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PubMed1987

Utility of cluster analysis in classification of mixed neuropsychiatric patients.

This study examines the hypothesis that reliable neuropsychologically-based subgroups can be found in a mixed neuropsychiatric patient sample (N = 600) and that the subtype membership will be associated with external diagnostic and case history variables. A modified Halstead-Reitan Neuropsychological Test Battery was employed. The sample was randomly divided into two groups of 300 each. Results show three reliable cluster analytically-based groups that differ as a function of level, but not pattern of performance. External validation failed to show the cluster groups to be significantly related to any of the neurodiagnostic or case history variables, except that the severely impaired group had a greater preponderance of organic diagnoses and a longer history of hospitalisation. Caution is warranted in using configural analysis of standard neuropsychological test batteries in an effort to identify subtypes in a mixed neuropsychiatric patient population.

Journal Article↗
PubMed2001

Ribosomal protein gene cluster analysis in eubacterium genomics: homology between Sinorhizobium meliloti strain 1021 and Bacillus subtilis.

The first whole genome sequence of a symbiotic soil bacterium, Sinorhizobium meliloti (formely named Rhizobium meliloti) strain 1021, is due in 2001. As an active participant in the European and North American consortium that has completed this work, our group has sequenced a region on the chromosome containing clusters rpoBC, str, S10, spc and alpha corresponding to 30 protein genes. The structural organization and function of these genes were compared with those of orthologs in another 15 complete eubacterial genomes available in databases. This study, involving the DNA and amino acid sequences as well as the organization of the whole region (gene order, cluster order, etc.), has shown that the phylogenetic tree resulting from a comparison of the amino acid sequence is rather similar to that derived from 16S rRNA sequence data. However, the tree achieved by aligning DNA sequences groups the organisms with a high GC content (>60% GC), while that based on a comparison of gene cluster orientation and organization reveals a greater level of correspondence between the alpha-proteobacteria S.meliloti and the firmicute Bacillus subtilis.

Bacillus subtilis↗
PubMed1986

Cluster analysis: a simple, versatile, and robust algorithm for endocrine pulse detection.

Endocrine signaling provides one critical means of physiological communication within an organism. Many endocrine signals exhibit an episodic or pulsatile configuration. In an effort to provide a versatile and statistically based algorithm for investigating the regulation of endocrine pulse signals, we have formulated a computerized algorithm in which a pulse is defined as a statistically significant increase in a "cluster" of hormone values followed by a statistically significant decrease in a second cluster of values. The increase or decrease is judged in relation to the actual experimental error expressed by the replicates in the presumptive nadir and peak data clusters. The program permits the operator to specify the cluster sizes of test peaks and pre- and postpeak nadirs. This method is largely insensitive to unstable base-line hormone concentrations and is not adversely affected by varying pulse amplitudes, widths, or configurations within the endocrine series. In addition, the simple statistical basis for this algorithm renders it minimally dependent on explicit or a priori assumptions about rates of hormone secretion or disappearance. The program has been validated for false-positive errors against a wide range of intraseries coefficients of variation (4-52%). We have illustrated its performance for profiles of luteinizing hormone, follicle-stimulating hormone, growth hormone, prolactin, adrenocorticotropic hormone, and cortisol and compared these episodic patterns with those of stable serum constituents (total serum protein and calcium), which do not exhibit pulsatile fluctuation.

Adrenocorticotropic Hormone↗
PubMed1998

Infrared microscopic functional group mapping and spectral clustering analysis of hypercholesterolemic rabbit liver.

Fourier transform infrared microscopy has been applied to the characterization of hypercholesterolemic rabbit liver. A combination of the traditional "group frequency" approach to spectral interpretation and the technique of functional group mapping was applied to aid understanding of the spectral changes observed between normal and hypercholesterolemic liver. Using this approach, spectral differences could be attributed to the accumulation of cholesterol esters (most likely in the form of lipoprotein complexes) in the hypercholesterolemic liver. A novel approach, spectral clustering, was used to identify regions of hypercholesterolemic liver tissue which possessed similar spectral (and by inference similar biochemical/histological) properties. Using this approach, a complex data set consisting of 400 discrete spectra acquired from an area of tissue approximately 1 x 1 mm could be reduced to five types of spectra, and the distribution of each type of spectrum within the tissue analyzed.

Algorithms↗
PubMed2004

Biosynthetic pathway and gene cluster analysis of curacin A, an antitubulin natural product from the tropical marine cyanobacterium Lyngbya majuscula.

Curacin A (1) is a potent cancer cell toxin obtained from strains of the tropical marine cyanobacterium Lyngbya majuscula found in Curaçao. Its structure is unique in that it contains the sequential positioning of a thiazoline and cyclopropyl ring, and it exerts its potent cell toxicity through interaction with the colchicine drug binding site on microtubules. A series of stable isotope-labeled precursors were fed to cultures of curacin A-producing strains and, following NMR analysis, allowed determination of the metabolic origin of all atoms in the natural product (one cysteine, 10 acetate units, two S-adenosyl methionine-derived methyl groups) as well as several unique mechanistic insights. Moreover, these incorporation experiments facilitated an effective gene cloning strategy that allowed identification and sequencing of the approximately 64 kb putative curacin A gene cluster. The metabolic system is comprised of a nonribosomal peptide synthetase (NRPS) and multiple polyketide synthases (PKSs) and shows a very high level of collinearity between genes in the cluster and the predicted biochemical steps required for curacin biosynthesis. Unique features of the cluster include (1) all but one of the PKSs are monomodular multifunctional proteins, (2) a unique gene cassette that contains an HMG-CoA synthase likely responsible for formation of the cyclopropyl ring, and (3) a terminating motif that is predicted to function in both product release and terminal dehydrative decarboxylation.

Amino Acid Sequence↗
PubMed1989

Histochemical classification of neck and limb muscle fibers in a turtle, Pseudemys scripta: a study using microphotometry and cluster analysis techniques.

We have attempted to develop an objective, semiquantitative classification of fiber types in turtle neck and limb muscle using microphotometry and multivariate statistical techniques. We first stained serial sections for myosin adenosine triphosphatase (ATPase) (with acid and alkaline preincubation and without preincubation), NADH-diaphorase, and two glycolysis-associated markers, alpha-glycerophosphate dehydrogenase (alpha-GPDH) and glycogen phosphorylase A (GPA). This allowed us to characterize individual muscle fibers in terms of their contraction speed and metabolic properties. Next we used microphotometry to measure the optical density of the reaction product in each fiber, and we subjected the resulting optical density matrix to cluster and discriminant function analyses in order to assign fibers to groups (fiber types) and to determine which stains contribute most to the distinction between groups. As a control, we processed a well characterized mammalian muscle (rat sternomastoid) simultaneously. Our results suggest that both neck and limb muscle in Pseudemys can best be described as falling into three groups: 1) slow oxidative (SO) fibers; 2) fast oxidative glycolytic (FOG) fibers, with relatively high oxidative and glycolytic capacities; and 3) fast glycolytic (Fg) fibers, with low oxidative, low/intermediate alpha-GPDH, and high GPA activities. These three fiber types differ from like-named types in rat muscle both in the pH lability of their myosins and in their metabolic profiles.

Animals↗
PubMed2004

Clustering analysis of the ground-state structure of the vertex-cover problem.

Vertex cover is one of the classical NP-complete problems in theoretical computer science. A vertex cover of a graph is a subset of vertices such that for each edge at least one of the two endpoints is contained in the subset. When studied on Erdo s-Re nyi random graphs (with connectivity c) one observes a threshold behavior: In the thermodynamic limit the size of the minimal vertex cover is independent of the specific graph. Recent analytical studies show that on the phase boundary, for small connectivities c<e , the system is replica symmetric, while for larger connectivities replica symmetry breaking occurs. This change coincides with a change of the typical running time of algorithms from polynomial to exponential. To understand the reasons for this behavior and to compare with the analytical results, we numerically analyze the structure of the solution landscape. For this purpose, we have also developed an algorithm, which allows the calculation of the backbone, without the need to enumerate all solutions. We study exact solutions found with a branch-and-bound algorithm as well as configurations obtained via a Monte Carlo simulation. We analyze the cluster structure of the solution landscape by direct clustering of the states, by analyzing the eigenvalue spectrum of correlation matrices and by using a hierarchical clustering method. All results are compatible with a change at c=e . For small connectivities, the solutions are collected in a finite small number of clusters, while the number of clusters diverges slowly with system size for larger connectivities and replica symmetry breaking, but not one-step replica symmetry breaking (1-RSB) occurs.

Journal Article↗
PubMed2003

Cluster analysis of human autoantibody reactivities in health and in type 1 diabetes mellitus: a bio-informatic approach to immune complexity.

Informatic methodologies are being applied successfully to analyze the complexity of the genome. But beyond the genome, the immune system reflects the state of the body in health and disease. Traditionally, immunologists have reduced the immune system, where possible, to one-to-one relationships between particular antigens and particular antibodies or T-cell clones. Autoimmune diseases, caused by an immune attack against a body component, are usually investigated by following the response to single self-antigens. In this study, we apply informatics to analyze patterns of autoantibodies rather than single species of autoantibodies. This study was designed not to replace traditional approaches to immune diagnosis, but to test whether meaningful patterns of autoantibodies might exist. Using an unbiased solid-phase ELISA antibody test, we detected serum IgG and IgM antibodies in the sera of 20 healthy persons and 20 persons with type 1 diabetes mellitus binding to an array of 87 different antigens, mostly self-antigens. The healthy subjects manifested autoantibodies to a variety of self-antigens, many known to be associated with autoimmune diseases. We investigated the patterns of these autoantibodies using a coupled two-way clustering algorithm developed for analyzing data from gene arrays. We now report that the reactivity patterns of autoantibodies to particular subsets of self-antigens exhibited non-trivial structure, which significantly discriminated between healthy persons and persons with type 1 diabetes. The results show that despite the wide prevalence of autoantibodies, the patterns of reactivity to defined subsets of self-antigens can provide information about the state of the body.

Autoantibodies↗
PubMed2001

Assembly and annotation of human chromosome 2q33 sequence containing the CD28, CTLA4, and ICOS gene cluster: analysis by computational, comparative, and microarray approaches.

Human chromosome 2q33 is an immunologically important region based on the linkage of numerous autoimmune diseases to the CTLA4 locus. Here, we sequenced and assembled 2q33 bacterial artificial chromosome (BAC) clones, resulting in 381,403 bp of contiguous sequence containing genes encoding a NADH: ubiquinone oxidoreductase, the costimulatory receptors CD28, CTLA4, and ICOS, and a HERV-H type endogenous retrovirus located 366 bp downstream of ICOS in the reverse orientation. Genomic microarray expression analysis using differentially activated T-cell RNA against a subcloned CTLA4/ICOS BAC library revealed upregulation of CTLA4 and ICOS sequences, plus antisense ICOS transcripts generated by the HERV-H, suggesting a potential mechanism for ICOS regulation. We identified four nonlinked, polymorphic, simple repetitive sequence elements in this region, which may be used to delineate genetic effects of ICOS and CTLA4 in disease populations. Comparative genomic analysis of mouse genomic Icos sequences revealed 60% sequence identity in the 5' UTR and regions between exon 2 and the 3' UTR, suggesting the importance of ICOS gene function.

Abatacept↗
PubMedDate not supplied

Elemental classification in multi-detector stem images using image analysis clustering techniques.

The multi-detector STEM images form a multi-dimensional measurement space where picture elements of morphologically distinct regions cluster and can be separated for classification using image processing clustering techniques. These images are highly correlated and improve the classification only at the high cost of adding dimensionality. Data reduction techniques which take the class separation into account can be used to compress the useful information carried by these images into a few components to which clustering techniques can be successfully applied. At high magnification, a slight displacement is sometimes observed, which can slightly impair the classification result. The redundancy of the information in the quadrant images suggests their use for phase retrieval - which, added to an energy loss data channel, may greatly improve the classification.

Animals↗