Biomedical subjects

Philippe Kastner

Publications and source records attributed to Philippe Kastner.

3 recordsLinked to original sources

PubMed2003

Fuzzy C-means method for clustering microarray data.

MOTIVATION: Clustering analysis of data from DNA microarray hybridization studies is essential for identifying biologically relevant groups of genes. Partitional clustering methods such as K-means or self-organizing maps assign each gene to a single cluster. However, these methods do not provide information about the influence of a given gene for the overall shape of clusters. Here we apply a fuzzy partitioning method, Fuzzy C-means (FCM), to attribute cluster membership values to genes. RESULTS: A major problem in applying the FCM method for clustering microarray data is the choice of the fuzziness parameter m. We show that the commonly used value m = 2 is not appropriate for some data sets, and that optimal values for m vary widely from one data set to another. We propose an empirical method, based on the distribution of distances between genes in a given data set, to determine an adequate value for m. By setting threshold levels for the membership values, genes which are tigthly associated to a given cluster can be selected. Using a yeast cell cycle data set as an example, we show that this selection increases the overall biological significance of the genes within the cluster. AVAILABILITY: Supplementary text and Matlab functions are available at http://www-igbmc.u-strasbg.fr/fcm/

Algorithms↗

PubMed2002

Ikaros regulates neutrophil differentiation.

The Ikaros gene encodes a zinc finger transcription factor that is selectively expressed by all hematopoietic cells. Although Ikaros is required for lymphocyte differentiation, its role in the myeloid lineage is unclear. We show here that Ikaros expression is temporally regulated during neutrophil differentiation: Ikaros is primarily expressed at immature stages and significantly less so in mature neutrophils. Furthermore Ik(L/L) mice, harboring a hypomorphic mutation at the Ikaros locus, exhibit several defects during neutrophil differentiation. (1) Ik(L/L) fetal livers contain high numbers of neutrophil lineage cells, and this increase is reflected in the number of GM-CSF-dependent progenitor cells. (2) The migratory potential and survival of neutrophil progenitors is altered in vitro. (3) Expression of the Gr-1 marker is delayed and repressed. In contrast, neutrophil function appears normal. These data demonstrate that Ikaros regulates early neutrophil differentiation but is dispensable in mature neutrophils.

Animals↗

PubMed2002

Ikaros is critical for B cell differentiation and function.

The Ikaros gene encodes a zinc-finger transcription factor required during early B cell development, as B-lineage cells are absent in mice lacking Ikaros. Here we describe a novel Ikaros-targeted mouse line carrying a beta-galactosidase reporter in which low amounts of Ikaros proteins remain expressed. In homozygote animals, B cells are absent during fetal development, but develop postnatally from a reduced pool of precursors. In vitro, the proliferation and differentiation of B-lineage progenitors are severely impaired. These defects are attenuated in vivo, but bone marrow B cells display an unusual pattern of cell surface marker expression and show decreased transcript levels for TdT, Rag-1, Rag-2 and lambda 5. These abnormalities suggest a partial block at the proB cell stage of differentiation. In the periphery, mature B cells exhibit a lower activation threshold but form fewer germinal centers in response to antigenic stimulation. Our results show that Ikaros controls multiple aspects of B cell differentiation and function.

Animals↗