Center for Genome Science

Science, South Korea

Center for Genome Science

Science, South Korea
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Ali J.,Center for Genome science | Sabiha B.,Center for Genome science | Jan H.U.,Center for Genome science | Haider S.A.,Center for Genome science | And 2 more authors.
Oral Oncology | Year: 2017

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. It accounts for 2.5% of all new cancer cases and 1.9% of all cancer deaths annually. More than 90% of oral cancers (occurring in the mouth, lip, and tongue) are oral squamous cell carcinoma. The incidence rate of oral cancer varies widely throughout the world, with an evident prevalence in South Asian countries. This high incidence occurs in correlation with oral cancer-associated behaviors such as alcohol, tobacco use. Researchers have reported that these behaviors lead to genetic variations in tumor suppressor genes (APC, p53), proto-oncogenes (Myc), oncogene (Ras) and genes controlling normal cellular processes (EIF3E, GSTM1). Processes such as segregation of chromosomes, genomic copy number, loss of heterozygosity, telomere stabilities, regulations of cell-cycle checkpoints, DNA damage repairs and defects in notch signaling pathways are involved in causing oral cancer. In order to develop preventive and therapeutic options, it is necessary to comprehend the basic molecular mechanisms forcing oral tumorigenesis. This review examines, in detail, the mechanisms of genetic alteration which are considered to be responsible for the initiation of oral cancer. © 2017 Elsevier Ltd

PubMed | University of Michigan, Pacific Biosciences, Center for Genome science, University of Florida and 3 more.
Type: Journal Article | Journal: mBio | Year: 2016

Whole-genome sequence (WGS) data are commonly used to design diagnostic targets for the identification of bacterial pathogens. To do this effectively, genomics databases must be comprehensive to identify the strict core genome that is specific to the target pathogen. As additional genomes are analyzed, the core genome size is reduced and there is erosion of the target-specific regions due to commonality with related species, potentially resulting in the identification of false positives and/or false negatives.A comparative analysis of 1,130 Burkholderia genomes identified unique markers for many named species, including the human pathogens B.pseudomallei and B.mallei Due to core genome reduction and signature erosion, only 38 targets specific to B.pseudomallei/mallei were identified. By using only public genomes, a larger number of markers were identified, due to undersampling, and this larger number represents the potential for false positives. This analysis has implications for the design of diagnostics for other species where the genomic space of the target and/or closely related species is not well defined.

PubMed | Centers for Disease Control and Prevention, University of Federal Defense Munich, Charles Darwin University, Center for Genome science and 2 more.
Type: | Journal: Applied and environmental microbiology | Year: 2016

During routine screening for endemic Burkholderia pseudomallei from water wells in northern Australia, Gram-staining-negative bacteria (strains MSMB43Burkholderia pseudomallei is a soil dwelling bacteria and the causative agent of melioidosis. The genus Burkholderia consists of a diverse group of species with the closest relatives of B. pseudomallei referred to as the B. pseudomallei complex. A proposed novel species, B. humptydooensis sp. nov, was isolated from a bore water sample from the Northern Territory in Australia. B. humptydooensis sp. nov., is phylogenetically distinct from B. pseudomallei and other members of the pseudomallei complex making it the fifth member of this important group of bacteria.

Song Y.-M.,Sungkyunkwan University | Lee D.-H.,Seoul National University | Lee M.K.,Seoul National University | Lee K.,Inje University | And 5 more authors.
Twin Research and Human Genetics | Year: 2010

Determining valid zygosity is a basic and important requirement in a twin study, because misdiagnosing zygosity leads to biased results. The Healthy Twin Study has collected data from adult like-sex twins and their families since 2005. In the study, a questionnaire to determine zygosity was developed comprising four questions; one concerning the degree of resemblance, and three concerning the degree of confusion by the resemblance. Among 2,761 individuals (624 twin pairs) of twin and their families, 406 pairs of twins (mean age 38.3, 63.5% women) with both questionnaire and genotype information were selected to examine the validity of the zygosity questionnaire using 16 short tandem repeat markers. We first determined individual zygosity including undetermined category, and then decided the zygosity of a twin pair using a decision tree. Sensitivity of questionnaire diagnosis was 98.8% for monozygotic (MZ) and 88.9% for dizygotic (DZ) twins, and positive predictive value was 97.2% for MZ and 95.0% for DZ. When we compared correctly and wrongly diagnosed twin pairs, misdiagnosed DZ twins (nine pairs) showed striking similarity in stature or obesity even exceeding that of true MZ twins. Our finding suggests that a parsimonious questionnaire method of diagnosing the zygosity will be useful, and adding physical or physiological measurements to a questionnaire of zygosity diagnosis will either confound the correct diagnosis or reduce the efficiency of the study compared with using questionnaire alone or with introducing genotyping.

PubMed | Center for Genome science, University of Florida, U.S. National Cancer Institute, USAMRIID and 4 more.
Type: | Journal: BMC microbiology | Year: 2015

Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm) are Gram-negative facultative intracellular pathogens, which are the causative agents of melioidosis and glanders, respectively. Depending on the route of exposure, aerosol or transcutaneous, infection by Bp or Bm can result in an extensive range of disease - from acute to chronic, relapsing illness to fatal septicemia. Both diseases are associated with difficult diagnosis and high fatality rates. About ninety five percent of patients succumb to untreated septicemic infections and the fatality rate is 50 % even when standard antibiotic treatments are administered.The goal of this study is to profile murine macrophage-mediated phenotypic and molecular responses that are characteristic to a collection of Bp, Bm, Burkholderia thailandensis (Bt) and Burkholderia oklahomensis (Bo) strains obtained from humans, animals, environment and geographically diverse locations. Burkholderia spp. (N=21) were able to invade and replicate in macrophages, albeit to varying degrees. All Bp (N=9) and four Bm strains were able to induce actin polymerization on the bacterial surface following infection. Several Bp and Bm strains showed reduced ability to induce multinucleated giant cell (MNGC) formation, while Bo and Bp 776 were unable to induce this phenotype. Measurement of host cytokine responses revealed a statistically significant Bm mediated IL-6 and IL-10 production compared to Bp strains. Hierarchical clustering of transcriptional data from 84 mouse cytokines, chemokines and their corresponding receptors identified 29 host genes as indicators of differential responses between the Burkholderia spp. Further validation confirmed Bm mediated Il-1b, Il-10, Tnfrsf1b and Il-36a mRNA expressions were significantly higher when compared to Bp and Bt.These results characterize the phenotypic and immunological differences in the host innate response to pathogenic and avirulent Burkholderia strains and provide insight into the phenotypic alterations and molecular targets underlying host-Burkholderia interactions.

Olson M.A.,USAMRIID | Lee M.S.,USAMRIID | Lee M.S.,Center for Genome science | Lee M.S.,U.S. Army
Proteins: Structure, Function and Bioinformatics | Year: 2013

In this study, the application of temperature-based replica-exchange (T-ReX) simulations for structure refinement of decoys taken from the I-TASSER dataset was examined. A set of eight nonredundant proteins was investigated using self-guided Langevin dynamics (SGLD) with a generalized Born implicit solvent model to sample conformational space. For two of the protein test cases, a comparison of the SGLD/T-ReX method with that of a hybrid explicit/implicit solvent molecular dynamics T-ReX simulation model is provided. Additionally, the effect of side-chain placement among the starting decoy structures, using alternative rotamer conformations taken from the SCWRL4 modeling program, was investigated. The simulation results showed that, despite having near-native backbone conformations among the starting decoys, the determinant of their refinement is side-chain packing to a level that satisfies a minimum threshold of native contacts to allow efficient excursions toward the downhill refinement regime on the energy landscape. By repacking using SCWRL4 and by applying the RWplus statistical potential for structure identification, the SGLD/T-ReX simulations achieved refinement to an average of 38% increase in the number of native contacts relative to the original I-TASSER decoy sets and a 25% reduction in values of Cα root-mean-square deviation. The hybrid model succeeded in obtaining a sharper funnel to low-energy states for a modeled target than the implicit solvent SGLD model; yet, structure identification remained roughly the same. Without meeting a threshold of near-native packing of side chains, the T-ReX simulations degrade the accuracy of the decoys, and subsequently, refinement becomes tantamount to the protein folding problem. Proteins 2013. 2012 Published by Wiley Periodicals, Inc. Published 2012 Wiley Periodicals, Inc..

PubMed | U.S. Army, Center for Genome science and Los Alamos National Laboratory
Type: Journal Article | Journal: Genome announcements | Year: 2014

Burkholderia is a genus of betaproteobacteria that includes three notable human pathogens: B.cepacia, B.pseudomallei, and B.mallei. While B.pseudomallei and B.mallei are considered potential biowarfare agents, B.cepacia infections are largely limited to cystic fibrosis patients. Here, we present 56 Burkholderia genomes from 8 distinct species.

PubMed | U.S. Army, Center for Genome science and Los Alamos National Laboratory
Type: Journal Article | Journal: Genome announcements | Year: 2014

Listeria monocytogenes causes the food-borne illness listeriosis that primarily infects vulnerable groups (e.g., elderly adults, pregnant women, very young children, and the immunocompromised). We sequenced the genome of L.monocytogenes XXIII (ATCC 15313) and assembled it into a single scaffold (three contigs) and deposited the annotated assembly into GenBank as accession no. JOOX00000000.

Kim J.,Seoul National University | Oh S.,Seoul National University | Min H.,Center for Genome Science | Kim Y.,Center for Genome Science | Park T.,Seoul National University
Annals of the New York Academy of Sciences | Year: 2011

Genome-wide association studies (GWAS) have successfully identified many genetic variants that are associated with many complex traits. For example, GWAS can be useful for understanding the genetic basis of physical activity (PA). To date, however, there have been only a few GWAS regarding PA. In this article, we overview some practical issues for more efficient GWAS for PA: phenotype definition of PA, the analysis method, population stratification, replication, and sample size. We discuss these issues within a large-scale GWA data set from the Korea Association REsource (KARE) project, including 8,842 samples and 352,228 single nucleotide polymorphism (SNP) markers. Information on PA was obtained from questionnaires, and GWA analysis was performed to find genetic associations between PA and SNP markers in the Korean population. © 2011 New York Academy of Sciences..

PubMed | Center for Genome science, USAMRIID and Los Alamos National Laboratory
Type: Journal Article | Journal: Genome announcements | Year: 2014

Generally an opportunistic pathogen in the United States, Moraxella catarrhalis has acquired resistance to multiple antibacterial/antimicrobial agents. Here, we present the complete 1.9-Mb genome of M.catarrhalis strain ATCC 25240, as deposited in NCBI under the accession number CP008804.

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