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A generalized model for multi-marker analysis of cell cycle progression in synchrony experiments.

Mayhew MB, Robinson JW, Jung B, Haase SB, Hartemink AJ - Bioinformatics (2011)

Bottom Line: We use our model to estimate the duration of post-cytokinetic attachment between a S.cerevisiae mother and daughter cell.The Java implementation is fast and extensible, and includes a graphical user interface.Our model provides a powerful and flexible cell cycle analysis tool, suitable to any type or combination of binary markers.

View Article: PubMed Central - PubMed

Affiliation: Program in Computational Biology and Bioinformatics, Department of Computer Science, Center for Systems Biology, Institute for Genome Sciences and Policy, Duke University, Durham, NC 27708, USA. michael.mayhew@duke.edu

ABSTRACT

Motivation: To advance understanding of eukaryotic cell division, it is important to observe the process precisely. To this end, researchers monitor changes in dividing cells as they traverse the cell cycle, with the presence or absence of morphological or genetic markers indicating a cell's position in a particular interval of the cell cycle. A wide variety of marker data is available, including information-rich cellular imaging data. However, few formal statistical methods have been developed to use these valuable data sources in estimating how a population of cells progresses through the cell cycle. Furthermore, existing methods are designed to handle only a single binary marker of cell cycle progression at a time. Consequently, they cannot facilitate comparison of experiments involving different sets of markers.

Results: Here, we develop a new sampling model to accommodate an arbitrary number of different binary markers that characterize the progression of a population of dividing cells along a branching process. We engineer a strain of Saccharomyces cerevisiae with fluorescently labeled markers of cell cycle progression, and apply our new model to two image datasets we collected from the strain, as well as an independent dataset of different markers. We use our model to estimate the duration of post-cytokinetic attachment between a S.cerevisiae mother and daughter cell. The Java implementation is fast and extensible, and includes a graphical user interface. Our model provides a powerful and flexible cell cycle analysis tool, suitable to any type or combination of binary markers.

Availability: The software is available from: http://www.cs.duke.edu/~amink/software/cloccs/.

Contact: michael.mayhew@duke.edu; amink@cs.duke.edu.

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Related in: MedlinePlus

Early in the cell cycle, a budding yeast mother cell undergoes a period of growth (G1). Just prior to the time of transition from G1 to the period of DNA replication (S phase), the myosin ring appears at the site of bud formation (red structure); the bud becomes visible shortly thereafter. Around the same time, the spindle pole body (SPB; green structure) duplicates. Now in S phase, the mother cell replicates its genome (blue bars) within the nucleus (nucleus not shown). Concurrently, the two SPBs start to separate from one another, forming a short mitotic spindle. In G2/M phase, the two SPBs separate further, forming a long mitotic spindle and pulling the nuclei containing replicated chromosomes into the mother and daughter cells, respectively. Following mitosis, the cell undergoes cytokinesis in which the myosin ring constricts to separate the two cytoplasms and then breaks down. Enzymatic processes must synthesize mother and daughter cell walls before the two cells can separate.
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Figure 1: Early in the cell cycle, a budding yeast mother cell undergoes a period of growth (G1). Just prior to the time of transition from G1 to the period of DNA replication (S phase), the myosin ring appears at the site of bud formation (red structure); the bud becomes visible shortly thereafter. Around the same time, the spindle pole body (SPB; green structure) duplicates. Now in S phase, the mother cell replicates its genome (blue bars) within the nucleus (nucleus not shown). Concurrently, the two SPBs start to separate from one another, forming a short mitotic spindle. In G2/M phase, the two SPBs separate further, forming a long mitotic spindle and pulling the nuclei containing replicated chromosomes into the mother and daughter cells, respectively. Following mitosis, the cell undergoes cytokinesis in which the myosin ring constricts to separate the two cytoplasms and then breaks down. Enzymatic processes must synthesize mother and daughter cell walls before the two cells can separate.

Mentions: Cell division is a process fundamental to the growth, development and reproduction of every living organism. In the case of the budding yeast, Saccharomyces cerevisiae, cell division entails a complex and highly regulated series of morphological and genetic changes (Fig. 1). To better understand these changes—and thereby the nature of budding yeast cell cycle progression—researchers track the status of certain cellular features that mark progress through the cell division cycle.Fig. 1.


A generalized model for multi-marker analysis of cell cycle progression in synchrony experiments.

Mayhew MB, Robinson JW, Jung B, Haase SB, Hartemink AJ - Bioinformatics (2011)

Early in the cell cycle, a budding yeast mother cell undergoes a period of growth (G1). Just prior to the time of transition from G1 to the period of DNA replication (S phase), the myosin ring appears at the site of bud formation (red structure); the bud becomes visible shortly thereafter. Around the same time, the spindle pole body (SPB; green structure) duplicates. Now in S phase, the mother cell replicates its genome (blue bars) within the nucleus (nucleus not shown). Concurrently, the two SPBs start to separate from one another, forming a short mitotic spindle. In G2/M phase, the two SPBs separate further, forming a long mitotic spindle and pulling the nuclei containing replicated chromosomes into the mother and daughter cells, respectively. Following mitosis, the cell undergoes cytokinesis in which the myosin ring constricts to separate the two cytoplasms and then breaks down. Enzymatic processes must synthesize mother and daughter cell walls before the two cells can separate.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3117372&req=5

Figure 1: Early in the cell cycle, a budding yeast mother cell undergoes a period of growth (G1). Just prior to the time of transition from G1 to the period of DNA replication (S phase), the myosin ring appears at the site of bud formation (red structure); the bud becomes visible shortly thereafter. Around the same time, the spindle pole body (SPB; green structure) duplicates. Now in S phase, the mother cell replicates its genome (blue bars) within the nucleus (nucleus not shown). Concurrently, the two SPBs start to separate from one another, forming a short mitotic spindle. In G2/M phase, the two SPBs separate further, forming a long mitotic spindle and pulling the nuclei containing replicated chromosomes into the mother and daughter cells, respectively. Following mitosis, the cell undergoes cytokinesis in which the myosin ring constricts to separate the two cytoplasms and then breaks down. Enzymatic processes must synthesize mother and daughter cell walls before the two cells can separate.
Mentions: Cell division is a process fundamental to the growth, development and reproduction of every living organism. In the case of the budding yeast, Saccharomyces cerevisiae, cell division entails a complex and highly regulated series of morphological and genetic changes (Fig. 1). To better understand these changes—and thereby the nature of budding yeast cell cycle progression—researchers track the status of certain cellular features that mark progress through the cell division cycle.Fig. 1.

Bottom Line: We use our model to estimate the duration of post-cytokinetic attachment between a S.cerevisiae mother and daughter cell.The Java implementation is fast and extensible, and includes a graphical user interface.Our model provides a powerful and flexible cell cycle analysis tool, suitable to any type or combination of binary markers.

View Article: PubMed Central - PubMed

Affiliation: Program in Computational Biology and Bioinformatics, Department of Computer Science, Center for Systems Biology, Institute for Genome Sciences and Policy, Duke University, Durham, NC 27708, USA. michael.mayhew@duke.edu

ABSTRACT

Motivation: To advance understanding of eukaryotic cell division, it is important to observe the process precisely. To this end, researchers monitor changes in dividing cells as they traverse the cell cycle, with the presence or absence of morphological or genetic markers indicating a cell's position in a particular interval of the cell cycle. A wide variety of marker data is available, including information-rich cellular imaging data. However, few formal statistical methods have been developed to use these valuable data sources in estimating how a population of cells progresses through the cell cycle. Furthermore, existing methods are designed to handle only a single binary marker of cell cycle progression at a time. Consequently, they cannot facilitate comparison of experiments involving different sets of markers.

Results: Here, we develop a new sampling model to accommodate an arbitrary number of different binary markers that characterize the progression of a population of dividing cells along a branching process. We engineer a strain of Saccharomyces cerevisiae with fluorescently labeled markers of cell cycle progression, and apply our new model to two image datasets we collected from the strain, as well as an independent dataset of different markers. We use our model to estimate the duration of post-cytokinetic attachment between a S.cerevisiae mother and daughter cell. The Java implementation is fast and extensible, and includes a graphical user interface. Our model provides a powerful and flexible cell cycle analysis tool, suitable to any type or combination of binary markers.

Availability: The software is available from: http://www.cs.duke.edu/~amink/software/cloccs/.

Contact: michael.mayhew@duke.edu; amink@cs.duke.edu.

Show MeSH
Related in: MedlinePlus