Prevalence and detection of low-allele-fraction variants in clinical cancer samples

Accurate detection of genomic alterations using high-throughput sequencing is an essential component of precision cancer medicine. We characterize the variant allele fractions (VAFs) of somatic single nucleotide variants and indels across 5095 clinical samples profiled using a custom panel, CancerSCAN. Our results demonstrate that a significant fraction of clinically actionable variants have low VAFs, often due to low tumor purity and treatment-induced mutations. The percentages of mutations under 5% VAF across hotspots in EGFR, KRAS, PIK3CA, and BRAF are 16%, 11%, 12%, and 10%, respectively, with 24% for EGFR T790M and 17% for PIK3CA E545. For clinical relevance, we describe two patients for whom targeted therapy achieved remission despite low VAF mutations. We also characterize the read depths necessary to achieve sensitivity and specificity comparable to current laboratory assays. These results show that capturing low VAF mutations at hotspots by sufficient sequencing coverage and carefully tuned algorithms is imperative for a clinical assay

Data from: Genome-wide association study for tobiano spotting coat color in Korean Jeju × Thoroughbred horse population

Korean Jeju horse features a small to medium frame size and stature having varieties of coat colors including grey, milky, spotted and bay1. Crossbreeding with Thoroughbred has been a long tradition in Korea to have intermediate frame size horse suitable for racing, leisure activities and meat production2. Tobiano white-spotting pattern is preferred by many horse breeders and owners which is inherited as an autosomal dominant trait1,3. Polymorphisms in proto-oncogene receptor tyrosine kinase (KIT) gene were strongly associated with tobiano and sabino coat color pattern in American and European horse breeds3,5. In addition, ECA3 inversion locus near KIT gene also significantly associated with tobiano spotting pattern in horses4,5. Here, we report SNPs and harbored genes associated with tobiano coat color in a crossbred horse population through genome-wide SNP association analysis. In this study, coat color patterns of 142 crossbred horses (Jeju indigenous horse × Thoroughbred) were verified according to previously described methods3,5 and coded as “0” or “1” (Figure S1). Genomic DNA was extracted from blood samples using DNeasy 96 blood DNA extraction Kit (QIAGEN, USA). Genotyping was performed using Equine SNP 50K BeadChip (Illumina, San Diego, USA) at AGBD, NIAS, Korea. A total of 45,204 SNPs passed the set quality control criteria as minor allele frequency (MAF0.10) and Hardy-Weinberg equilibrium (HWE<0.0001) in 142 individuals. Finally, a set of 16,223 independent SNPs were generated through –indep –pairwise 25 5 0.25 pruning6. Genome wide association study revealed 18 Bonferroni adjusted SNPs located on chromosome 3 (ECA3) significantly associated with tobiano coat color in the studied population (Figure 1, Table S1). These SNPs broadly plotted on 40 Mbp region (from 39 to 79 Mbp) of ECA3 which might be due to high LD among the significant SNPs. The most significant association was found between ECA3 inversion locus (77657979 bp) and tobiano pattern (P< 5.56×10-17) while the second highest association was detected with SNP rs68555258 (48853535 bp; P< 4.04×10-12, Table S1). Apart from this, genotypes of ECA3 inversion locus by pyrosequencing matched perfectly in our study (Table S2). All tobiano horses (n = 37) were heterozygous for inversion locus (+/To) while solid-colored horses (n = 103) were homozygous (+/+). ECA3 inversion is located 70 kbp downstream from KIT gene which possessed causal variants for tobiano pattern in horse5,6. The Biomart and Variant Effect Predictor tools in Ensembl Genome Browser (http://www.ensembl.org/index.html) identified several significant SNPs harboring genes of which GPRIN3, ARHGAP24, SCFD2, RASSL11B and WDFY3 are noticeable (Table S3). Based on our genome wide association and inversion locus genotyping results, it is suggested that ECA3 inversion locus variant is either causative or completely linked with causative variants for tobiano coat color in this crossbred horse population. Moreover, a set of putative mutations in other genes might be in high LD with causative variants that could be explored for functional annotations associated with tobiano coat color pattern in horse population

horse SNPs chip data

horse SNPs chip dat

A national discharge load of perfluoroalkyl acids derived from industrial wastewater treatment plants in Korea

Levels of 11 perfluoroalkyl acids (PFAAs), including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), were measured in wastewater (influent and effluent) and sludge samples collected from 25 industrial wastewater treatment plants (I-WWTPs) in five industrial sectors (chemicals, electronics, metals, paper, and textiles) in South Korea. The highest ???11PFAAs concentrations were detected in the influent and effluent from the paper (median: 411 ng/L) and textile (median: 106 ng/L) industries, and PFOA and PFOS were the predominant PFAAs (49-66%) in wastewater. Exceptionally high levels of PFAAs were detected in the sludge associated with the electronics (median: 91.0 ng/g) and chemical (median: 81.5 ng/g) industries with PFOS being the predominant PFAA. The discharge loads of 11 PFAAs from I-WWTP were calculated that total discharge loads for the five industries were 0.146 ton/yr. The textile industry had the highest discharge load with 0.055 ton/yr (PFOA: 0.039 ton/yr, PFOS: 0.010 ton/yr). Municipal wastewater contributed more to the overall discharge of PFAAs (0.489 ton/yr) due to the very small industrial wastewater discharge compared to municipal wastewater discharge, but the contribution of PFAAs from I-WWTPs cannot be ignored.clos

Updated national emission of perfluoroalkyl substances (PFASs) from wastewater treatment plants in South Korea

A nationwide emission estimate of perfluoroalkyl substances (PFASs) from wastewater treatment plants (WWTPs) is required to understand the source-receptor relationship of PFASs and to manage major types of WWTPs. In this study, the concentrations of 13 PFASs (8 perfluorocarboxylic acids, 3 perfluoroalkane sulfonates, and 2 intermediates) in wastewater and sludge from 81 WWTPs in South Korea were collected. The emission pathways of PFASs were redefined, and then the national emission of PFASs from WWTPs was rigorously updated. In addition to the direct calculations, Monte Carlo simulations were also used to calculate the likely range of PFAS emissions. The total (??13PFAS) emission (wastewater + sludge) calculated from the direct calculation with mean concentrations was 4.03 ton/y. The emissions of perfluorooctanoic acid (PFOA, 1.19 ton/y) and perfluorooctane sulfonate (PFOS, 1.01 ton/y) were dominant. The Monte Carlo simulations suggested that the realistic national emission of ??13PFASs is between 2 ton/y and 20 ton/y. Combined WWTPs treating municipal wastewater from residential and commercial areas were identified as a major emission source, contributing 65% to the total PFAS emissions. The Han and Nakdong Rivers were the primary contaminated rivers, receiving 89% of the total PFAS discharge from WWTPs. The results and methodologies in this study can be useful to establish a management policy for PFASs.close