Phenotypic clustering of yeast mutants based on kinetochore microtubule dynamics.
BACKGROUND
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.


RESULTS
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.


BACKGROUND
The clustering code, written in Matlab, can be downloaded from http://lccb.scripps.edu. ('download' hyperlink at bottom of website).


BACKGROUND
Supplementary data are available at Bioinformatics online.
Jaqaman
K
K
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. kjaqaman@scripps.edu
Dorn
J F
JF
Marco
E
E
Sorger
P K
PK
Danuser
G
G
D000465:Algorithms; D016000:Cluster Analysis; D007700:Kinetics; D018386:Kinetochores / Q000502:physiology*; D008870:Microtubules / Q000502:physiology*; D008954:Models, Biological; D009154:Mutation; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000145:classification* / Q000502:physiology* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013696:Temperature
D029701:Saccharomyces cerevisiae Proteins