Phenotypic clustering of yeast mutants based on kinetochore microtubule dynamics

Harvard University, Cambridge, Massachusetts, United States
Bioinformatics (Impact Factor: 4.98). 08/2007; 23(13):1666-73. DOI: 10.1093/bioinformatics/btm230
Source: PubMed


Kinetochores are multiprotein complexes which mediate chromosome attachment to microtubules (MTs) of the mitotic spindle. They regulate MT dynamics during chromosome segregation. Our goal is to identify groups of kinetochore proteins with similar effects on MT dynamics, revealing pathways through which kinetochore proteins transform chemical and mechanical input signals into cues of MT regulation.
We have developed a hierarchical, agglomerative clustering algorithm that groups Saccharomyces cerevisiae strains based on MT-mediated chromosome dynamics measured by high-resolution live cell microscopy. Clustering is based on parameters of autoregressive moving average (ARMA) models of the probed dynamics. We have found that the regulation of wildtype MT dynamics varies with cell cycle and temperature, but not with the chromosome an MT is attached to. By clustering the dynamics of mutants, we discovered that the three genes IPL1, DAM1 and KIP3 co-regulate MT dynamics. Our study establishes the clustering of chromosome and MT dynamics by ARMA descriptors as a sensitive framework for the systematic identification of kinetochore protein subcomplexes and pathways for the regulation of MT dynamics.
The clustering code, written in Matlab, can be downloaded from ('download' hyperlink at bottom of website).
Supplementary data are available at Bioinformatics online.

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    • "Computationally, the microtubule growing, shortening and other dynamic patterns can be tracked in time-lapse microscopy images, via mixture analysis of hidden Markov models (Altinok et al., 2006; Altınok et al., 2007), minimum shared decomposition of directed graphs derived from the microtubule spots (Swidan et al., 2007), particle filtering (Smal et al., 2008), multiscale tip and body model (Jiang et al., 2005), detecting individual segments and linking (Danuser et al., 2000; Hadjidemetriou et al., 2004; Meijering et al., 2006). Hierarchical, agglomerative clustering analysis of various yeast mutants based on kinetochore microtubule dynamics was also reported (Jaqaman et al., 2007). For developmental biology, visualizing how genes are expressed in living organisms allows us to gain insight in the interactions of gene products. "
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