Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “multiple clustering”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,621 records · Page 90Linked to original sources
PubMed2003

Comprehensive aligned sequence construction for automated design of effective probes (CASCADE-P) using 16S rDNA.

MOTIVATION: Prokaryotic organisms have been identified utilizing the sequence variation of the 16S rRNA gene. Variations steer the design of DNA probes for the detection of taxonomic groups or specific organisms. The long-term goal of our project is to create probe arrays capable of identifying 16S rDNA sequences in unknown samples. This necessitated the authentication, categorization and alignment of the >75 000 publicly available '16S' sequences. Preferably, the entire process should be computationally administrated so the aligned collection could periodically absorb 16S rDNA sequences from the public records. A complete multiple sequence alignment would provide a foundation for computational probe selection and facilitates microbial taxonomy and phylogeny. RESULTS: Here we report the alignment and similarity clustering of 62 662 16S rDNA sequences and an approach for designing effective probes for each cluster. A novel alignment compression algorithm, NAST (Nearest Alignment Space Termination), was designed to produce the uniform multiple sequence alignment referred to as the prokMSA. From the prokMSA, 9020 Operational Taxonomic Units (OTUs) were found based on transitive sequence similarities. An automated approach to probe design was straightforward using the prokMSA clustered into OTUs. As a test case, multiple probes were computationally picked for each of the 27 OTUs that were identified within the Staphylococcus Group. The probes were incorporated into a customized microarray and were able to correctly categorize Staphylococcus aureus and Bacillus anthracis into their correct OTUs. Although a successful probe picking strategy is outlined, the main focus of creating the prokMSA was to provide a comprehensive, categorized, updateable 16S rDNA collection useful as a foundation for any probe selection algorithm.

Algorithms↗
PubMed2001

Childhood leukaemia clustering--fact or artefact?

There is a general belief that the clustering of childhood leukaemia is a widespread phenomenon and that it provides evidence for appreciable environmental influence on the incidence of the disease. We discuss this issue critically, identifying different kinds of clustering and their possible aetiological mechanisms and examining some analyses of British data. We argue that, in some cases, analyses have been used which lead to dubious conclusions, and that, allowing for multiple testing and anecdotal reporting, the total evidence for clustering is at best weak.

Bias↗
PubMed2002

The human homologue of the mouse Surf5 gene encodes multiple alternatively spliced transcripts.

Hu-Surf5 is included within the Surfeit locus, a cluster of six genes originally identified in mouse. In the present study, we have cloned and characterized the Hu-Surf5 gene and its mRNA multiple transcripts. Comparison of the most abundant cDNA and genomic sequence shows that the Hu-Surf5 is spread over a region of approximately 7.5 kb and consists of five exons separated by four introns. The nucleotide sequence of the genomic region flanking the 3'-end of the Hu-Surf5 gene revealed the presence of a processed pseudogene of human ribosomal protein L21 followed by Hu-Surf6 gene. Only 110 bp separate the transcription start site of Hu-Surf5 and Hu-Surf3/L7a gene and the transcription direction is divergent. Earlier studies defined the 110 bp region essential for promoter activity of Hu-Surf3/L7a. Here, we show that this region stimulates transcription with a slightly different efficiency in both directions. The bidirectional promoter lacks an identifiable TATA box and is characterized by a CpG island that extends through the first exon into the first intron of both genes. These features are characteristic of housekeeping genes and are consistent with the wide tissue distribution observed for Hu-Surf5 expression. Hu-Surf5 encodes three different transcripts, Surf-5a, Surf-5b, and Surf-5c, which result from alternative splicing. Two protein products, SURF-5A and SURF-5B have been characterized. Production of chimaeras between the full-length SURF-5A or SURF-5B and the green fluorescent protein (GFP) allowed to localize both proteins in the cytoplasm.

Alternative Splicing↗
PubMed1987

Influence of the catBCE sequence on the phenotypic reversion of a pcaE mutation in Acinetobacter calcoaceticus.

Isofunctional beta-ketoadipate:succinyl coenzyme A transferases I and II are encoded by the pcaE and catE genes, respectively, of Acinetobacter calcoaceticus. The genes are under separate transcriptional control and genetically unlinked. Mutations in the pcaE gene result in a p-hydroxybenzoate-negative (POB-) phenotype, whereas catE mutations cause a benzoate-negative (Ben-) phenotype. A. calcoaceticus ADP125 carries the pcaE3125 mutation and gave rise to POB+ revertants with a frequency of 10(-4). A 5.0-kilobase-pair (kb) EcoRI restriction fragment containing the catBCDE genes possesses two SalI restriction sites separated by 1.5 kb. Removal of the DNA between the SalI sites created a deletion removing the terminal 35 base pairs of the catB gene, the 300-base-pair catC gene, and about 1.1 kb of the 1.2-kb catE gene. Transformation of strain ADP125 with the modified EcoRI fragment lacking the SalI segment produced natural transformants containing this designed deletion with a frequency of 20%. The frequency of POB+ phenotypic reversion of the pcaE3125 mutation in these transformants was more than 300-fold lower than the frequency of phenotypic reversion observed in genetic backgrounds containing the catBCE segment. Alleles created by pcaE phenotypic reversion in a wild-type cat genetic background were unlinked to the cat gene cluster, and revertant transferases were expressed inducibly with the pca genes. Alterations in the restriction pattern of the pca gene cluster in several revertants were observed, indicating that multiple sequence changes have occurred in the pca genes during reversion. Growth of the phenotypic revertants under nonselective conditions resulted in loss of either the POB+ phenotype or both the POB+ and Ben+ phenotypes at high frequency. Southern hybridizations revealed that loss of the POB+ of Ben+ phenotype was due to deletion of the entire pca or cat gene cluster, a loss of at least 16 kb in some strains. Revertants isolated in a catBCE deletion background were stable. These results suggest that enhanced phenotypic reversion of pcaE3125 in wild-type cat background is due to repair of the mutation by recombination between the catBCE and pcaE3125 sequences. Genetic instability of the phenotypic revertants may be attributed to deletion of pca and cat sequences by recombination between regions of homology created as a consequence of pcaE repair.

Acinetobacter↗
PubMed2003

Kernel hierarchical gene clustering from microarray expression data.

MOTIVATION: Unsupervised analysis of microarray gene expression data attempts to find biologically significant patterns within a given collection of expression measurements. For example, hierarchical clustering can be applied to expression profiles of genes across multiple experiments, identifying groups of genes that share similar expression profiles. Previous work using the support vector machine supervised learning algorithm with microarray data suggests that higher-order features, such as pairwise and tertiary correlations across multiple experiments, may provide significant benefit in learning to recognize classes of co-expressed genes. RESULTS: We describe a generalization of the hierarchical clustering algorithm that efficiently incorporates these higher-order features by using a kernel function to map the data into a high-dimensional feature space. We then evaluate the utility of the kernel hierarchical clustering algorithm using both internal and external validation. The experiments demonstrate that the kernel representation itself is insufficient to provide improved clustering performance. We conclude that mapping gene expression data into a high-dimensional feature space is only a good idea when combined with a learning algorithm, such as the support vector machine that does not suffer from the curse of dimensionality. AVAILABILITY: Supplementary data at www.cs.columbia.edu/compbio/hiclust. Software source code available by request.

Algorithms↗
PubMed1975

HL-A antigens in a Chinese population.

The HL-A antigens of a Chinese population now living on the island of Taiwan have been investigated with reagents obtained from and characterized in Caucasian populations and with antisera obtained from Chinese multiparous women. Both HL-A2, the most frequent specificity found, and HL-A9 appear highly heterogeneous in this Chinese population since groups of antisera used to define HL-A2 or 9 in Caucasians gave discordant reactions. Moreover, new associations were found using chi-square and cluster analyses, further demonstrating the complexity of HL-A in this Taiwanese population. Fourteen % of 1183 Chinese multipara sera and 237 sera from multiple tranfused individuals were lymphocytotoxic and could be placed by cluster analysis into three major groups.

Cytotoxicity Tests, Immunologic↗
PubMed2006

Unsupervised classification of single particles by cluster tracking in multi-dimensional space.

In cryo-electron microscopy (cryo-EM) single-particle reconstruction, the heterogeneity of two-dimensional projection image data resulting from the co-existence of different conformational or ligand binding states of a macromolecular complex remains a major obstacle as it impairs the validity of reconstructed density maps and limits the progress toward higher resolution. Classification of cryo-EM data according to the different conformations is difficult because of the coexistence of multiple orientations in a single dataset. Here, we present an unsupervised classification method, termed cluster tracking, which utilizes the continuity in multi-dimensional space induced by angular adjacency of projections in large datasets. In a proof of concept, the testing of cluster tracking on simulated projection data, which were generated from multiple conformations and orientations of an existing volume, produced clusters that are consistent with the conformational identity of the data. The application of the method to experimental cryo-EM projection data is found to result in a partition similar to the one generated by supervised classification.

Algorithms↗
PubMed2000

Multiple scattering in low-energy electron holography

The theory of the low-energy electron point source (LEEPS) microscope is reformulated in matrix form to readily account for multiple scattering. An algorithm is developed for the storage of the structure matrix and an iterative method is used to solve the matrix equation for the structure factor. Examples of small and large clusters of atoms are given to compare single and multiple scattering. A Kirchhoff-Helmholtz transform is used for the reconstruction. We find that in some cases the multiple scattering is too strong and reconstruction is not possible. We give examples which show that, even when multiple scattering is important, one can still obtain reconstructions that reveal the atomic structure both along and lateral to the optical axis. We also compare our results with those found in LEED.

Journal Article↗
PubMed2006

Modifications of brain tissue volumes in facioscapulohumeral dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD), a pathology primarily characterized by involvement of the muscles in the face, shoulder and upper arm, can be associated to several CNS disorders, including sensorineural hearing deficits, schizophrenia, epilepsy and mental retardation. Aim of our study was to verify if brain tissue volumes, as measured by segmentation of MRI studies, are altered in FSHD. Volumes of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) were compared, taking into account head size age and sex, both globally (by multiple regression analysis) and regionally (by optimized voxel-based morphometry-VBM) in thirty patients with FSHD and 39 normal subjects (NS). FSHD patients had significantly lower GM volumes and higher CSF volumes (P < 10(-4)). GM loss showed a borderline correlation with clinical severity (P < 0.05). Brain tissue volumes did not correlate with disease duration, size of the genetic deletion, age at onset and the presence at MRI of WM hyperintensities (detected in 4/22 patients). At VBM three clusters of GM loss were detected, in the left precentral cortex (Brodmann areas 6, 2 and 44, P < 10(-14) corrected for multiple comparisons at cluster level), in the anterior cingulate (Brodmann areas 33, 24 and 11, P < 10(-4)) and in the right fronto-polar region (Brodmann area 10, P < 5.10(-3)). To the best of our knowledge, this is the first study to demonstrate a reduction in GM volume in FSHD. We hypothesize that localized GM loss in FSHD is the consequence of a selective involvement of specific CNS structures.

Adult↗
PubMed2006

MulPSSM: a database of multiple position-specific scoring matrices of protein domain families.

Representation of multiple sequence alignments of protein families in terms of position-specific scoring matrices (PSSMs) is commonly used in the detection of remote homologues. A PSSM is generated with respect to one of the sequences involved in the multiple sequence alignment as a reference. We have shown recently that the use of multiple PSSMs corresponding to an alignment, with several sequences in the family used as reference, improves the sensitivity of the remote homology detection dramatically. MulPSSM contains PSSMs for a large number of sequence and structural families of protein domains with multiple PSSMs for every family. The approach involves use of a clustering algorithm to identify most distinct sequences corresponding to a family. With each one of the distinct sequences as reference, multiple PSSMs have been generated. The current release of MulPSSM contains approximately 33,000 and approximately 38,000 PSSMs corresponding to 7868 sequence and 2625 structural families. A RPS_BLAST interface allows sequence search against PSSMs of sequence or structural families or both. An analysis interface allows display and convenient navigation of alignments and domain hits. MulPSSM can be accessed at http://crick.mbu.iisc.ernet.in/~mulpssm.

Databases, Protein↗
PubMed2004

[Multiple nonlinear statistical method of population genetic structure based on the allelic polymorphism data].

The distribution and structure of the allelic polymorphism data are analyzed and it is pointed out that the distribution of allelic polymorphism data reveals the characteristic of closed data (also named as compositional data or data of constant sum). It is interpreted that the correlation structure of the allelic polymorphism data contains null correlations introduced by "closure" and the statistical distribution of the data is not normal because of its constant row sum, which resulted in great difficulties in analyzing the data with traditional multiple linear statistical methods such as principal component analysis, factor analysis, cluster analysis and canonical correlation analysis. Based on the theory of compositional data analysis proposed by Aitchison in 1982, a multiple nonlinear statistical method originating from the "logratios" approach to the statistical analysis of compositional data is put forward in this paper. As an example, the "logratios" method was used to analyze the genetic structure of TH01 polymorphic loci in Chinese population and the results were compared with those of multiple linear methods such as component principal. It is concluded that the "logratios" multiple nonlinear principle component analysis is a better method with the virtue of sensitivity and specificity for analyzing the genetic structure of population from the data of allelic polymorphism.

Alleles↗
PubMed2006

Mitochondrial disease activates transcripts of the unfolded protein response and cell cycle and inhibits vesicular secretion and oligodendrocyte-specific transcripts.

Mutations in gene products expressed in the mitochondrion cause a nuclear transcriptional response that leads to neurological disease. To examine the extent to which the transcriptional profile was shared among 5 mitochondrial diseases (LHON, FRDA, MELAS, KSS, and NARP), we microarrayed mutant and control groups in N-tera2, SH-SY5Y, lymphoblasts, fibroblasts, myoblasts, muscle, and osteosarcoma cybrids. Many more transcripts were observed to be significantly altered and shared among these 5 mitochondrial diseases and cell types than expected on the basis of random chance, and these genes are significantly clustered with respect to biochemical pathways. Mitochondrial disease activated multiple transcripts of the unfolded protein response (UPR), and of the cell cycle pathway, and low doses of the mitochondrial inhibitor rotenone induced UPR transcripts in the absence of cell death. By contrast, functional clusters inhibited by mitochondrial disease included: vesicular secretion, protein synthesis, and oligodendrogenesis. As it is known that UPR activation specifically inhibits vesicular secretion and protein synthesis, these data support the view that mitochondrial disease and dysfunction triggers the UPR, which in turn causes secretory defects which inhibit cellular migratory, synaptic, and oligodendrocytic functions, providing a testable hypothesis for how mitochondrial dysfunction causes disease. Since ischemic hypoxia, chemical hypoxia, and mitochondrial genetic disease (which could be considered 'genetic hypoxia') produce an overlapping induction of UPR and cell cycle genes which appears to have negative consequences, the modulation of these responses might be of benefit to patients with mitochondrial disease.

Cell Cycle Proteins↗
PubMed2004

Increased rates of spontaneous sister chromatid exchange in lymphocytes of BRCA2+/- carriers of familial breast cancer clusters.

Heterozygous carriers of germ-line mutations of the BRCA2 breast cancer susceptibility gene are predisposed to breast, ovarian, pancreatic and other cancers. The BRCA2 protein is implicated in the maintenance of chromosome stability through its essential function in double-strand DNA repair and recombination. Our previous studies had revealed multiple intrachromosomal rearrangements, duplications, inversions and deletions on 9p23-24 in lymphocytes and fibroblasts of BRCA2+/- members from independently ascertained familial breast cancer clusters. In pursuit of evaluating if there is a subtle genomic instability in BRCA2+/- individuals, we have determined frequencies of spontaneous sister chromatid exchanges (SCEs) in BRCA2 wild-types and BRCA2 mutation carriers of two familial breast cancer clusters. Here, we demonstrate an average increase of 65% of spontaneous SCEs in BRCA2+/- versus BRCA2+/+ family members. In one cluster, the number of metaphases with multiple SCEs was 5-times higher in BRCA2+/- compared to wild-type members, while in the second cluster BRCA2+/- members had 8.9% of metaphases with multiple SCEs compared to a level below detection in BRCA2 wild types. To investigate the correlation between SCE and genomic instability in 9p, we performed fluorescence detection of SCEs and FISH analysis with 9p probes. The frequency of SCE in 9p of BRCA2 mutation carriers was 3-4 fold (P = 0.005) higher compared to BRCA2 wild-types. Collectively, the increased rates of SCE in BRCA2 heterozygous mutation carriers indicate a BRCA2 haploinsufficiency, which might be an important factor for the accumulation of structural chromosomal alterations with the consequence of damage in as yet unidentified genes.

Breast Neoplasms↗
PubMed1998

Identification of a structural determinant for resistance to beta-lactam antibiotics in Gram-positive bacteria.

Streptococcus pneumoniae is the main causal agent of pathologies that are increasingly resistant to antibiotic treatment. Clinical resistance of S. pneumoniae to beta-lactam antibiotics is linked to multiple mutations of high molecular mass penicillin-binding proteins (H-PBPs), essential enzymes involved in the final steps of bacterial cell wall synthesis. H-PBPs from resistant bacteria have a reduced affinity for beta-lactam and a decreased hydrolytic activity on substrate analogues. In S. pneumoniae, the gene coding for one of these H-PBPs, PBP2x, is located in the cell division cluster (DCW). We present here structural evidence linking multiple beta-lactam resistance to amino acid substitutions in PBP2x within a buried cavity near the catalytic site that contains a structural water molecule. Site-directed mutation of amino acids in contact with this water molecule in the "sensitive" form of PBP2x produces mutants similar, in terms of beta-lactam affinity and substrate hydrolysis, to altered PBP2x produced in resistant clinical isolates. A reverse mutation in a PBP2x variant from a clinically important resistant clone increases the acylation efficiency for beta-lactams and substrate analogues. Furthermore, amino acid residues in contact with the structural water molecule are conserved in the equivalent H-PBPs of pathogenic Gram-positive cocci. We suggest that, probably via a local structural modification, the partial or complete loss of this water molecule reduces the acylation efficiency of PBP2x substrates to a point at which cell wall synthesis still occurs, but the sensitivity to therapeutic concentrations of beta-lactam antibiotics is lost.

Amino Acid Substitution↗
PubMed1991

Multiple mechanisms regulate muscle fiber diversity.

Adult skeletal muscles are composed of clusters of multinucleated muscle cells called myofibers. At least three different types of myofibers can be detected within mammals based on their physiological properties and their expression of different contractile protein isoforms. Different skeletal muscles display a wide range of combinations of myofibers. Recent work has demonstrated that multiple mechanisms are responsible for the generation of these myofiber types during development. Muscle progenitor cells have been dissected into two categories on the basis of which isoforms of myosin heavy chain (MHC) they express when they differentiate. Neural and other environmental influences act to modify decisions concerning the type of contractile protein a myofiber may express, and this is most apparent for MHC. The other contractile protein gene families are initially regulated independent of the MHC gene family. One or more events late in development are responsible for coordinating isoform expression between the gene families to generate the adult phenotype. Studies of muscle gene expression have revealed that regulation can occur at the levels of transcription, alternative splicing of primary transcripts, mRNA stability, and translation. The current challenge is to decipher how environmental and functional information is interpreted in terms of the activity of the regulators of muscle gene expression.

Animals↗
PubMed1989

Structural basis of hierarchical multiple substates of a protein. I: Introduction.

A computer experiment of protein dynamics is carried out, which consists of two steps: (1) A Monte Carlo simulation of thermal fluctuations in the native state of a globular protein, bovine pancreatic trypsin inhibitor; and (2) a simulation of the quick freezing of fluctuating conformations into energy minima by minimization of the energy of a number of conformations sampled in the Monte Carlo simulation. From the analysis of results of the computer experiment is obtained the following picture of protein dynamics: multiple energy minima exist in the native state, and they are distributed in clusters in the conformational space. The dynamics has a hierarchical structure which has at least two levels. In the first level, dynamics is restricted within one of the clusters of minima. In the second, transitions occur among the clusters. Local parts of a protein molecule, side chains and local main chain segments, can take multiple locally stable conformations in the native state. Many minima result from combinations of these multiple local conformations. The hierarchical structure in the dynamics comes from interactions among the local parts. Protein molecules have two types of flexibility, each associated with elastic and plastic deformations, respectively.

Animals↗
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↗
PubMed2003

Clustering gene expression data using adaptive double self-organizing map.

This paper presents a novel clustering technique known as adaptive double self-organizing map (ADSOM). ADSOM has a flexible topology and performs clustering and cluster visualization simultaneously, thereby requiring no a priori knowledge about the number of clusters. ADSOM is developed based on a recently introduced technique known as double self-organizing map (DSOM). DSOM combines features of the popular self-organizing map (SOM) with two-dimensional position vectors, which serve as a visualization tool to decide how many clusters are needed. Although DSOM addresses the problem of identifying unknown number of clusters, its free parameters are difficult to control to guarantee correct results and convergence. ADSOM updates its free parameters during training, and it allows convergence of its position vectors to a fairly consistent number of clusters provided that its initial number of nodes is greater than the expected number of clusters. The number of clusters can be identified by visually counting the clusters formed by the position vectors after training. A novel index is introduced based on hierarchical clustering of the final locations of position vectors. The index allows automated detection of the number of clusters, thereby reducing human error that could be incurred from counting clusters visually. The reliance of ADSOM in identifying the number of clusters is proven by applying it to publicly available gene expression data from multiple biological systems such as yeast, human, and mouse. ADSOM's performance in detecting number of clusters is compared with a model-based clustering method.

Animals↗