Bioinformatics Advance Access published online on May 5, 2007
Bioinformatics, doi:10.1093/bioinformatics/btm230
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Phenotypic clustering of yeast mutants based on kinetochore microtubule dynamics
1Department of Cell Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037
2Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115
*To whom correspondence should be addressed. Dr. Khuloud Jaqaman, E-mail: kjaqaman{at}scripps.edu
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Abstract |
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Motivation: Kinetochores are multi-protein 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.
Results: We have developed a hierarchical, agglomerative clustering algorithm that groups S. 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 sub-complexes and pathways for the regulation of MT dynamics.
Availability: The clustering code, written in MATLAB, can be downloaded from http://lccb.scripps.edu. ("download" hyperlink at bottom of website).
Supplementary Information: Supplementary text, three supplementary figures and two supplementary tables are submitted with the manuscript
Associate Editor: Prof. Martin Bishop
These authors contributed equally to this work.
Received on February 17, 2007; revised on April 24, 2007; accepted on April 25, 2007
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