ChroMo, an Application for Unsupervised Analysis of Chromosome Movements in Meiosis.

Daniel León-Periñán,Alfonso Fernández-Álvarez

doi:10.3390/cells10082013

Abstract

Nuclear movements during meiotic prophase, driven by cytoskeleton forces, are a broadly conserved mechanism in opisthokonts and plants to promote pairing between homologous chromosomes. These forces are transmitted to the chromosomes by specific associations between telomeres and the nuclear envelope during meiotic prophase. Defective chromosome movements (CMs) harm pairing and recombination dynamics between homologues, thereby affecting faithful gametogenesis. For this reason, modelling the behaviour of CMs and their possible microvariations as a result of mutations or physico-chemical stress is important to understand this crucial stage of meiosis. Current developments in high-throughput imaging and image processing are yielding large CM datasets that are suitable for data mining approaches. To facilitate adoption of data mining pipelines, we present ChroMo, an interactive, unsupervised cloud application specifically designed for exploring CM datasets from live imaging. ChroMo contains a wide selection of algorithms and visualizations for time-series segmentation, motif discovery, and assessment of causality networks. Using ChroMo to analyse meiotic CMs in fission yeast, we found previously undiscovered features of CMs and causality relationships between chromosome morphology and trajectory. ChroMo will be a useful tool for understanding the behaviour of meiotic CMs in yeast and other model organisms.

Highlights

Meiosis is an essential process for promoting genetic diversity that allows for the generation of new allelic combinations
We have developed the open-source web application ChroMo as a precise and unsupervised method for exploring meiotic chromosome movements (CMs) from live-imaging data to find patterns, microvariations, and causal relations
ChroMo was initially designed to explore the CMs during meiotic prophase in fission yeast, but it supports other types of movement and organisms, as well as other meiotic stages, for instance, the two rounds of chromosome segregations in meiosis I (MI) and meiosis II (MII)

Summary

Introduction

Meiosis is an essential process for promoting genetic diversity that allows for the generation of new allelic combinations. The critical stage for safeguarding genetic diversity is the recombination between homologous chromosomes during meiotic prophase. Homologous chromosome search is facilitated by nuclear movements that are driven by cytoskeleton forces [5,6,7]. Nuclear movements are transmitted to the chromosomes by the formation of the telomere bouquet, a conserved chromosomal configuration in which the telomeres cluster together in a specific region of the nuclear envelope (NE), often close to the centrosome [16,17,18]. Telomere bouquet formation is driven by the expression of the meiotic prophase-specific proteins TERB1 and TERB2 in most metazoans [19,20,21,22,23], HIM-8/ZIM2/ZIM-1/ZIM-3 in Caenorhabditis elegans [24,25], Ndj in Saccharomyces cerevisiae [26,27], and Bqt and Bqt in Schizosaccharomyces pombe [28]. Once meiotic CMs are complete, the telomere bouquet dissociates from the NE

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