Core Clustering Research Articles

Unsupervised Selection of Highly Coexpressed and Noncoexpressed Genes Using a Consensus Clustering Approach

In this paper we explore the concept of consensus clustering to identify, within a set of differentially expressed genes, a subset of genes that are either highly coexpressed or highly noncoexpressed based on the hypothesis that this subset would serve as a better starting point for further analyses. A number of core clustering methods form the basis for the assertion of an agreement matrix (AM) characterizing the level of coexpression between any two probesets. In order to overcome the limitations of using a single distance metric, we explore different metrics and examine the sensitivity of the AM as a function of the input number of clusters to find a suggestive number of clusters that best describes a particular dataset. The result of this level of analysis is a systematic framework for eliminating probesets that cannot be clearly characterized as either coexpressed or noncoexpressed with others, thus eliminating a number of probesets from further analysis. Subsequently, an agglomerative hierarchical clustering approach is applied to cluster the selected subset using the agreement metric information as the similarity measure. Thus, the goal of the proposed methodology is twofold: (1) we opt to identify a more "clusterable" subset of the original set; and (2) we aim at further refining the subset in order to identify a core of genes that contains genes that are either coexpressed or noncoexpressed within a certain confidence level. The approach is tested with a number of data sets, both synthetic and real, and it is demonstrated that it is successful in identifying more clusterable, also hypothesized to be more biologically relevant, subsets of genes and expression profiles.

Competitive Repetition Suppression (CoRe) Clustering: A Biologically Inspired Learning Model With Application to Robust Clustering

Determining a compact neural coding for a set of input stimuli is an issue that encompasses several biological memory mechanisms as well as various artificial neural network models. In particular, establishing the optimal network structure is still an open problem when dealing with unsupervised learning models. In this paper, we introduce a novel learning algorithm, named competitive repetition-suppression (CoRe) learning, inspired by a cortical memory mechanism called repetition suppression (RS). We show how such a mechanism is used, at various levels of the cerebral cortex, to generate compact neural representations of the visual stimuli. From the general CoRe learning model, we derive a clustering algorithm, named CoRe clustering, that can automatically estimate the unknown cluster number from the data without using a priori information concerning the input distribution. We illustrate how CoRe clustering, besides its biological plausibility, posses strong theoretical properties in terms of robustness to noise and outliers, and we provide an error function describing CoRe learning dynamics. Such a description is used to analyze CoRe relationships with the state-of-the art clustering models and to highlight CoRe similitude with rival penalized competitive learning (RPCL), showing how CoRe extends such a model by strengthening the rival penalization estimation by means of loss functions from robust statistics.

Design of a wireless test control network with radio-on-chip technology for nanometer system-on-a-chip

The continued push to smaller geometries, higher frequencies, and larger chip sizes rapidly resulted in an incompatibility between interconnect needs and projected interconnect performance. As stated in the 2003 International Technology Roadmap for Semiconductors (ITRS'03) report, revolutionary interconnect methodologies such as radio frequency (RF)/wireless will deliver the foreseen progress in semiconductor technology. Recent advances in silicon integrated circuit technique are making possible tiny low-cost transceivers to be integrated on chip, namely radio-on-chip (ROC) technology. This paper proposes the idea of using wireless radios to transmit test data and control signals to resolve the acerbated core accessibility problem. Three types of wireless test micronetworks are first presented, i.e., miniature wireless local area network (LAN), multihop wireless test control network (MTCNet), and distributed multihop MTCNet. Then, the test control overhead and system resource partitioning in on-chip wireless micronetworks are analyzed. Several challenging system design problems such as RF node placement, core clustering, and control routing are studied, and the test control resources (i.e., the on-chip RF nodes for intrachip communication) are properly distributed and system optimization is performed in terms of test control cost. A simulation study shows the feasibility and applicability of intrachip MTCNet

Variable LH2 stoichiometry and core clustering in native membranes of Rhodospirillum photometricum.

The individual components of the photosynthetic unit (PSU), the light-harvesting complexes (LH2 and LH1) and the reaction center (RC), are structurally and functionally known in great detail. An important current challenge is the study of their assembly within native membranes. Here, we present AFM topographs at 12 A resolution of native membranes containing all constituents of the PSU from Rhodospirillum photometricum. Besides the major technical advance represented by the acquisition of such highly resolved data of a complex membrane, the images give new insights into the organization of this energy generating apparatus in Rsp. photometricum: (i) there is a variable stoichiometry of LH2, (ii) the RC is completely encircled by a closed LH1 assembly, (iii) the LH1 assembly around the RC forms an ellipse, (iv) the PSU proteins cluster together segregating out of protein free lipid bilayers, (v) core complexes cluster although enough LH2 are present to prevent core-core contacts, and (vi) there is no cytochrome bc1 complex visible in close proximity to the RCs. The functional significance of all these findings is discussed.

Clustering of Large Hydrophobes in the Hydrophobic Core of Two-stranded α-Helical Coiled-Coils Controls Protein Folding and Stability

The de novo design and biophysical characterization of two 60-residue peptides that dimerize to fold as parallel coiled-coils with different hydrophobic core clustering is described. Our goal was to investigate whether designing coiled-coils with identical hydrophobicity but with different hydrophobic clustering of non-polar core residues (each contained 6 Leu, 3 Ile, and 7 Ala residues in the hydrophobic core) would affect helical content and protein stability. The disulfide-bridged P3 and P2 differed dramatically in alpha-helical structure in benign conditions. P3 with three hydrophobic clusters was 98% alpha-helical, whereas P2 was only 65% alpha-helical. The stability profiles of these two analogs were compared, and the enthalpy and heat capacity changes upon denaturation were determined by measuring the temperature dependence by circular dichroism spectroscopy and confirmed by differential scanning calorimetry. The results showed that P3 assembled into a stable alpha-helical two-stranded coiled-coil and exhibited a native protein-like cooperative two-state transition in thermal melting, chemical denaturation, and calorimetry experiments. Although both peptides have identical inherent hydrophobicity (the hydrophobic burial of identical non-polar residues in equivalent heptad coiled-coil positions), we found that the context dependence of an additional hydrophobic cluster dramatically increased stability of P3 (Delta Tm approximately equal to 18 degrees C and Delta[urea](1/2) approximately equal to 1.5 M) as compared with P2. These results suggested that hydrophobic clustering significantly stabilized the coiled-coil structure and may explain how long fibrous proteins like tropomyosin maintain chain integrity while accommodating polar or charged residues in regions of the protein hydrophobic core.

Association of the core clustering mutations (codon 21-34) and the severity of chronic hepatitis B in Korean patients.

Objectives:There are regions in the core gene of hepatitis B virus (HBV) where missense mutations are clustered, and mutations in that region are related to severe liver disease. However, there were some differences of the major regions for mutation clustering among ethnic groups. To explore the phenomenon of clustering mutations in Korean patients with chronic HBV infection and to elucidate the correlation between clustering mutation region of the core gene and the severity of liver damage, we analyzed the precore/core gene sequence of HBV in the sera from fifteen chronic hepatitis B (CH-B) patients.Methods:We analysed the HBV precore and core sequences in the sera obtained from fifteen patients (14 males and 1 female, mean age 30.0 years) with biopsy-proven CH-B. The patients were divided into two groups according to the pathological severity of CH-B; namely, group I consisted of 8 patients with chronic persistent hepatitis (CPH), and group II included 7 patients with chronic active hepatitis (CAH). After extraction of HBV DNA from each serum by proteinase K and phenol-chloroform solution, the entire precore and core region of HBV was amplified by PCR, and then the PCR products were subjected to direct sequencing using thermostable DNA polymerase. Fisher’s exact test and Mann-Whitney U test were used for statistical analysis.Results:A total of 181 nucleotide substitutions were found in the HBV core gene from the 15 CH-B patients, of which 23 were missense and 158 were silent. The nucleotide and amino acid substitution rates were not significantly different between the two groups (p>0.05). Two mutational hot spots (MHS), codons 21–34 (MHS1) and codons 85–100 (MHS2), were found in the deduced amino acid alignment of the core gene. The alteration rate of amino acid residue in these regions were 2.857×10−2 and 5.000×10−2, respectively. Of 8 CPH patients, 5 showed missense mutations only in MHS2. In comparison, of 7 CAH patients, 3 showed them both in MHS1 and MHS2, 1 only in MHS1, and 1 only in MHS2; thus, missense mutation in MHS1 was exclusively found in patient with CAH.Conclusions:There were two mutation clusterings in the core region of adr subtype of HBV from Korean CH-B patients. Mutations in MHS1 (codon 21–34), but not in MHS2 (codon 85–100), are more likely to be related to the severity of CH-B. A longitudinal study using sequential samples is warranted to further clarify the role of MHS1 in the pathogenesis of more severe CH-B.

Precore mutations and core clustering mutations in chronic hepatitis B virus infection

Background: Mutant hepatitis B virus is often associated with severe liver damage. The purpose of this study is to elucidate the relationship between mutations in hepatitis B precore/core gene and the severity of liver damage. Methods: The hepatitis B precore/ core gene from 20 patients with chronic hepatitis B virus infection was studied by polymerase chain reaction and direct sequencing. Results: Missense mutations in the core gene were only found in patients with chronic active hepatitis. Three mutation clustering regions of core gene, codons 48–60, 84–101, and 147–155, had higher substitution rates than other regions. All patients with chronic active hepatitis had missense mutation(s) either in codons 84–101 or in codons 48–60. There was a trend of increasing substitutions in the precore/core gene from e antigenpositive asymptomatic carriers to e antibody-positive patients with chronic active hepatitis. Conclusions: These data suggest that (1) severe liver damage in chronic hepatitis B virus infection is related to the clustering missense mutations in codons 48–60 and 84–101 of core gene and that (2) the emergence of precore stop codon mutation and missense mutations around the carboxy-terminal processing site of precore/core protein (codons 147–155) may be the adaptive mechanisms of hepatitis B virus to decrease production and secretion of viral protein and retain the viral persistence.

X-ray observations of 20 3CR radio galaxies and their environs

X-ray observations of 20 3CR radio galaxies using the Imaging Proportional Counter on the Einstein Observatory are reported. Fourteen of the 18 galaxies, plus two sources without optical identification, are detected with soft X-ray luminosities (Lx) ranging from 10 to the 40.9th to 10 to the 44.4th ergs/s. In four of the galaxies there is evidence for extended X-ray structure. Lx is statistically correlated with the radio power of the core, the lobe radio power (especially below 1 GHz), and the steepness of the lobe radio spectrum at high frequencies. The complex interrelations between X-ray luminosities and radio core, radio lobe, optical nuclei, and galaxy clustering are examined; and it is found that a cluster origin of the X-rays provides the best explanation of these effects. Constraints on synchrotron and inverse Compton production of X-rays in radio lobes and on mechanisms of lobe confinement are also discussed.

Elastic core effect and clustering tendency by EXAFS in as-quenched Al-Zn alloys

Random distributions of solute atoms are observed for as-quenched solid solutions for concentrations of zinc up to 2.6 at.%. For Al-4.4 at.% Zn or Al-6.8 at.% Zn, evidence of clustering effects is observed: the first peak of the Fourier transform of the spectrum is reduced to 73% and 47% respectively by the mixing of Al and Zn backscatterers in the nearest-neighbour shell. For the as-quenched Al-4.4 at.% Zn, 1.5 (+or-0.25) zinc atoms are present among the twelve atoms of the first shell and 3.25 (+or-0.25) zinc atoms for Al-6.8 at.% Zn. As for Al-Cu, it has been possible to determine the magnitude of the 'elastic core effect' (strain on the first shell) in dilute solutions. As expected, this effect is weak, db approximately=-0.02+or-0.01 AA, where 'b' is the radius of the first shell in aluminium. Nevertheless, it is about three times higher than the calculated value derived from the slope of Vegard's law (da/ac=-0.020) throughout an elastic theory of a continuous medium.

Microscopic first-order core polarization corrections to dwba for (p, p') scattering

The importance of full antisymmetrization (taking also into account the exchange nature of the nuclear forces), and first-order corrections to the DWBA matrix element are examined in the case of (p, p') and nuclei with two identical particles outside closed shells. These corrections correspond to core polarization and clustering of the projectile with the valence particles. We considered, as examples 18O, 54Fe, 90Zr and 206Pb. The results indicate an increase by a factor 2–10 in the cross-section normalization if all contributions are added, whereas, the angular distribution is practically insensitive to the various corrections. The agreement with experiment is fair for the angular distributions, but off about a factor 4 or more in the crosssection normalization.