22 research outputs found

    A new strategy for enhancing imputation quality of rare variants from next-generation sequencing data via combining SNP and exome chip data

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    Background: Rare variants have gathered increasing attention as a possible alternative source of missing heritability. Since next generation sequencing technology is not yet cost-effective for large-scale genomic studies, a widely used alternative approach is imputation. However, the imputation approach may be limited by the low accuracy of the imputed rare variants. To improve imputation accuracy of rare variants, various approaches have been suggested, including increasing the sample size of the reference panel, using sequencing data from study-specific samples (i.e., specific populations), and using local reference panels by genotyping or sequencing a subset of study samples. While these approaches mainly utilize reference panels, imputation accuracy of rare variants can also be increased by using exome chips containing rare variants. The exome chip contains 250 K rare variants selected from the discovered variants of about 12,000 sequenced samples. If exome chip data are available for previously genotyped samples, the combined approach using a genotype panel of merged data, including exome chips and SNP chips, should increase the imputation accuracy of rare variants. Results: In this study, we describe a combined imputation which uses both exome chip and SNP chip data simultaneously as a genotype panel. The effectiveness and performance of the combined approach was demonstrated using a reference panel of 848 samples constructed using exome sequencing data from the T2D-GENES consortium and 5,349 sample genotype panels consisting of an exome chip and SNP chip. As a result, the combined approach increased imputation quality up to 11 %, and genomic coverage for rare variants up to 117.7 % (MAF < 1 %), compared to imputation using the SNP chip alone. Also, we investigated the systematic effect of reference panels on imputation quality using five reference panels and three genotype panels. The best performing approach was the combination of the study specific reference panel and the genotype panel of combined data. Conclusions: Our study demonstrates that combined datasets, including SNP chips and exome chips, enhances both the imputation quality and genomic coverage of rare variants

    A Novel Small Molecule, 1,3-di-m-tolyl-urea, Inhibits and Disrupts Multispecies Oral Biofilms

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    An imbalance of homeostasis between the microbial communities and the host system leads to dysbiosis in oral micro flora. DMTU (1,3-di-m-tolyl-urea) is a biocompatible compound that was shown to inhibit Streptococcus mutans biofilm by inhibiting its communication system (quorum sensing). Here, we hypothesized that DMTU is able to inhibit multispecies biofilms. We developed a multispecies oral biofilm model, comprising an early colonizer Streptococcus gordonii, a bridge colonizer Fusobacterium nucleatum, and late colonizers Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. We performed comprehensive investigations to demonstrate the effect of DMTU on planktonic cells and biofilms. Our findings showed that DMTU inhibits and disrupts multispecies biofilms without bactericidal effects. Mechanistic studies revealed a significant down regulation of biofilm and virulence-related genes in P. gingivalis. Taken together, our study highlights the potential of DMTU to inhibit polymicrobial biofilm communities and their virulence

    A halogen bond-mediated highly active artificial chloride channel with high anticancer activity

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    10.1039/c8sc00602dChemical Science9174044-405

    Surface water and groundwater interactions in salt marshes and their impact on plant ecology and coastal biogeochemistry

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    Salt marshes are highly productive intertidal wetlands providing important ecological services for maintaining coastal biodiversity, buffering against oceanic storms, and acting as efficient carbon sinks. However, about half of these wetlands have been lost globally due to human activities and climate change. Inundated periodically by tidal water, salt marshes are subjected to strong surface water and groundwater interactions, which affect marsh plant growth and biogeochemical exchange with coastal water. This paper reviews the state of knowledge and current approaches to quantifying marsh surface water and groundwater interactions with a focus on porewater flow and associated soil conditions in connection with plant zonation as well as carbon, nitrogen, and greenhouse gas fluxes. Porewater flow and solute transport in salt marshes are primarily driven by tides with moderate regulation by rainfall, evapotranspiration and sea level rise. Tidal fluctuations play a key role in plant zonation through alteration of soil aeration and salt transport, and drive the export of significant fluxes of carbon and nutrients to coastal water. Despite recent progress, major knowledge gaps remain. Previous studies focused on flows in creek-perpendicular marsh sections and overlooked multi-scale 3D behaviors. Understanding of marsh ecological-hydrological links under combined influences of different forcing factors and boundary disturbances is lacking. Variations of surface water and groundwater temperatures affect porewater flow, soil conditions and biogeochemical exchanges, but the extent and underlying mechanisms remain unknown. We need to fill these knowledge gaps to advance understanding of salt marshes and thus enhance our ability to protect and restore them.ECO

    The Impact of the Oncotype DX Breast Cancer Assay on Treatment Decisions for Women With Estrogen Receptor-Positive, Node-Negative Breast Carcinoma in Hong Kong

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    © 2016 The Authors. Background: The Onco. type DX Breast Cancer Assay is validated to assess risk of distant recurrence and likelihood of chemotherapy (CT) benefit in estrogen receptor-positive ESBC in various populations. In Hong Kong, > 80% of breast cancers are early stage breast cancer (ESBC) and > 60% of these women receive CT. This prospective study measured changes in CT type and recommendations, as well as physician impression of assay impact in a homogenous Chinese population. Methods: Consecutive patients with estrogen receptor-positive, T1-3 N0-1mi M0 ESBC were offered enrollment. After surgery, physicians discussed treatment options with patients, then ordered the assay, then reassessed treatment recommendation considering assay results. Changes in treatment recommendation, CT utilization, physician confidence, and physician rating of influence on their treatment recommendations were measured. Results: A total of 146 evaluable patients received pre- and post-testing treatment recommendations. CT recommendations (including changes in intensity of CT) were changed for 34 of 146 patients (23.3%; 95% confidence interval, 16.7%-31.0%); change in intensity occurred in 7 of 146 (4.8%). There were 27 changes in treatment recommendations of adding or removing CT altogether (18.5% change; 95% confidence interval, 12.6%-25.8%). CT recommendations decreased from 52.1% to 37.7%, a net absolute reduction of 14.4% (P < .001; 27.6% net relative reduction). Pre-assay, 96% of physicians agreed/strongly agreed that they were confident in their treatment recommendation; post-assay, 90% of physicians agreed/strongly agreed with the same statement. Thirty percent of physicians agreed/strongly agreed that the test had influenced their recommendation, similar to the proportion of changed recommendations. Conclusions: The Onco. type DX Assay appears to influence physician ESBC adjuvant treatment recommendations in Hong Kong.Link_to_subscribed_fulltex
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