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Dae-Won Kim

Publications and source records attributed to Dae-Won Kim.

16 recordsLinked to original sources
PubMed2006

Towards clustering of incomplete microarray data without the use of imputation.

MOTIVATION: Clustering technique is used to find groups of genes that show similar expression patterns under multiple experimental conditions. Nonetheless, the results obtained by cluster analysis are influenced by the existence of missing values that commonly arise in microarray experiments. Because a clustering method requires a complete data matrix as an input, previous studies have estimated the missing values using an imputation method in the preprocessing step of clustering. However, a common limitation of these conventional approaches is that once the estimates of missing values are fixed in the preprocessing step, they are not changed during subsequent processes of clustering; badly estimated missing values obtained in data preprocessing are likely to deteriorate the quality and reliability of clustering results. Thus, a new clustering method is required for improving missing values during iterative clustering process. RESULTS: We present a method for Clustering Incomplete data using Alternating Optimization (CIAO) in which a prior imputation method is not required. To reduce the influence of imputation in preprocessing, we take an alternative optimization approach to find better estimates during iterative clustering process. This method improves the estimates of missing values by exploiting the cluster information such as cluster centroids and all available non-missing values in each iteration. To test the performance of the CIAO, we applied the CIAO and conventional imputation-based clustering methods, e.g. k-means based on KNNimpute, for clustering two yeast incomplete data sets, and compared the clustering result of each method using the Saccharomyces Genome Database annotations. The clustering results of the CIAO method are more significantly relevant to the biological gene annotations than those of other methods, indicating its effectiveness and potential for clustering incomplete 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.

Algorithms↗
PubMed2006

PLPD: reliable protein localization prediction from imbalanced and overlapped datasets.

Subcellular localization is one of the key functional characteristics of proteins. An automatic and efficient prediction method for the protein subcellular localization is highly required owing to the need for large-scale genome analysis. From a machine learning point of view, a dataset of protein localization has several characteristics: the dataset has too many classes (there are more than 10 localizations in a cell), it is a multi-label dataset (a protein may occur in several different subcellular locations), and it is too imbalanced (the number of proteins in each localization is remarkably different). Even though many previous works have been done for the prediction of protein subcellular localization, none of them tackles effectively these characteristics at the same time. Thus, a new computational method for protein localization is eventually needed for more reliable outcomes. To address the issue, we present a protein localization predictor based on D-SVDD (PLPD) for the prediction of protein localization, which can find the likelihood of a specific localization of a protein more easily and more correctly. Moreover, we introduce three measurements for the more precise evaluation of a protein localization predictor. As the results of various datasets which are made from the experiments of Huh et al. (2003), the proposed PLPD method represents a different approach that might play a complimentary role to the existing methods, such as Nearest Neighbor method and discriminate covariant method. Finally, after finding a good boundary for each localization using the 5184 classified proteins as training data, we predicted 138 proteins whose subcellular localizations could not be clearly observed by the experiments of Huh et al. (2003).

Algorithms↗
PubMed2006

Human chromosome 11 DNA sequence and analysis including novel gene identification.

Chromosome 11, although average in size, is one of the most gene- and disease-rich chromosomes in the human genome. Initial gene annotation indicates an average gene density of 11.6 genes per megabase, including 1,524 protein-coding genes, some of which were identified using novel methods, and 765 pseudogenes. One-quarter of the protein-coding genes shows overlap with other genes. Of the 856 olfactory receptor genes in the human genome, more than 40% are located in 28 single- and multi-gene clusters along this chromosome. Out of the 171 disorders currently attributed to the chromosome, 86 remain for which the underlying molecular basis is not yet known, including several mendelian traits, cancer and susceptibility loci. The high-quality data presented here--nearly 134.5 million base pairs representing 99.8% coverage of the euchromatic sequence--provide scientists with a solid foundation for understanding the genetic basis of these disorders and other biological phenomena.

Chromosomes, Human, Pair 11↗
PubMed2006

Successful whole blood exchange by apheresis in a patient with acute cyclosporine intoxication without long-term sequelae.

Acute cyclosporine A (CsA) intoxication after organ transplantation may occur during the changeover from one form of drug to another, or from miscalculation of dosage. Sometimes, it may cause severe hepatotoxicity, nephrotoxicity and neurotoxicity. However, the therapeutic plasma exchange for the CsA intoxication was not established. Here, we present a case of very severe CsA intoxication after cardiac transplantation who recovered from intoxication without long-term sequelae via whole blood exchange; therapeutic erythrocytapheresis followed by total plasma exchange.

Blood Component Removal↗
PubMed2006

Comparative genomic organization of the human and bovine PRNP locus.

We sequenced a 208-kb BAC clone spanning the bovine prion protein (PRNP) locus, and compared the genomic structure with that of human. As a result, we determined the precise breakpoint between the two syntenic genomes, located on the 5' UTR of the PRNP gene, and discovered two highly repetitive sequences near the breakpoint. Further analysis demonstrated that the genomic structure of three genes, PRNP, PRND, and RASSF2, within the syntenic region of the bovine genome is highly conserved in order and orientation. The PRNT locus was not found in bovine but is conserved in several primates, including human. Moreover, we confirmed that the bovine RASSF2 is composed of 10 exons, as is the human gene, showing some difference from a previous report. Our findings may provide useful clues for understanding the evolutional process in the PRNP locus and also the mechanism that allows TSE from cattle to infect humans.

Amyloid↗
PubMed2006

Nkx3.2/Bapx1 acts as a negative regulator of chondrocyte maturation.

Parathyroid hormone-related protein (PTHrP) is essential to maintain a pool of dividing, immature chondrocytes in the growth plate of long bones. In chick and mouse, expression of Nkx3.2/Bapx1 in the growth plate is restricted to the proliferative zone and is down regulated as chondrocyte maturation begins. Nkx3.2/Bapx1 expression is lost in the growth plates of mice engineered to lack PTHrP signaling and, conversely, is maintained by ectopic expression of PTHrP in developing bones. Artificially preventing Nkx3.2/Bapx1 downregulation, by forced expression of either retroviral-encoded PTHrP or Nkx3.2 inhibits chondrocyte maturation. Although wild-type Nkx3.2 blocks chondrocyte maturation by acting as a transcriptional repressor, a ;reverse function' mutant of Nkx3.2 that has been converted into a transcriptional activator conversely accelerates chondrocyte maturation. Nkx3.2 represses expression of the chondrocyte maturation factor Runx2, and Runx2 mis-expression can rescue the Nkx3.2-induced blockade of chondrocyte maturation. Taken together, these results suggest that PTHrP signals block chondrocyte hypertrophy by, in part, maintaining the expression of Nkx3.2/Bapx1, which in turn represses the expression of genes required for chondrocyte maturation.

Animals↗
PubMed2006

Comparative analysis of chimpanzee and human Y chromosomes unveils complex evolutionary pathway.

The mammalian Y chromosome has unique characteristics compared with the autosomes or X chromosomes. Here we report the finished sequence of the chimpanzee Y chromosome (PTRY), including 271 kb of the Y-specific pseudoautosomal region 1 and 12.7 Mb of the male-specific region of the Y chromosome. Greater sequence divergence between the human Y chromosome (HSAY) and PTRY (1.78%) than between their respective whole genomes (1.23%) confirmed the accelerated evolutionary rate of the Y chromosome. Each of the 19 PTRY protein-coding genes analyzed had at least one nonsynonymous substitution, and 11 genes had higher nonsynonymous substitution rates than synonymous ones, suggesting relaxation of selective constraint, positive selection or both. We also identified lineage-specific changes, including deletion of a 200-kb fragment from the pericentromeric region of HSAY, expansion of young Alu families in HSAY and accumulation of young L1 elements and long terminal repeat retrotransposons in PTRY. Reconstruction of the common ancestral Y chromosome reflects the dynamic changes in our genomes in the 5-6 million years since speciation.

Animals↗
PubMed2006

Epileptogenic roles of astroglial death and regeneration in the dentate gyrus of experimental temporal lobe epilepsy.

Recent studies have demonstrated that blockade of neuronal death in the hippocampus cannot prevent epileptogenesis in various epileptic models. These reports indicate that neurodegeneration alone is insufficient to cause epilepsy, and that the role of astrocytes in epileptogenesis should be reconsidered. Therefore, the present study was designed to elucidate whether altered morphological organization or the functionalities of astrocytes induced by status epilepticus (SE) is responsible for epileptogenesis. Glial responses (reactive microgliosis followed by astroglial death) in the dentate gyrus induced by pilocarpine-induced SE were found to precede neuronal damage and these alterations were closely related to abnormal neurotransmission related to altered vesicular glutamate and GABA transporter expressions, and mossy fiber sprouting in the dentate gyrus. In addition, newly generated astrocytes showed down-regulated expressions of glutamine synthase, glutamate dehydrogenase, and glial GABA transporter. Taken together, our findings suggest that glial responses after SE may contribute to epileptogenesis and the acquisition of the properties of the epileptic hippocampus. Thus, we believe that it is worth considering new therapeutic approaches to epileptogenesis involving targeting the inactivation of microglia and protecting against astroglial loss.

Animals↗
PubMed2005

Identification of novel allele on the locus 47z (DXYS5) in the Korean population.

Two homogenous sequences of 47z (DXYS5) are located on the X (DXYS5X) and Y (DXYS5Y) chromosomes, and these are known to be useful polymorphic markers for tracing male-specific gene flow such as the migration routes of human populations. Using the 47z/StuI PCR-RFLP system, we found a novel allele which showed two bands, in contrast to the previous two allele types, one band (Y1) and three bands (Y2). This means that copies of PCR products derived from both the DXYS5X and DXYS5Y loci were clearly cut by the StuI enzyme, implying that the DXYS5X locus of the X chromosome is polymorphic. Allelic frequencies examined in 267 male Korean individuals showed that 95.8% had Y1, 3.4% Y2, and 0.8% had the novel allele. Our findings should contribute to a better understanding of genetic polymorphism on X and Y chromosomes, the molecular evolution mechanism of sex chromosomes, and how the migration route of Koreans is related to those of other East Asian populations.

Base Sequence↗
PubMed2005

mu-Calpain regulates receptor activator of NF-kappaB ligand (RANKL)-supported osteoclastogenesis via NF-kappaB activation in RAW 264.7 cells.

To clarify the role of calpain in the receptor activator of NF-kappaB ligand (RANKL)-supported osteoclastogenesis, RANKL-induced calpain activation was examined by using murine RAW 264.7 cells and bone marrow-derived monocyte/macrophage progenitors. We found that calpain activity increased in response to RANKL in both cell types based on alpha-spectrinolysis and that mu-calpain, rather than m-calpain, was activated during RANKL-supported osteoclastogenesis in RAW 264.7 cells. Overexpression of mu-calpain clearly augmented RANKL-supported osteoclastogenesis in RAW 264.7 cells, thereby implicating its pivotal role in this process. Cell-permeable calpain inhibitors, including calpastatin and calpeptin, were sufficient to suppress RANKL-supported osteoclastogenesis based on decreased expression of the osteoclastogenic marker, matrix metalloproteinase 9, and the generation of tartrate-resistant acid phosphatase-positive multinucleated cells in both cell types. Calpain inhibitors suppressed NF-kappaB activation via inhibition of the cleavage of inhibitor of NF-kappaB(IkappaBalpha)in RAW 264.7 cells. Taken together, our findings suggest that mu-calpain is essential to the regulation of RANKL-supported osteoclastogenesis via NF-kappaB activation.

Animals↗
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↗
PubMed2005

Autologous peripheral blood stem cell collections in children weighing less than 10 Kg with solid tumors: experience of a single center.

There have only been a few reports and limited performance of peripheral blood stem cell (PBSC) collection in very small children weighing less than 10 kg. In this study, we intended to evaluate the safety and yield of PBSC collection, with the efficacy of PBSC transplantation (PBSCT) in the smallest children with solid tumors. From January 1998 to February 2004, 173 children underwent PBSC collection in Samsung Medical Center, Korea. Of these, 15 (8.7%) children weighed less than 10 kg and their clinical diagnoses were neuroblastoma (10 cases), rhabdoid tumor (2 cases), rhabdomyosarcoma (2 cases), and Wilms tumor (1 case). PBSCs were collected following chemotherapy plus G-CSF mobilization. The median age and weight at the time of apheresis were 15 months and 9 kg, respectively. The median number of PBSC collection procedures per case was 4 (range, 2-7). The median cell yield per apheresis product was 0.95 (range, 0.01-33.32) x 10(6)/kg CD34+ cells and 1.96 (range, 0.12-23.39) x 10(8)/kg mononuclear cells. No complications associated with citrate toxicity and other adverse effect were observed during the procedures. After high-dose chemotherapy, 14 patients were reinfused with PBSCs alone and all showed successful hematopoietic recovery. We concluded that PBSC collection would be a safe and practical procedure, even when done in the smallest children, provided that adequate intravascular fluid volume and circulating red cell mass were maintained. Also, the use of PBSCs to support high-dose chemotherapy was well tolerated and might enhance hematological recovery in the smallest children showing the excellent efficacy of PBSCT.

Cell Separation↗
PubMed2004

Increased expression of antioxidant enzymes in radioresistant variant from U251 human glioblastoma cell line.

Glioblastoma is one of the most radioresistant tumors. Exposure of cells to ionizing radiation leads to formation of reactive oxygen species (ROS) that are associated with radiation-induced cytotoxicity. ROS scavengers, therefore, are one of the important factors in protecting cells against ROS injury during ionizing radiation exposure. In the present study, we isolated and established a radioresistant variant clone (RRC) from U251 human glioblastoma cell line and investigated the potential role of antioxidant enzymes in radioresistance of the glioblastoma cell line. RRC showed a higher radioresistance than the parent cell line as measured by clonogenic survival assay and showed delayed G2/M arrest. Antioxidant enzymes, such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPX), glutathione reductase (GR), were activated up to 5-fold in RRC compared to the parent cells after radiation. In addition, RRC also had cross-resistance to the antitumor agent cisplatin. Therefore, radioresistance and cross-resistance to chemotherapeutic agent in RRC might be due to the highly coordinated activation of antioxidant enzymes rather than a single enzyme alone.

Antioxidants↗
PubMed2003

Characterization of Nkx3.2 DNA binding specificity and its requirement for somitic chondrogenesis.

We have previously shown that Nkx3.2, a member of the NK class of homeoproteins, functions as a transcriptional repressor to promote somitic chondrogenesis. However, it has not been addressed whether Nkx3.2 can bind to DNA in a sequence-specific manner and whether DNA binding by Nkx3.2 is required for its biological activity. In this work, we employed a DNA binding site selection assay, which identified TAAGTG as a high affinity Nkx3.2 binding sequence. Sequence-specific binding of Nkx3.2 to the TAAGTG motif in vitro was confirmed by electrophoretic mobility shift assays, and mutagenesis of this sequence revealed that HRAGTG (where H represents A, C, or T, and R represents A or G) comprises the consensus DNA binding site for Nkx3.2. Consistent with these findings, the expression of a reporter gene containing reiterated Nkx3.2 binding sites was repressed in vivo by Nkx3.2 co-expression. In addition, we have generated a DNA nonbinding point mutant of Nkx3.2 (Nkx3.2-N200Q), which contains an asparagine to glutamine missense mutation in the homeodomain. Interestingly, despite being defective in DNA binding, Nkx3.2-N200Q still retains its intrinsic transcriptional repressor function. Finally, we demonstrate that unlike wild-type Nkx3.2, Nkx3.2-N200Q is unable to activate the chondrocyte differentiation program in somitic mesoderm, indicating that DNA binding by Nkx3.2 is critical for this factor to induce somitic chondrogenesis.

3T3 Cells↗
PubMed2003

Smad-dependent recruitment of a histone deacetylase/Sin3A complex modulates the bone morphogenetic protein-dependent transcriptional repressor activity of Nkx3.2.

We have previously shown that Nkx3.2, a transcriptional repressor that is expressed in the sclerotome and developing cartilage, can activate the chondrocyte differentiation program in somitic mesoderm in a bone morphogenetic protein (BMP)-dependent manner. In this work, we elucidate how BMP signaling modulates the transcriptional repressor activity of Nkx3.2. We have found that Nkx3.2 forms a complex, in vivo, with histone deacetylase 1 (HDAC1) and Smad1 and -4 in a BMP-dependent manner. The homeodomain and NK domain of Nkx3.2 support the interaction of this transcription factor with HDAC1 and Smad1, respectively, and both of these domains are required for the transcriptional repressor activity of Nkx3.2. Furthermore, the recruitment of an HDAC/Sin3A complex to Nkx3.2 requires that Nkx3.2 interact with Smad1 and -4. Indeed, Nkx3.2 both fails to associate with the HDAC/Sin3A complex and represses target gene transcription in a cell line lacking Smad4, but it performs these functions if exogenous Smad4 is added to these cells. While prior work has indicated that BMP-dependent Smads can support transcriptional activation, our findings indicate that BMP-dependent Smads can also potentiate transcriptional repression, depending upon the identity of the Smad-interacting transcription factor.

Animals↗