C. elegans exhibits coordinated oscillation in gene activation in single-cell developmental data

Abstract

BackgroundThe advent of in vivo automated single-cell lineaging and sequencing will dramatically increase our understanding of development. New integrative analysis techniques are needed to generate insights from single-cell developmental data.\n\nResultsWe applied novel meta-analysis techniques to the EPIC single-cell-resolution developmental gene expression dataset for C. elegans to show that a simple linear combination of the expression levels of the developmental genes is strongly correlated with the developmental age of the organism, irrespective of the cell division rate of different cell lineages. We uncovered a pattern of collective sinusoidal oscillation in gene activation, in multiple dominant frequencies and in multiple orthogonal axes of gene expression, pointing to the existence of a coordinated, multi-frequency global timing mechanism. We developed a novel method based on Fishers Discriminant Analysis (FDA) to identify linear gene expression weightings that are able to produce sinusoidal oscillations of any frequency and phase, adding to the evidence that oscillatory mechanisms likely play an important role in the timing of development. We cross-linked EPIC with gene ontology and anatomy ontology terms, employing FDA methods to identify previously unknown positive and negative genetic contributions to developmental processes and cell phenotypes.\n\nConclusionsThis meta-analysis demonstrates new evidence for direct linear and/or sinusoidal mechanisms regulating the timing of development. We uncovered a number of previously unknown positive and negative correlations between developmental genes and developmental processes or cell phenotypes. The presented novel analysis techniques are broadly applicable within developmental biology.