| 1. |
- Fang, Li Tai, et al.
(author)
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Establishing community reference samples, data and call sets for benchmarking cancer mutation detection using whole-genome sequencing
- 2021
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In: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 39:9, s. 1151-1160
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Journal article (peer-reviewed)abstract
- Tumor-normal paired DNA samples from a breast cancer cell line and a matched lymphoblastoid cell line enable calibration of clinical sequencing pipelines and benchmarking 'tumor-only' or 'matched tumor-normal' analyses. The lack of samples for generating standardized DNA datasets for setting up a sequencing pipeline or benchmarking the performance of different algorithms limits the implementation and uptake of cancer genomics. Here, we describe reference call sets obtained from paired tumor-normal genomic DNA (gDNA) samples derived from a breast cancer cell line-which is highly heterogeneous, with an aneuploid genome, and enriched in somatic alterations-and a matched lymphoblastoid cell line. We partially validated both somatic mutations and germline variants in these call sets via whole-exome sequencing (WES) with different sequencing platforms and targeted sequencing with >2,000-fold coverage, spanning 82% of genomic regions with high confidence. Although the gDNA reference samples are not representative of primary cancer cells from a clinical sample, when setting up a sequencing pipeline, they not only minimize potential biases from technologies, assays and informatics but also provide a unique resource for benchmarking 'tumor-only' or 'matched tumor-normal' analyses.
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| 2. |
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| 3. |
- Xiao, Wenming, et al.
(author)
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Toward best practice in cancer mutation detection with whole-genome and whole-exome sequencing
- 2021
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In: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 39:9, s. 1141-1150
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Journal article (peer-reviewed)abstract
- Recommendations are given on optimal read coverage and selection of calling algorithm to maximize the reproducibility of cancer mutation detection in whole-genome or whole-exome sequencing. Clinical applications of precision oncology require accurate tests that can distinguish true cancer-specific mutations from errors introduced at each step of next-generation sequencing (NGS). To date, no bulk sequencing study has addressed the effects of cross-site reproducibility, nor the biological, technical and computational factors that influence variant identification. Here we report a systematic interrogation of somatic mutations in paired tumor-normal cell lines to identify factors affecting detection reproducibility and accuracy at six different centers. Using whole-genome sequencing (WGS) and whole-exome sequencing (WES), we evaluated the reproducibility of different sample types with varying input amount and tumor purity, and multiple library construction protocols, followed by processing with nine bioinformatics pipelines. We found that read coverage and callers affected both WGS and WES reproducibility, but WES performance was influenced by insert fragment size, genomic copy content and the global imbalance score (GIV; G > T/C > A). Finally, taking into account library preparation protocol, tumor content, read coverage and bioinformatics processes concomitantly, we recommend actionable practices to improve the reproducibility and accuracy of NGS experiments for cancer mutation detection.
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| 4. |
- Anderson, Ryan T, et al.
(author)
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Association Between Seroclearance of Hepatitis B Surface Antigen and Long-term Clinical Outcomes of Patients With Chronic Hepatitis B Virus Infection : Systematic Review and Meta-analysis.
- 2021
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In: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 19:3, s. 463-472
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Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: Seroclearance of hepatitis B surface antigen (HBsAg) is the desired end point of treatment for chronic hepatitis B virus (HBV) infection, according to guidelines. We performed a systematic review and meta-analysis to evaluate the strength of the association between HBsAg seroclearance and long-term clinical outcomes.METHODS: We performed a systematic review of the PubMed, EMBASE, and Cochrane Library databases for articles that assessed HBsAg status and reported the incidence of hepatocellular carcinoma (HCC), liver decompensation, liver transplantation, and/or all-cause mortality during follow-up evaluation. We performed a meta-analysis of rate ratios (RR) using a random-effects model independently for each end point and for a composite end point.RESULTS: We analyzed data from 28 studies, comprising a total of 188,316 patients with chronic HBV infection (treated and untreated), and 1,486,081 person-years (PY) of follow-up evaluation; 26 reported data on HCC, 7 on liver decompensation, and 13 on liver transplantation and/or death. The composite event rates were 0.19/1000 PY for the HBsAg seroclearance group and 2.45/1000 PY for the HBsAg-persistent group. Pooled RRs for the HBsAg seroclearance group were 0.28 for liver decompensation (95% CI, 0.13-0.59; P = .001), 0.30 for HCC (95% CI, 0.20-0.44; P < .001), 0.22 for liver transplantation and/or death (95% CI, 0.13-0.39; P < .001), and 0.31 for the composite end point (95% CI, 0.23-0.43; P < .001). No differences in RR estimates were observed among subgroups of different study or patient characteristics.CONCLUSIONS: In a systematic review and meta-analysis, we found seroclearance of HBsAg to be associated significantly with improved patient outcomes. The results are consistent among different types of studies, in all patient subpopulations examined, and support the use of HBsAg seroclearance as a primary end point of trials of patients with chronic HBV infection.
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| 5. |
- Bräunig, Jennifer, et al.
(author)
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Fate and redistribution of perfluoroalkyl acids through AFFF-impacted groundwater
- 2017
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In: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 596, s. 360-368
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Journal article (peer-reviewed)abstract
- Leaching of perfluoroalkyl acids (PFAAs) from a local point source, a fire-fighting training area, has led to extensive contamination of a groundwater aquifer which has spread underneath part of a nearby town, Oakey, situated in the State of Queensland, Australia. Groundwater is extracted by residents from privately owned wells for daily activities such as watering livestock and garden beds. The concentration of 10 PFAAs in environmental and biological samples (water, soil, grass, chicken egg yolk, serum of horses, cattle and sheep), as well as human serum was investigated to determine the extent of contamination in the town and discuss fate and redistribution of PFAAs. Perfluorooctane sulfonate (PFOS) was the dominant PFAA in all matrices investigated, followed by perfluorohexane sulfonate (PFHxS). PFOS concentrations measured in water ranged between <0.17-14 mu g/L, concentrations of PFHxS measured between <0.07-6 mu g/L. PFAAs were detected in backyards (soil, grass), livestock and chicken egg yolk. Significant differences (p < 0.01) in PFOS and PFHxS concentrations in two groups of cattle were found, one held within the contamination plume, the other in the vicinity but outside of the contamination plume. In human serum PFOS concentrations ranged from 38 to 381 mu g/L, while PFHxS ranged from 39 to 214 mu g/L. Highest PFOS concentrations measured in human serum were >30-fold higher compared to the general Australian population. Through use of contaminated groundwater secondary sources of PFAA contamination are created on private property, leading to further redistribution of contamination and creation of additional human exposure pathways.
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| 6. |
- Dewapriya, Pradeep, et al.
(author)
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Novel Per- and Polyfluoroalkyl Substances Discovered in Cattle Exposed to AFFF-Impacted Groundwater
- 2023
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In: Environmental Science and Technology. - 0013-936X .- 1520-5851. ; 57:36, s. 13635-13645
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Journal article (peer-reviewed)abstract
- The leaching of per- and polyfluoroalkyl substances (PFASs) from Australian firefighting training grounds has resulted in extensive contamination of groundwater and nearby farmlands. Humans, farm animals, and wildlife in these areas may have been exposed to complex mixtures of PFASs from aqueous film-forming foams (AFFFs). This study aimed to identify PFAS classes in pooled whole blood (n = 4) and serum (n = 4) from cattle exposed to AFFF-impacted groundwater and potentially discover new PFASs in blood. Thirty PFASs were identified at various levels of confidence (levels 1a–5a), including three novel compounds: (i) perfluorohexanesulfonamido 2-hydroxypropanoic acid (FHxSA-HOPrA), (ii) methyl((perfluorohexyl)sulfonyl)sulfuramidous acid, and (iii) methyl((perfluorooctyl)sulfonyl)sulfuramidous acid, belonging to two different classes. Biotransformation intermediate, perfluorohexanesulfonamido propanoic acid (FHxSA-PrA), hitherto unreported in biological samples, was detected in both whole blood and serum. Furthermore, perfluoroalkyl sulfonamides, including perfluoropropane sulfonamide (FPrSA), perfluorobutane sulfonamide (FBSA), and perfluorohexane sulfonamide (FHxSA) were predominantly detected in whole blood, suggesting that these accumulate in the cell fraction of blood. The suspect screening revealed several fluoroalkyl chain-substituted PFAS. The results suggest that targeting only the major PFASs in the plasma or serum of AFFF-exposed mammals likely underestimates the toxicological risks associated with exposure. Future studies of AFFF-exposed populations should include whole-blood analysis with high-resolution mass spectrometry to understand the true extent of PFAS exposure.
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