Data analysis plays an indispensable role for understanding various phenomena. Cluster analysis, primitive exploration with little or no prior knowledge, consists of research developed across a wide variety of communities. The diversity, on one hand, equips us with many tools. On the other hand, the profusion of options causes confusion. We survey clustering algorithms for data sets appearing in statistics, computer science, and machine learning, and illustrate their applications in some benchmark data sets, the traveling salesman problem, and bioinformatics, a new field attracting intensive efforts. Several tightly related topics, proximity measure, and cluster validation, are also discussed.

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Survey of clustering algorithms

The mean trophic level of the species groups reported in Food and Agricultural Organization global fisheries statistics declined from 1950 to 1994. This reflects a gradual transition in landings from long-lived, high trophic level, piscivorous bottom fish toward short-lived, low trophic level invertebrates and planktivorous pelagic fish. This effect, also found to be occurring in inland fisheries, is most pronounced in the Northern Hemisphere. Fishing down food webs (that is, at lower trophic levels) leads at first to increasing catches, then to a phase transition associated with stagnating or declining catches. These results indicate that present exploitation patterns are unsustainable.

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Fishing Down Marine Food Webs

Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor.

Gene regulation by steroid hormones.

The RXR heterodimers and orphan receptors

The Ikaros family in lymphocyte development.

Retinoid X receptor α‐null (RXRα-null) mutants exhibit hypoplasia of their ventricular myocardium and die at the fetal stage. In the present study, we wished to determine whether transgenic re-expression of RXRα in mutant cardiac myocytes could rescue these defects. Two transgenic mouse lines specifically overexpressing an RXRα protein in cardiomyocytes were generated, using the cardiac α-myosin heavy chain (α-MHC) promoter. Breeding the high copy number transgenic line onto an RXRα-null genetic background did not prevent the myocardial hypoplasia and fetal lethality associated with the RXRα‐/‐ genotype, even though the transgene was expressed in the ventricles as early as 10.5 days post-coitum. These data suggest that the RXRα function involved in myocardial growth may correspond to a non‐cell-autonomous requirement for a signal orchestrating the growth and differentiation of myocytes. Interestingly, the adult transgenic mice developed a dilated cardiomyopathy, associated with myofibrillar abnormalities and specific deficiencies in respiratory chain complexes I and II, thus providing an additional model for this genetically complex disease. J. Clin. Invest. 105:387‐394 (2000).

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RXRα overexpression in cardiomyocytes causes dilated cardiomyopathy but fails to rescue myocardial hypoplasia in RXRα-null fetuses

The Ikaros transcription factor is crucial for many aspects of hematopoiesis. Loss of function mutations in IKZF1, the gene encoding Ikaros, have been implicated in adult and pediatric B cell acute lymphoblastic leukemia (B-ALL). These mutations result in haploinsufficiency of the Ikaros gene in approximately half of the cases. The remaining cases contain more severe or compound mutations that lead to the generation of dominant-negative proteins or complete loss of function. All IKZF1 mutations are associated with a poor prognosis. Here we review the current genetic, clinical and mechanistic evidence for the role of Ikaros as a tumor suppressor in B-ALL.

Function of Ikaros as a tumor suppressor in B cell acute lymphoblastic leukemia

The IKZF1 gene encodes the Ikaros transcription factor, a key regulator of lymphocyte differentiation.1 IKZF1 is mutated in 20–30% of B-cell acute lymphoblastic leukemia (B-ALL) mostly by genomic deletions.2, 3, 4 Several reports have shown that IKZF1 deletions are associated with an adverse prognosis, especially in pediatric patients.3, 4, 5, 6, 7, 8, 9, 10 Ikaros mutations fall mainly into three types: (a) deletions of exons 4–7 (Δ4–7), which lead to the synthesis of the Ikaros-6 (Ik6) dominant-negative isoform; (b) deletions of exons 2–7 (Δ2–7), which delete the initiation codon and lead to haploinsufficiency; and (c) larger deletions of various sizes, which affect the coding exons (referred to below as ‘complete’ deletions). Thus, IKZF1 mutations have until now been separated into dominant-negative and haploinsufficient groups. Here we report that about 20% of B-ALL patients with IKZF1 mutations present two distinct deletions. These deletions are biallelic, leading to a complete loss of Ikaros function, or biclonal, marking distinct clones within the leukemia. These results highlight a more complex picture of IKZF1 loss of function in B-ALL than thought previously.

Philippe Kastner

Papers

The Ikaros family in lymphocyte development.

RXRα overexpression in cardiomyocytes causes dilated cardiomyopathy but fails to rescue myocardial hypoplasia in RXRα-null fetuses

Function of Ikaros as a tumor suppressor in B cell acute lymphoblastic leukemia

Biclonal and biallelic deletions occur in 20% of B-ALL cases with IKZF1 mutations.

Retinoic Acid Receptors and Binding Proteins in Human Skin