Genome-Wide Profiling of Structural Genomic Variations in Korean HapMap Individuals

Background

Structural genomic variation study, along with microarray technology development has provided many genomic resources related with architecture of human genome, and led to the fact that human genome structure is a lot more complicated than previously thought.

Methodology/Principal Findings

In the case of International HapMap Project, Epstein-Barr various immortalized cell lines were preferably used over blood in order to get a larger number of genomic DNA. However, genomic aberration stemming from immortalization process, biased representation of the donor tissue, and culture process may influence the accuracy of SNP genotypes. In order to identify chromosome aberrations including loss of heterozygosity (LOH), large-scale and small-scale copy number variations, we used Illumina HumanHap500 BeadChip (555,352 markers) on Korean HapMap individuals (n = 90) to obtain Log R ratio and B allele frequency information, and then utilized the data with various programs including Illumina ChromoZone, cnvParition and PennCNV. As a result, we identified 28 LOHs (>3 mb) and 35 large-scale CNVs (>1 mb), with 4 samples having completely duplicated chromosome. In addition, after checking the sample quality (standard deviation of log R ratio <0.30), we selected 79 samples and used both signal intensity and B allele frequency simultaneously for identification of small-scale CNVs (<1 mb) to discover 4,989 small-scale CNVs. Identified CNVs in this study were successfully validated using visual examination of the genoplot images, overlapping analysis with previously reported CNVs in DGV, and quantitative PCR.

Conclusion/Significance

In this study, we describe the result of the identified chromosome aberrations in Korean HapMap individuals, and expect that these findings will provide more meaningful information on the human genome.     

Rapid MALDI biotyper-based identification and cluster analysis of <Emphasis Type="Italic">Streptococcus iniae</Emphasis>

Streptococcus iniae causes severe mortalities among cultured marine species, especially in the olive flounder (Paralichthys olivaceus), which is economically important in Korea and Japan. Recently, there has been growing concern regarding the emergence of S. iniae as a zoonotic pathogen. Here, 89 S. iniae isolates obtained from diseased olive flounders collected from 2003 to 2008 in Jeju Island, South Korea, were characterized using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The results were aligned both with the available Bruker Daltonics data-base and with a new set of S. iniae data entries developed in our laboratory, and the results were compared. When we used the Bruker Daltonics database, the 89 isolates yielded either “no reliable identification” or were incorrectly identified as Streptococcus pyogenes at the genus level. When we used the new data entries from our laboratory, in contrast, all of the isolates were correctly identified as S. iniae at the genus (100%) and species (96.6%) levels. We performed proteomic analysis, divided the 89 isolates into cluster I (51.7%), cluster II (20.2%), and cluster III (28.1%), and then used the MALDI Biotyper software to identify specific mass peaks that enabled discrimination between clusters and between Streptococcus species. Our results suggest that the use of MALDI TOF MS could outperform the conventional methods, proving easier, faster, cheaper and more efficient in properly identifying S. iniae. This strategy could facilitate the epidemiological and taxonomical study of this important fish pathogen.     

Polysaccharides isolated from liquid culture broth of <Emphasis Type="Italic">Inonotus obliquus</Emphasis> inhibit the invasion of human non-small cell lung carcinoma cells

Polysaccharides isolated from Inonotus obliquus (PLIO) have been known to have various pharmacological activities including antioxidant, immunostimulating and anti-tumor activity. However, the anti-metastatic effect of PLIO in human non-small cell lung carcinoma (NSCLC) has not been elucidated. In this study, we investigated the effects of PLIO on the metastatic potential of human NSCLC A549 cells and its underlying mechanisms. PLIO suppressed the invasive potential of A549 cells throughout reducing matrix metalloproteinase (MMP) expression. PLIO treatment inhibited NF-κB nuclear translocation in A549 cells. In addition, PLIO treatment inhibited the phosphorylation of JNK/AKT in A549 cells. These results suggest that PLIO could inhibit human NSCLC invasion via suppression of AKT/NF-κB signaling pathway.     

High-performance data mining with intelligent SSD

An intuitive way to process the big data efficiently is to reduce the volume of data transferred over the storage interface to a host system. This is the reason that the notion of intelligent SSD (iSSD) was proposed to give processing power to SSD. There is rich literature on iSSD, however, its real implementation has not been provided to the public yet. Most prior work aims to quantify the benefits of iSSD with analytical modeling. In this paper, we first develop on iSSD simulator and present the potential of iSSD in data mining through the iSSD simulator. Our iSSD simulator performs on top of the gem 5 simulator and fully simulates all the processes of data mining algorithms running in iSSD with cycle-level accuracy. Then, we further addresse how to exploit all the computing resources for efficient processing of data mining algorithms. These days, CPU, GPU, and SSD are recently equipped together in most computing environment. If SSD is replaced with iSSD later on, we have a new computing environment where the three computing resources collaborate one another to process big data quite effectively. For this, scheduling is required to decide which computing resource is going to run for which function at which time. In our heterogeneous scheduling, types of computing resources, memory sizes in computing resources, and inter-processor communication times including IO time in SSD are considered. Our scheduling results show that processing in the collaborative environment outperforms that in the traditional one by up to about 10 times.     

Deuteration of Escherichia coli Enzyme I alters its stability

Enzyme I^Ntr is the first protein in the nitrogen phosphotransferase pathway. Using an array of biochemical and biophysical tools, we characterized the protein, compared its properties to that of EI of the carbohydrate PTS and, in addition, examined the effect of substitution of all nonexchangeable protons by deuterium (perdeuteration) on the properties of EI^Ntr. Notably, we find that the catalytic function (autophosphorylation and phosphotransfer to NPr) remains unperturbed while its stability is modulated by deuteration. In particular, the deuterated form exhibits a reduction of approximately 4 °C in thermal stability, enhanced oligomerization propensity, as well as increased sensitivity to proteolysis in vitro. We investigated tertiary, secondary, and local structural changes, both in the absence and presence of PEP, using near- and far-UV circular dichroism and Trp fluorescence spectroscopy. Our data demonstrate that the aromatic residues are particularly sensitive probes for detecting effects of deuteration with an enhanced quantum yield upon PEP binding and apparent decreases in tertiary contacts for Tyr and Trp side chains. Trp mutagenesis studies showed that the region around Trp522 responds to binding of both PEP and NPr. The significance of these results in the context of structural analysis of EI^Ntr are evaluated.