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PubMed2000

Towards a covering set of protein family profiles.

Evolutionary classification leads to an economical description of the protein sequence universe because attributes of function and structure are inherited in protein families. Efficient strategies of functional and structural genomics therefore target one representative from each family. Enumerating all families and establishing family membership consistently based on sequence similarities are nontrivial computational problems. Emerging concepts and caveats of global sequence clustering are reviewed. Explicit multiple alignments coupled with neighbourhood analysis lead to domain segmentation, and hierarchical unification helps to resolve conflicts and validate clusters. Eventually, every part of every sequence will be assigned to a domain family which is uniquely associated with a fold and a molecular function.

Amino Acid Sequence↗
PubMed2000

Lipid-rich diffuse malignant mesothelioma: a case report.

An 80-year old man presented with shortness of breath and was found to have a large right pleural effusion. Cytology of the pleural fluid showed atypical papillary clusters of epithelioid cells. Multiple white-yellow nodules studding the pleural surfaces were seen at thoracoscopy, and biopsies showed solid and papillary clusters of large epithelioid cells with abundant cytoplasm filled with clear vacuoles. Special stains and electron microscopic findings indicated that the tumor was a diffuse malignant mesothelioma with numerous intracytoplasmic lipid vacuoles. Fat stain may be useful at time of frozen section for a pleural-based tumor with vacuolated cells, and the presence of lipid vacuoles in a pleural-based tumor does not exclude diffuse malignant mesothelioma.

Aged↗
PubMed2005

Detecting clusters of different geometrical shapes in microarray gene expression data.

MOTIVATION: Clustering has been used as a popular technique for finding groups of genes that show similar expression patterns under multiple experimental conditions. Many clustering methods have been proposed for clustering gene-expression data, including the hierarchical clustering, k-means clustering and self-organizing map (SOM). However, the conventional methods are limited to identify different shapes of clusters because they use a fixed distance norm when calculating the distance between genes. The fixed distance norm imposes a fixed geometrical shape on the clusters regardless of the actual data distribution. Thus, different distance norms are required for handling the different shapes of clusters. RESULTS: We present the Gustafson-Kessel (GK) clustering method for microarray gene-expression data. To detect clusters of different shapes in a dataset, we use an adaptive distance norm that is calculated by a fuzzy covariance matrix (F) of each cluster in which the eigenstructure of F is used as an indicator of the shape of the cluster. Moreover, the GK method is less prone to falling into local minima than the k-means and SOM because it makes decisions through the use of membership degrees of a gene to clusters. The algorithmic procedure is accomplished by the alternating optimization technique, which iteratively improves a sequence of sets of clusters until no further improvement is possible. To test the performance of the GK method, we applied the GK method and well-known conventional methods to three recently published yeast datasets, and compared the performance of each method using the Saccharomyces Genome Database annotations. The clustering results of the GK method are more significantly relevant to the biological annotations than those of the other methods, demonstrating its effectiveness and potential for clustering gene-expression data. AVAILABILITY: The software was developed using Java language, and can be executed on the platforms that JVM (Java Virtual Machine) is running. It is available from the authors upon request. SUPPLEMENTARY INFORMATION: Supplementary data are available at http://dragon.kaist.ac.kr/gk.

Algorithms↗
PubMed1991

Patterns of connectivity in the cat sensory-motor cortex: a light and electron microscope analysis of the projection arising from area 3a.

Through its complex network of interconnections, each of the functionally specialized subdivisions in the cat primary somatosensory cortex may provide the motor cortex with different input and thus play a unique role in motor behavior. Areas 2 and 3a receive separate peripheral information. Cells in both regions project directly to the cat motor cortex but are thought to target different populations of neurons. In this study the morphology and distribution patterns of the area 3a projection to the motor cortex were compared to previous findings on the projection from area 2. Also, details of the projection from area 3a to area 2 were studied. Injections of Phaseolus vulgaris leucoagglutinin were made into area 3a and fixed brain tissue was processed for immunohistochemical staining of this anterograde tracer. Tissue was examined with the light microscope to determine the patterns of the 3a projections to area 2 and motor cortex, area 4. Axons arising from cells in area 3a terminated in multiple column-like clusters in both motor cortex and area 2. The small number of cells labeled at the injection sites suggested that multiple foci of the 3a fibers are formed by collateral axonal branches of the same neurons. The topography of the projection from area 3a to the motor cortex was more clearly defined than that from area 3a to area 2. Electron microscope analysis determined the laminar distribution and types of synapses formed between area 3a efferents and their target neurons. A high proportion of synapses was found in layer III in both target regions. However, unlike in area 4, labeled terminals were sparse in laminae I and II of area 2. Axospinous synapses were slightly more numerous than axodendritic synapses, but both were distributed similarly throughout the thickness of the cortex. In area 2 the axospinous synapses accounted for 63% of synapses and in area 4 for 57% of synapses. No axosomatic synapses were detected.

Animals↗
PubMed2006

The molecular phylogeny of the genus Rhizopus based on rDNA sequences.

In order to establish the molecular phylogeny of the genus Rhizopus, three molecules of the ribosomal RNA-encoding DNA (rDNA), complete 18S, internal transcribed spacer (ITS)1-5.8S-ITS2, and 28S D1/D2 regions of all the species of the genus were sequenced. Phylogenetic trees showed three major clusters corresponding to the three groups in the current morphological taxonomy, microsporus-group, stolonifer-group, and R. oryzae. R. stolonifer var. lyococcos was clustered independently from the major clusters. R. schipperae clustered differently in all trees. Strains of R. sexualis had multiple ITS sequences. A. rouxii clustered with R. oryzae. These results indicate the possibility of molecular identification of species groups using rDNA sequencing. Reclassification of the genus might be appropriate.

Base Sequence↗
PubMed2005

[Space distribution of low birth weight in Sergipe, Brazil, 1995/1998].

This study analyzes the spatial distribution of low birth weight (LBW) in the State of Sergipe, Brazil, evaluating the event as a health indicator. The analysis was based on 166,312 live births in the 75 municipalities in the State, using an ecological approach. Four methods were used: cluster analysis, correlation analysis, multiple regression analysis, and multiple comparisons (Tukey). The study shows internal homogeneity in the municipalities' health districts and in the groups resulting from the cluster analysis. Considering a 10% loss of information, seven groups were identified, two of which were residues (Aracaju and Porto da Folha). There is a downward trend in LBW in Sergipe (with a mean of 6.97% during the period), reflecting a slight improvement in quality of life. The causes suggest relations with the environment and are influenced by spatial occupation patterns. The percentage of LBW is a useful indicator of individual risk, but as a collective health indicator it does not appear capable of expressing differences between regions that do not display strong inter-variability.

Brazil↗
PubMed2003

Low cost, highly effective parallel computing achieved through a Beowulf cluster.

A Beowulf cluster is a means of bringing together several computers and using software and network components to make this cluster of computers appear and function as one computer with multiple parallel computing processors. A cluster of computers can provide comparable computing power usually found only in very expensive super computers or servers.

Benchmarking↗
PubMed1999

Clustering of radiation-produced breaks along chromosomes: modelling the effects on chromosome aberrations.

PURPOSE: For high-LET radiations, and perhaps even for hard X-rays, DNA double-strand breaks (dsb) are clustered nonrandomly along chromosomes; disproportionately, many inter-dsb segments are less than a few Mbp (10(6) base pairs). The implications of such dsb clustering for chromosome aberrations are analysed. METHODS: Chromosome segments between different dsb within one dsb cluster are assumed too small to detect in the aberration assay. Enumeration or Monte-Carlo computer simulations are used to compute the relative frequencies of many observable aberration patterns: apparently simple or visibly complex. The theoretical predictions are compared with X-ray data for human fibroblasts, involving painted chromosomes 1, 2, 4, 5, 7 or 13. RESULTS AND CONCLUSIONS: Surprisingly, cryptic dsb multiplicity does not affect the frequency ratios predicted for aberration patterns by a random breakage-and-rejoining model. The model is generally consistent with current data on many different types of aberrations, whether or not dsb usually occur in cryptic clusters. For a Revell-type exchange model, however, the predictions do depend on clustering configurations; they gradually approach the predictions of the breakage-and-rejoining model as average cluster multiplicity increases. The model is consistent with the data, for example with the ratio of visibly complex to apparently simple aberrations, only if there is considerable dsb clustering even at low-LET, with approximately 1.5 or more reactive dsb per cluster on average.

Chromosome Aberrations↗
PubMed1998

Enzymatic synthesis of N-linked oligosaccharides terminating in multiple sialyl-Lewis(x) and GalNAc-Lewis(x) determinants: clustered glycosides for studying selectin interactions.

Galactosyltransferase, sialyltransferase, and fucosyltransferase were used to create a panel of complex oligosaccharides that possess multiple terminal sialyl-Le(x) (NeuAc alpha 2-3Gal[Fuc alpha 1-3] beta 1-4GlcNAc) and GalNAc-Le(x) (GalNAc[Fuc alpha 1-3]beta 1-4GlcNAc). The enzymatic synthesis of tyrosinamide biantennary, triantennary, and tetraantennary N-linked oligosaccharides bearing multiple terminal sialyl-Le(x) was accomplished on the 0.5 mumol scale and the purified products were characterized by electrospray MS and 1H NMR. Likewise, biantennary and triantennary tyrosinamide oligosaccharides bearing multiple terminal GalNAc-Le(x) determinants were synthesized and similarly characterized. The transfer kinetics of human milk alpha 3/4-fucosyltransferase were compared for biantennary oligosaccharide acceptor substrates possessing Gal beta 1-4GlcNAc, GalNAc beta 1-4GlcNAc, and NeuAc alpha 2-3Gal beta 1-4GlcNAc which established NeuAc alpha 2-3Gal beta 1-4GlcNAc as the most efficient acceptor substrate. The resulting complex oligosaccharides were chemically tethered through the tyrosinamide aglycone to the surface of liposomes containing phosphatidylthioethanol, resulting in the generation of glycoliposomes probe which will be useful to study relationships between binding affinity and the micro- and macro-clustering of selectin ligand.

Acetylgalactosamine↗
PubMed2004

Recombination within a nucleotide-binding-site/leucine-rich-repeat gene cluster produces new variants conditioning resistance to soybean mosaic virus in soybeans.

The soybean Rsv1 gene for resistance to soybean mosaic virus (SMV; Potyvirus) has previously been described as a single-locus multi-allelic gene mapping to molecular linkage group (MLG) F. Various Rsv1 alleles condition different responses to the seven (G1-G7) described strains of SMV, including extreme resistance, localized and systemic necrosis, and mosaic symptoms. We describe the cloning of a cluster of NBS-LRR resistance gene candidates from MLG F of the virus-resistant soybean line PI96983 and demonstrate that multiple genes within this cluster interact to condition unique responses to SMV strains. In addition to cloning 3gG2, a strong candidate for the major Rsv1 resistance gene from PI96983, we describe various unique resistant and necrotic reactions coincident with the presence or absence of other members of this gene cluster. Responses of recombinant lines from a high-resolution mapping population of PI96983 (resistant) x Lee 68 (susceptible) demonstrate that more than one gene in this region of the PI96983 chromosome conditions resistance and/or necrosis to SMV. In addition, the soybean cultivars Marshall and Ogden, which carry other previously described Rsv1 alleles, are shown to possess the 3gG2 gene in a NBS-LRR gene cluster background distinct from PI96983. These observations suggest that two or more related non-TIR-NBS-LRR gene products are likely involved in the allelic response of several Rsv1-containing lines to SMV.

Base Sequence↗
PubMed2005

Iron-sulfur cluster biosynthesis in photosynthetic organisms.

Iron-sulfur (Fe/S) cluster containing proteins are widely distributed in nature and are involved in numerous processes including electron transfer, metabolic reactions, sensing, signaling, and regulation of gene expression. The knowledge about the biogenesis of Fe/S clusters, and the assembly and maturation of Fe/S cluster containing proteins is still limited, especially in photosynthetic organisms. In most organisms analyzed so far the biogenesis of Fe/S clusters involves more than one machinery. The additional compartment in photoautotrophic organisms, the plastids, presents an additional challenge for the regulation of Fe/S cluster biogenesis. The requirement for Fe/S proteins in multiple chloroplast processes argues that Fe/S cluster assembly is an essential part of plastid functionality. This review focuses on the interesting and unique aspects of Fe/S cluster biogenesis in photosynthetic organisms and compares them to what is known in other organisms.

Animals↗
PubMed2004

Permutation pattern discovery in biosequences.

Functionally related genes often appear in each other's neighborhood on the genome; however, the order of the genes may not be the same. These groups or clusters of genes may have an ancient evolutionary origin or may signify some other critical phenomenon and may also aid in function prediction of genes. Such gene clusters also aid toward solving the problem of local alignment of genes. Similarly, clusters of protein domains, albeit appearing in different orders in the protein sequence, suggest common functionality in spite of being nonhomologous. In the paper, we address the problem of automatically discovering clusters of entities, be they genes or domains: we formalize the abstract problem as a discovery problem called the (pi)pattern problem and give an algorithm that automatically discovers the clusters of patterns in multiple data sequences. We take a model-less approach and introduce a notation for maximal patterns that drastically reduces the number of valid cluster patterns, without any loss of information, We demonstrate the automatic pattern discovery tool on motifs on E. Coli protein sequences.

Algorithms↗
PubMed2005

Quantifying visual similarity in clinical iconic graphics.

OBJECTIVE: The use of icons and other graphical components in user interfaces has become nearly ubiquitous. The interpretation of such icons is based on the assumption that different users perceive the shapes similarly. At the most basic level, different users must agree on which shapes are similar and which are different. If this similarity can be measured, it may be usable as the basis to design better icons. DESIGN: The purpose of this study was to evaluate a novel method for categorizing the visual similarity of graphical primitives, called Presentation Discovery, in the domain of mammography. Six domain experts were given 50 common textual mammography findings and asked to draw how they would represent those findings graphically. Nondomain experts sorted the resulting graphics into groups based on their visual characteristics. The resulting groups were then analyzed using traditional statistics and hypothesis discovery tools. Strength of agreement was evaluated using computational simulations of sorting behavior. MEASUREMENTS: Sorter agreement was measured at both the individual graphical and concept-group levels using a novel simulation-based method. "Consensus clusters" of graphics were derived using a hierarchical clustering algorithm. RESULTS: The multiple sorters were able to reliably group graphics into similar groups that strongly correlated with underlying domain concepts. Visual inspection of the resulting consensus clusters indicated that graphical primitives that could be informative in the design of icons were present. CONCLUSION: The method described provides a rigorous alternative to intuitive design processes frequently employed in the design of icons and other graphical interface components.

Algorithms↗
PubMed2007

Discovery of morphological subgroups that correlate with severity of symptoms in interstitial cystitis: a proposed biopsy classification system.

PURPOSE: We identified morphologically distinct subgroups in interstitial cystitis using cluster analysis and investigated the associations between cluster membership and urinary symptoms. MATERIALS AND METHODS: Of 637 patients enrolled in the Interstitial Cystitis Data Base Study 203 (32%) provided bladder biopsies at baseline screening, representing the focus of this analysis. A cluster analysis algorithm implemented in SAS PROC CLUSTER using standardized distances to measure the dissimilarity of each pair of patients with respect to select histopathological features was used to construct subgroups of these patients. Multivariate regression models for baseline nighttime and 24-hour voiding frequency, urinary urgency and pain were developed, incorporating indicator variables for cluster membership as predictors. Longitudinal urinary symptom profiles during 3 years of followup were also compared among the morphology clusters. RESULTS: Three morphology clusters were identified, corresponding to unique pathological groupings. In cluster C2 7 patients showed multiple pathological features of parenchymal damage, including several inflammatory features. In cluster C1 17 patients was characterized by complete denudation of the urothelium and variable edema. In cluster C0 in 179 patients none of the pathological features were present above the specified thresholds for C2. Cluster membership was significantly associated with baseline nighttime and 24-hour frequency (p <0.001, and with urinary urgency (p = 0.03). These significant increases in baseline symptom severity among clusters from C0 to C1 to C2 persisted throughout the 3 years of followup. CONCLUSIONS: These results suggest an important role for histopathological features in the predictive modeling of interstitial cystitis symptoms.

Adult↗
PubMed2005

Heterologous expression of novobiocin and clorobiocin biosynthetic gene clusters.

A method was developed for the heterologous expression of biosynthetic gene clusters in different Streptomyces strains and for the modification of these clusters by single or multiple gene replacements or gene deletions with unprecedented speed and versatility. Lambda-Red-mediated homologous recombination was used for genetic modification of the gene clusters, and the attachment site and integrase of phage phiC31 were employed for the integration of these clusters into the heterologous hosts. This method was used to express the gene clusters of the aminocoumarin antibiotics novobiocin and clorobiocin in the well-studied strains Streptomyces coelicolor and Streptomyces lividans, which, in contrast to the natural producers, can be easily genetically manipulated. S. coelicolor M512 derivatives produced the respective antibiotic in yields comparable to those of natural producer strains, whereas S. lividans TK24 derivatives were at least five times less productive. This method could also be used to carry out functional investigations. Shortening of the cosmids' inserts showed which genes are essential for antibiotic production.

Amino Acid Sequence↗
PubMed1998

Multiple exon screening using restriction endonuclease fingerprinting (REF): detection of six novel mutations in the L1 cell adhesion molecule (L1CAM) gene.

Restriction endonuclease fingerprinting (REF) has been utilized to screen 19 of the 28 exons in the L1CAM gene using only 5 PCR reactions. The clustered exons were amplified and the PCR products were subjected to endonuclease digestion and subsequent gel electrophoresis to produce a highly informative fingerprint for each PCR product. An alteration in the fingerprint, when compared to a control, determined the specific DNA fragment containing the mutation. Sequencing of the corresponding exon and flanking region was done to determine the precise location of the mutation. Using this method we have identified 6 novel mutations in the L1CAM gene in 5 patients with X-linked hydrocephalus and 2 patients with MASA. One of the mutations was common to both a patient with HSAS and a patient with MASA. The utilization of REF will allow for easier and quicker detection of mutations in the L1CAM gene. This method should be applicable for screening other genes with multiple, clustered exons.

Aphasia↗
PubMed1999

Redox Behavior of [H(6)(-)(n)()Ni(38)Pt(6)(CO)(48)](n)()(-) (n = 4-6) Anions: A Series of Metal Carbonyl Clusters Displaying Electron-Sink Features.

An investigation of the chemical and electrochemical redox behavior of the bimetallic [H(6)(-)(n)()Ni(38)Pt(6) (CO)(48)](n)()(-) (n = 4-6) clusters shows that they display electron-sink features encompassing up to six different oxidation states. As a corollary, these studies provide an indirect proof of the presence of hydride atoms where n = 4 and 5. The difference in the formal electrode potentials of consecutive redox couples of both [HNi(38)Pt(6) (CO)(48)](5)(-) and [Ni(38)Pt(6) (CO)(48)](6)(-) is almost constant and amounts on the average to ca. 0.33 and 0.28 V, respectively. Such constancy of DeltaE within each species points out the absence of a well-defined HOMO-LUMO gap in both clusters. Besides, its value is an indication of their semiconductor rather than metallic nature. A plot of the average DeltaE exhibited by the known carbonyl clusters displaying electrochemically reversible multiple redox changes versus their nuclearity suggests that the transition from semiconductor to metallic behavior might occur upon a ca. 50% increase of the today available cluster nuclearities.

Journal Article↗
PubMed1987

Multiple sclerosis and the workplace: report of an industry-based cluster.

Eleven cases of MS occurred within a 10-year period in a zinc-related manufacturing plant. The observed disease incidence was greater than expected from population data, using multiple approaches to statistical analysis (p less than or equal to 0.01). A case-control study, performed to examine several zinc parameters in blood, failed to indicate specific abnormalities among the MS patients, but all subjects (both MS and controls) working in the plant demonstrated higher serum zinc levels than all subjects (MS and controls) not working there.

Age Factors↗