de Wagner, sont une méthode statistique non-paramétrique très utilisée, notamment pour l'inférence phylogénétique. Cette méthode permet de construire des arbres de classification hiérarchique après enracinement, lesquels permettent d'obtenir des informations sur la structure de parenté d'un ensemble de taxons. Sous l'hypothèse du maximum de parcimonie, l'arbre phylogénétique « préféré » est celui qui requiert le plus petit nombre de changements évolutifs.
Différenciation cellulaire
La différenciation cellulaire est un concept de biologie du développement décrivant le processus par lequel les cellules se spécialisent en un « type » cellulaire avec une structure et une composition spécifiques permettant d'accomplir une ou plusieurs fonctions particulières. La morphologie d'une cellule peut changer radicalement durant la différenciation, mais le matériel génétique reste le même, à quelques exceptions près. Une cellule capable de se différencier en plusieurs types de cellules est appelée pluripotente.
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