Superparamagnetic Clustering of Data

Blatt, Marcelo; Wiseman, Shai; Domany, Eytan

doi:10.1103/physrevlett.76.3251

Cited by 480 publications

(521 citation statements)

References 14 publications

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“…With the fraction of the sequences in the subalignment set to f =0.35 (see Methods) in the SCA, there are 74 allowed perturbations (S j = 0 for j = 1, 2, 3...74) at the various positions in the DHFR family. We used the clustering protocol [42,43] to identify the set of co-varying residues. After rescaling the ∆∆G ij matrix (Eq.…”

Section: Resultsmentioning

confidence: 99%

Allosteric Communication in Dihydrofolate Reductase: Signaling Network and Pathways for Closed to Occluded Transition and Back

Chen

Dima

Thirumalai

2007

Journal of Molecular Biology

113

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1 Abstract E. Coli. dihydrofolate reductase (DHFR) catalyzes the reduction of dihydrofolate to tetrahydrofolate.During the catalytic cycle, DHFR undergoes conformational transitions between the closed (CS) and occluded (OS) states which, respectively, describe whether the active site is closed or occluded by the Met20 loop. The CS→OS and the reverse transition may be viewed as allosteric transitions.Using a sequence-based approach we identify a network of residues that represents the allostery wiring

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Section: Resultsmentioning

confidence: 99%

Allosteric Communication in Dihydrofolate Reductase: Signaling Network and Pathways for Closed to Occluded Transition and Back

Chen

Dima

Thirumalai

2007

Journal of Molecular Biology

113

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“…The super paramagnetic clustering (SPC) algorithm 16 was used for performing cluster analysis. In the resulting dendrogram (Figure 1), stable (i.e., statistically significant) gene clusters are identified; these are denoted G2-G12 (see Supplementary Information for the complete list of genes in each cluster).…”

Section: Clustering Analysismentioning

confidence: 99%

TGFβ-dependent gene expression profile during maturation of dendritic cells

et al. 2007

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Primary immune response to pathogens involves the maturation of antigen-presenting dendritic cells (DC). Bacterial lipopolysacharride (LPS) is a potent inducer of DC maturation, whereas the transforming growth factor b (TGFb) attenuates much of this process. Here, we analyzed the global gene expression pattern in LPS-treated bone marrow derived DC during inhibition of their maturation process by TGFb. Exposure of DC to LPS induces a pronounced cell response, manifested in altered expression of a large number of genes. Interestingly, TGFb did not affect most of the LPS responding genes. Nevertheless, analysis identified a subset of genes that did respond to TGFb, among them the two inflammatory cytokines interleukin (IL)-12 and IL-18. Expression of IL-12, the major proinflammatory cytokine secreted by mature DC, was downregulated by TGFb, whereas the expression level of the proinflammatory cytokine IL-18, known to potentiate the IL-12 effect, was upregulated. Expression of the peroxisome proliferator-activated receptor g (PPARg) increased in response to TGFb, concomitantly with reduced expression of chemokine receptor 7 (CCR7). This finding supports the possibility that TGFbdependent inhibition of CCR7 expression in DC is mediated by PPARg.

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“…Clustering DNA chip data by means of the SPC algorithm (Blatt et al, 1996) is an unsupervised approach that aims at finding groups of genes with similar expression profiles (Kannan et al, 2001). Applying this method to the 573 genes identified in NHEK (Figure 4a) revealed a clear-cut partitioning/ distinction between up-and downregulated ones (Figure 5a).…”

Section: Cluster Analysismentioning

confidence: 99%

Genome-wide comparison of human keratinocyte and squamous cell carcinoma responses to UVB irradiation: implications for skin and epithelial cancer

et al. 2003

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To gain insight into the transformation of epidermal cells into squamous carcinoma cells (SCC), we compared the response to ultraviolet B radiation (UVB) of normal human epidermal keratinocytes (NHEK) versus their transformed counterpart, SCC, using biological and molecular profiling. DNA microarray analyses (Affymetrix s , B12 000 genes) indicated that the major group of upregulated genes in keratinocytes fall into three categories: (i) antiapoptotic and cell survival factors, including chemokines of the CXC/CC subfamilies (e.g. IL-8, GRO-1, -2, -3, SCYA20), growth factors (e.g. HB-EGF, CTGF, INSL-4), and proinflammatory mediators (e.g. COX-2, S100A9), (ii) DNA repair-related genes (e.g. GADD45, ERCC, BTG-1, Histones), and (iii) ECM proteases (MMP-1, -10). The major downregulated genes are DNp63 and PUMILIO, two potential markers for the maintenance of keratinocyte stem cells. NHEK were found to be more resistant than SCC to UVB-induced apoptosis and this resistance was mainly because of the protection from cell death by secreted survival factors, since it can be transferred from NHEK to SCC cultures by the conditioned medium. Whereas the response of keratinocytes to UVB involved regulation of key checkpoint genes (p53, MDM2, p21 Cip1 , DNp63), as well as antiapoptotic and DNA repair-related genes -no or little regulation of these genes was observed in SCC. The effect of UVB on NHEK and SCC resulted in upregulation of 251 and 127 genes, respectively, and downregulation of 322 genes in NHEK and 117 genes in SCC. To further analyse these changes, we used a novel unsupervised coupled two-way clustering method that allowed the identification of groups of genes that clearly partitioned keratinocytes from SCC, including a group of genes whose constitutive expression levels were similar before UVB. This allowed the identification of discriminating genes not otherwise revealed by simple static comparison in the absence of UVB irradiation. The implication of the changes in gene profile in keratinocytes for epithelial cancer is discussed.

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Superparamagnetic Clustering of Data

Cited by 480 publications

References 14 publications

Allosteric Communication in Dihydrofolate Reductase: Signaling Network and Pathways for Closed to Occluded Transition and Back

Allosteric Communication in Dihydrofolate Reductase: Signaling Network and Pathways for Closed to Occluded Transition and Back

TGFβ-dependent gene expression profile during maturation of dendritic cells

Genome-wide comparison of human keratinocyte and squamous cell carcinoma responses to UVB irradiation: implications for skin and epithelial cancer

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