Association Patterns of Ontological Features Signify Electronic Health Records in Liver Cancer

published_or_final_versio

Methylomic markers of persistent childhood asthma: a longitudinal study of asthma-discordant monozygotic twins.

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.Asthma is the most common chronic inflammatory disorder in children. The aetiology of asthma pathology is complex and highly heterogeneous, involving the interplay between genetic and environmental risk factors that is hypothesized to involve epigenetic processes. Our aim was to explore whether methylomic variation in early childhood is associated with discordance for asthma symptoms within monozygotic (MZ) twin pairs recruited from the Environmental Risk (E-Risk) longitudinal twin study. We also aimed to identify differences in DNA methylation that are associated with asthma that develops in childhood and persists into early adulthood as these may represent useful prognostic biomarkers. RESULTS: We examined genome-wide patterns of DNA methylation in buccal cell samples collected from 37 MZ twin pairs discordant for asthma at age 10. DNA methylation at individual CpG sites demonstrated significant variability within discordant MZ twin pairs with the top-ranked nominally significant differentially methylated position (DMP) located in the HGSNAT gene. We stratified our analysis by assessing DNA methylation differences in a sub-group of MZ twin pairs who remained persistently discordant for asthma at age 18. The top-ranked nominally significant DMP associated with persisting asthma is located in the vicinity of the HLX gene, which has been previously implicated in childhood asthma. CONCLUSIONS: We identified DNA methylation differences associated with childhood asthma in peripheral DNA samples from discordant MZ twin pairs. Our data suggest that differences in DNA methylation associated with childhood asthma which persists into early adulthood are distinct from those associated with asthma which remits.Medical Research Council (MRC)National Institute of Child Health and Development (NICHD)American Asthma FoundationMRC Centenary Awar

Is sex lost in translation? Linguistic and conceptual issues in the translation of sexual and reproductive health surveys

Translated questionnaires are increasingly used in population health research. Nevertheless, translation is often not conducted with the same rigour as the process of survey development in the original language. This has serious limitations and may introduce bias in question relevance and meaning. This article describes and reflects on the process of translating a large and complex sexual and reproductive health survey from English into Simplified Chinese. We interrogated assumptions embedded in taken-for-granted translation practice to locate the sociocultural origins of these assumptions. We discuss how terminology and expression related to sexual and reproductive health may lose their conceptual or linguistic significance during translation in three different ways. Firstly, meanings can be lost in the negotiation of meanings associated with linguacultural and geographical variations of terminology. Secondly, meanings can be lost in the clash between everyday and professional sexual and reproductive health discourses. Thirdly, meanings can be lost due to the design of the source questionnaire and the intended mode of survey administration. We discuss ways to help overcome the unavoidable translation challenges that arise in the process of translating English sexual and reproductive health surveys for migrants from non-English speaking backgrounds

Unsupervised fuzzy pattern discovery in gene expression data

2010-2011 > Academic research: refereed > Publication in refereed journalpublished_fina

Identification of microRNA 885-5p as a novel regulator of tumor metastasis by targeting CPEB2 in colorectal cancer

published_or_final_versio

The clinicopathological significance of miR-133a in colorectal cancer

This study determined the expression of microRNA-133a (MiR-133a) in colorectal cancer (CRC) and adjacent normal mucosa samples and evaluated its clinicopathological role in CRC. The expression of miR-133a in 125 pairs of tissue samples was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and correlated with patient's clinicopathological data by statistical analysis. Endogenous expression levels of several potential target genes were determined by qRT-PCR and correlated using Pearson's method. MiR-133a was downregulated in 83.2% of tumors compared to normal mucosal tissue. Higher miR-133a expression in tumor tissues was associated with development of distant metastasis, advanced Dukes and TNM staging, and poor survival. The unfavorable prognosis of higher miR-133a expression was accompanied by dysregulation of potential miR-133a target genes, LIM and SH3 domain protein 1 (LASP1), Caveolin-1 (CAV1), and Fascin-1 (FSCN1). LASP1 was found to possess a negative correlation (γ=-0.23), whereas CAV1 exhibited a significant positive correlation (γ=0.27), and a stronger correlation was found in patients who developed distant metastases (γ=0.42). In addition, a negative correlation of FSCN1 was only found in nonmetastatic patients. In conclusion, miR-133a was downregulated in CRC tissues, but its higher expression correlated with adverse clinical characteristics and poor prognosis. © 2014 Timothy Ming-Hun Wan et al.published_or_final_versio

Prognostication of serial post-intensity-modulated radiation therapy undetectable plasma EBV DNA for nasopharyngeal carcinoma

published_or_final_versio

Gene-Based Meta-Analysis of Genome-Wide Association Study Data Identifies Independent Single-Nucleotide Polymorphisms in ANXA6 as Being Associated With Systemic Lupus Erythematosus in Asian Populations

Objective Previous genome-wide association studies (GWAS), which were mainly based on single-variant analysis, have identified many systemic lupus erythematosus (SLE) susceptibility loci. However, the genetic architecture of this complex disease is far from being understood. The aim of this study was to investigate whether using a gene-based analysis may help to identify novel loci, by considering global evidence of association from a gene or a genomic region rather than focusing on evidence for individual variants. Methods Based on the results of a meta-analysis of 2 GWAS of SLE conducted in 2 Asian cohorts, we performed an in-depth gene-based analysis followed by replication in a total of 4,626 patients and 7,466 control subjects of Asian ancestry. Differential allelic expression was measured by pyrosequencing. Results More than one-half of the reported SLE susceptibility loci showed evidence of independent effects, and this finding is important for understanding the mechanisms of association and explaining disease heritability. ANXA6 was detected as a novel SLE susceptibility gene, with several single-nucleotide polymorphisms (SNPs) contributing independently to the association with disease. The risk allele of rs11960458 correlated significantly with increased expression of ANXA6 in peripheral blood mononuclear cells from heterozygous healthy control subjects. Several other associated SNPs may also regulate ANXA6 expression, according to data obtained from public databases. Higher expression of ANXA6 in patients with SLE was also reported previously. Conclusion Our study demonstrated the merit of using gene-based analysis to identify novel susceptibility loci, especially those with independent effects, and also demonstrated the widespread presence of loci with independent effects in SLE susceptibility genes. © 2015, American College of Rheumatology.postprin