The human reference genome, maintained by the Genome Reference Consortium, is conceivably the most complete genome assembly ever, since its first construction. It has continually been improved by ...incorporating corrections made to the previous assemblies, thanks to various technological advances. Many currently-ongoing population sequencing projects have been based on this reference genome, heightening hopes of the development of useful medical applications of genomic information, thanks to the recent maturation of high-throughput sequencing technologies. However, just one reference genome does not fit all the populations across the globe, because of the large diversity in genomic structures and technical limitations inherent to short read sequencing methods. The recent success in de novo construction of the highly contiguous Asian diploid genome AK1, by combining single molecule technologies with routine sequencing data without resorting to traditional clone-by-clone sequencing and physical mapping, reveals the nature of genomic structure variation by detecting thousands of novel structural variations and by finally filling in some of the prior gaps which had persistently remained in the current human reference genome. Now it is expected that the AK1 genome, soon to be paired with more upcoming de novo assembled genomes, will provide a chance to explore what it is really like to use ancestry-specific reference genomes instead of hg19/hg38 for population genomics. This is a major step towards the furthering of genetically-based precision medicine. BMB Reports 2016; 49(12): 653-654
Our goal was to examine the effect of area-level deprivation on patient survival time for seven major cancers - stomach, colon, liver, lung, breast, cervix, and thyroid cancer. Data on 10,902 ...subjects who were diagnosed with major cancers from 2010 and 2011 in Busan were collected regarding the survival time along with several important prognostic factors and an area-level deprivation index was constructed from education, income, unemployment, and welfare assistance, to assess the comprehensive area-level socioeconomic status. A multilevel Cox proportional hazard model was used to investigate the effects of multiple risk factors such as gender, age, tumor stage, diagnosis path, and the area-level deprivation. After adjusting for risk factors the area-level deprivation index was found to be significant in associating with higher hazard rate for several cancers. Estimated hazard ratios (95% CI) were 1.08 (0.99-1.18), 1.23 (1.12-1.36), 1.36 (1.21-1.53) for the second, the third, and the fourth quartile of deprivation index groups, respectively, when compared to the least deprived group. When compared with the least deprived group, the more deprived group showed significant decrease in survival time for major cancers. This novel finding may contribute to the literature regarding the association of area-level socioeconomic status and highlight the importance of careful monitoring of socioeconomic characteristics for cancer prevention and care services.
Tea is the world＇s oldest and most popular caffeine-containing beverage with immense economic, medicinal, and cultural importance. Here, we present the first high-quality nucleotide sequence of the ...repeat-rich （80.9%）, 3.02-Gb genome of the cultivated tea tree Camellia sinensis. We show that an extraordinarily large genome size of tea tree is resulted from the slow, steady, and long-term amplification of a few LTR retrotransposon families. In addition to a recent whole-genome duplication event, lineage-specific expansions of genes associated with flavonoid metabolic biosynthesis were discovered, which enhance catechin production, terpene enzyme activation, and stress tolerance, important features for tea flavor and adaptation. We demonstrate an independent and rapid evolution of the tea caffeine synthesis pathway relative to cacao and coffee. A comparative study among 25 Camellia species revealed that higher expression levels of most flavonoid- and caffeinebut not theanine-related genes contribute to the increased production of catechins and caffeine and thus enhance tea-processing suitability and tea quality. These novel findings pave the way for further metabolomic and functional genomic refinement of characteristic biosynthesis pathways and will help develop a more diversified set of tea flavors that would eventually satisfy and attract more tea drinkers worldwide.
The prevalence of multiple chronic conditions (MCC), defined as several coexisting chronic conditions, has increased with the aging of society. MCC is associated with poor outcomes, but most comorbid ...diseases in asthma patients have been evaluated as asthma-associated diseases. We investigated the morbidity of coexisting chronic diseases in asthma patients and their medical burdens.
We analyzed data from the National Health Insurance Service-National Sample Cohort for 2002-2013. We defined MCC with asthma as a group of one or more chronic diseases in addition to asthma. We analyzed 20 chronic conditions, including asthma. Age was categorized into groups 1-5 (< 10, 10-29, 30-44, 45-64, and ≥ 65 years, respectively). The frequency of medical system use and associated costs were analyzed to determine the asthma-related medical burden in patients with MCC.
The prevalence of asthma was 13.01%, and the prevalence of MCC in asthmatic patients was 36.55%. The prevalence of MCC with asthma was higher in females than males and increased with age. The significant comorbidities were hypertension, dyslipidemia, arthritis, and diabetes. Dyslipidemia, arthritis, depression, and osteoporosis were more common in females than males. Hypertension, diabetes, COPD, coronary artery disease, cancer, and hepatitis were more prevalent in males than females. According to age, the most prevalent chronic condition in groups 1 and 2 was depression, dyslipidemia in group 3, and hypertension in groups 4 and 5. Older age, low income, and severe disability were independent risk factors for MCC in patients with asthma. The frequency of asthma-related medical system use and asthma-associated costs increased with increasing numbers of coexisting chronic diseases.
Comorbid chronic diseases in asthma patients differed according to age and sex. The asthma-related-medical burdens were highest in patients with five or more chronic conditions and groups 1 and 5.
To examine the effect of individual and area-level characteristics on the probability of public-private mix (PPM) support (PPM coverage) for tuberculosis (TB).
This study is a retrospective cohort ...design using TB reporting and treatment management data in Korea. We analyzed PPM coverage through multilevel logistic regression and empirical Bayesian estimation according to individual and area-level characteristics and their interaction.
Patients aged 0-29 years, women, of Korean nationality, treated at a general hospital, a one-time reporting, urban areas, and the lowest deprivation index (DI) showed higher PPM coverage. Due to the cross-level interaction, PPM coverage in the urban areas (slope=-0.048, p<0.001) had a higher level but a steeper negative deprivation gradient than in rural areas (slope= -0.015, p<0.001). For a general hospital, the PPM coverage in urban is high but more significantly decreased than in rural areas with the higher DI (urban: slope=-0.047, p<0.001; rural: slope=-0.031, p<0.001). For clinics and hospitals, the effect of DI did not appear in urban areas, but in rural areas, the higher the DI, the higher the PPM coverage with a slope of 0.046 (p<0.001) and 0.063 (p<0.001), respectively.
The PPM program created a significant disparity in PPM coverage between urban-rural areas and type of healthcare provider according to DI. Considering the high risk of TB incidence in areas with higher DI, institutional improvement and program redesign are needed to improve accessibility and equity.
Whole genome bisulfite sequencing (WGBS), with its ability to interrogate methylation status at single CpG site resolution epigenome-wide, is a powerful technique for use in molecular experiments. ...Here, we aim to advance strategies for accurate and efficient WGBS for application in future large-scale epidemiological studies. We systematically compared the performance of three WGBS library preparation methods with low DNA input requirement (Swift Biosciences Accel-NGS, Illumina TruSeq and QIAGEN QIAseq) on two state-of-the-art sequencing platforms (Illumina NovaSeq and HiSeq X), and also assessed concordance between data generated by WGBS and methylation arrays. Swift achieved the highest proportion of CpG sites assayed and effective coverage at 26x (P < 0.001). TruSeq suffered from the highest proportion of PCR duplicates, while QIAseq failed to deliver across all quality metrics. There was little difference in performance between NovaSeq and HiSeq X, with the exception of higher read duplication rate on the NovaSeq (P < 0.05), likely attributable to the higher cluster densities on its flow cells. Systematic biases exist between WGBS and methylation arrays, with lower precision observed for WGBS across the range of depths investigated. To achieve a level of precision broadly comparable to the methylation array, a minimum coverage of 100x is recommended.
This study investigated the treatment outcomes, and factors affecting the outcomes, of new tuberculosis (TB) patients in Busan, South Korea.
We retrospectively analysed the citywide TB registry data ...(collected for the Korean National TB Surveillance System) of new TB patients registered in Busan from January 2014 to December 2015.
A total of 4732 patients were included in this study (mean age, 52.5 ± 19.9 years; 58.4% male). The overall treatment success rate was 83.9% (cured, 20.2%; completed, 63.7%); 8.0% of patients died, and 3.6% were lost to follow-up. In multivariate analyses, a higher rate of loss to follow-up was associated with foreign nationality, registered as TB-positive at least twice, and being in Q4 (fourth quintile) or Q5 (fifth quintile) of the regional deprivation index. Conversely, a lower rate of loss to follow-up was associated with female gender, smear-positive for pulmonary TB (PTB), and the treatment outcome being reported by a public health centre. Higher mortality was associated with old age (≥ 75 years), smear-positive PTB, treatment outcome being reported by the hospital, and being registered as TB-positive twice. Lower mortality was associated with female gender, treatment outcome being reported by a public health centre or clinic, and Q5 of the regional deprivation index.
Treatment outcomes of new TB patients were sub-optimal in Busan. TB control programs should maintain close monitoring and provide greater socioeconomic support to patients at high risk of poor treatment outcomes.
Flammulina velutipes is a fungus with health and medicinal benefits that has been used for consumption and cultivation in East Asia. F. velutipes is also known to degrade lignocellulose and produce ...ethanol. The overlapping interests of mushroom production and wood bioconversion make F. velutipes an attractive new model for fungal wood related studies. Here, we present the complete sequence of the F. velutipes genome. This is the first sequenced genome for a commercially produced edible mushroom that also degrades wood. The 35.6-Mb genome contained 12,218 predicted protein-encoding genes and 287 tRNA genes assembled into 11 scaffolds corresponding with the 11 chromosomes of strain KACC42780. The 88.4-kb mitochondrial genome contained 35 genes. Well-developed wood degrading machinery with strong potential for lignin degradation (69 auxiliary activities, formerly FOLymes) and carbohydrate degradation (392 CAZymes), along with 58 alcohol dehydrogenase genes were highly expressed in the mycelium, demonstrating the potential application of this organism to bioethanol production. Thus, the newly uncovered wood degrading capacity and sequential nature of this process in F. velutipes, offer interesting possibilities for more detailed studies on either lignin or (hemi-) cellulose degradation in complex wood substrates. The mutual interest in wood degradation by the mushroom industry and (ligno-)cellulose biomass related industries further increase the significance of F. velutipes as a new model.
The accurate identification of genetic variants contributing to therapeutic drug response or adverse effects is the first step in implementation of precision drug therapy. Targeted sequencing has ...recently become a common methodology for large-scale studies of genetic variation thanks to its favorable balance between low cost, high throughput, and deep coverage. Here, we present ClinPharmSeq, a targeted sequencing panel of 59 genes with associations to pharmacogenetic (PGx) phenotypes, as a platform to explore the relationship between drug response and genetic variation, both common and rare. For validation, we sequenced DNA from 64 ethnically diverse Coriell samples with ClinPharmSeq to call star alleles (haplotype patterns) in 27 genes using the bioinformatics tool PyPGx. These reference samples were extensively characterized by multiple laboratories using PGx testing assays and, more recently, whole genome sequencing. We found that ClinPharmSeq can consistently generate deep-coverage data (mean = 274x) with high uniformity (30x or above = 94.8%). Our genotype analysis identified a total of 185 unique star alleles from sequencing data, and showed that diplotype calls from ClinPharmSeq are highly concordant with that from previous publications (97.6%) and whole genome sequencing (97.9%). Notably, all 19 star alleles with complex structural variation including gene deletions, duplications, and hybrids were recalled with 100% accuracy. Altogether, these results demonstrate that the ClinPharmSeq platform offers a feasible path for broad implementation of PGx testing and optimization of individual drug treatments.
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