| 1. |
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| 2. |
- Flannick, Jason, et al.
(författare)
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Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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| 3. |
- Fuchsberger, Christian, et al.
(författare)
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The genetic architecture of type 2 diabetes
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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| 4. |
- Manning, Alisa, et al.
(författare)
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A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
- 2017
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Ingår i: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
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| 5. |
- Christmas, Matthew, et al.
(författare)
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Evolutionary constraint and innovation across hundreds of placental mammals
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6643
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Tidskriftsartikel (refereegranskat)abstract
- Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (similar to 10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.
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| 6. |
- Murphy, Kathleen, 1972, et al.
(författare)
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Organic matter fluorescence in municipal water recycling schemes: Toward a unified PARAFAC model
- 2011
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Ingår i: Environmental Science & Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 45:7, s. 2909-2916
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Tidskriftsartikel (refereegranskat)abstract
- Organic matter (OM) is a ubiquitous constituent of natural waters quantifiable at very low levels using fluorescence spectroscopy. This technique has recognized potential in a range of applications where the ability to monitor water quality in real time is desirable, such as in water treatment systems. This study used PARAFAC to characterize a large (n = 1479) and diverse excitation emission matrix (EEM) data set from six recycled water treatment plants in Australia, for which sources of variability included geography, season, treatment processes, pH and fluorometer settings. Five components were identified independently in four or more plants, none of which were generated during the treatment process nor were typically entirely removed. PARAFAC scores could be obtained from EEMs by simple regression. The results have important implications for online monitoring of OM fluorescence in treatment plants, affecting choices regarding experimental design, instrumentation and the optimal wavelengths for tracking fluorescent organic matter through the treatment process. While the multimodel comparisons provide a compelling demonstration of PARAFAC's ability to distill chemical information from EEMs, deficiencies identified through this process have broad implications for interpreting and reusing (D)OM-PARAFAC models. © 2011 American Chemical Society.
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| 7. |
- Henderson, R.K., et al.
(författare)
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Evaluation of effluent organic matter fouling in ultrafiltration treatment using advanced organic characterisation techniques
- 2011
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Ingår i: Journal of Membrane Science. - : Elsevier BV. - 1873-3123 .- 0376-7388. ; 382:1-2, s. 50-59
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Tidskriftsartikel (refereegranskat)abstract
- Membrane fouling remains an operational challenge in the ultrafiltration (UF) membrane treatment of wastewater effluent and research is on-going to improve understanding of the organic character of foulants. Two advanced organic characterisation techniques that have potential to lend insight into membrane fouling are size exclusion chromatography with organic carbon, UV254 and nitrogen detection (LC-OCD) and fluorescence excitation-emission matrix (EEM) spectroscopy. In this study, UF treatment was undertaken for five tertiary wastewater effluents. The total hydraulic resistance was determined as well as that contributed by foulant layers fractionated by rinsing, backwashing and chemically desorbing. Organic characterisation for UF feed samples, permeates and each foulant layer was then performed using LC-OCD and FEEM spectroscopy with the aim of improving understanding of the character of foulants present in effluent organic matter (EfOM) and to determine the potential for the use of FEEM spectroscopy as a foulant indicator in such systems. It was determined that the biopolymer fraction was most significantly reduced on UF treatment, as anticipated due to its high molecular size. This was supported by the observation that the majority of the foulant layer comprised predominantly protein-enriched biopolymers (38-60% of total foulant layer DOC) that could be removed by rinsing. The resistance attributed to rinsing was directly related to the combined DOC concentration associated with proteins and low molecular weight neutral compounds as defined by LC-OCD analysis. Furthermore, tyrosine-like fluorescence intensity (λex/em=250/304nm) of both the rinsing solutions and UF feed samples showed good correlation with associated hydraulic resistance for EfOM originating from domestic wastewater, suggesting that fluorescence has potential to be used as a foulant indicator for these systems. © 2011 Elsevier B.V.
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| 8. |
- Cascone, Claudia, et al.
(författare)
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AbspectroscoPY, a Python toolbox for absorbance-based sensor data in water quality monitoring
- 2022
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Ingår i: Environmental Science: Water Research & Technology. - 2053-1419. ; 8:4, s. 836-848
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Tidskriftsartikel (refereegranskat)abstract
- The long-term trend of increasing natural organic matter (NOM) in boreal and north European surface waters represents an economic and environmental challenge for drinking water treatment plants (DWTPs). High-frequency measurements from absorbance-based online spectrophotometers are often used in modern DWTPs to measure the chromophoric fraction of dissolved organic matter (CDOM) over time. These data contain valuable information that can be used to optimise NOM removal at various stages of treatment and/or diagnose the causes of underperformance at the DWTP. However, automated monitoring systems generate large datasets that need careful preprocessing, followed by variable selection and signal processing before interpretation. In this work we introduce AbspectroscoPY (“Absorbance spectroscopic analysis inPython”), a Python toolbox for processing time-series datasets collected by in situ spectrophotometers. The toolbox addresses some of the main challenges in data preprocessing by handling duplicates, systematic time shifts, baseline corrections and outliers. It contains automated functions to compute a range of spectral metrics for the time-series data, including absorbance ratios, exponential fits, slope ratios and spectral slope curves. To demonstrate its utility, AbspectroscoPY was applied to 15-month datasets from three onlinespectrophotometers in a drinking water treatment plant. Despite only small variations in surface water quality over the time period, variability in the spectrophotometric profiles of treated water could be identified, quantified and related to lake turnover or operational changes in the DWTP. This toolboxrepresents a step toward automated early warning systems for detecting and responding to potential threats to treatment performance caused by rapid changes in incoming water quality.
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| 9. |
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| 10. |
- Murphy, Kathleen, 1972, et al.
(författare)
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Characterizing odorous emissions using new software for identifying peaks in chemometric models of gas chromatography-mass spectrometry datasets
- 2012
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Ingår i: Chemometrics and Intelligent Laboratory Systems. - : Elsevier BV. - 0169-7439 .- 1873-3239. ; 118, s. 41-50
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Tidskriftsartikel (refereegranskat)abstract
- The task of identifying individual compounds within complex gas chromatography - mass spectrometry (GC-MS) chromatograms is made more difficult by interferences between peaks with similar mass spectra eluting at the same time, typically against a background of chemical and electronic noise. Although chemometric techniques like parallel factor analysis and multivariate curve resolution can help to purify spectra and improve correlations with reference compounds, file incompatibilities between GC-MS acquisition software and modeling software prevent the modeled spectra from being easily compared to spectra in reference libraries. In this paper we present an enhancement to OpenChrom, an open-source software for chromatography and mass spectrometry, which implements the automated cross-matching of modeled spectra to NIST08 and NIST11 mass spectral databases. The benefits of this approach are demonstrated using a complex environmental dataset consisting of non-methane volatile organic compound emissions sampled on an Australian poultry farm. © 2012 Elsevier B.V.
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| 11. |
- Murphy, Kathleen, 1972, et al.
(författare)
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Exploring the limits of dissolved organic matter fluorescence for determining seawater sources and ballast water exchange on the US Pacific coast
- 2013
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Ingår i: Journal of Marine Systems. - : Elsevier BV. - 0924-7963. ; 111-112, s. 157-166
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Tidskriftsartikel (refereegranskat)abstract
- To minimize the risk of biological invasions associated with commercial shipping, vessels are required to conduct ballast water exchange (BWE)≤200 nautical miles offshore when arriving in the US from foreign ports, and some states require coastal BWE≤50 miles offshore along domestic routes. Previous research suggests that the intensity of fluorescent dissolved organic matter (fDOM) can be used to verify whether BWE was implemented. This study examined seasonal and spatial variability of fDOM in Pacific rim ports and the adjacent seas, using the North American coast as a model system to test whether regional fluorescence intensity thresholds consistently distinguish port sites from coastal and oceanic sites at increasing distances from shore. Over 2000 samples from major port systems on the US Pacific coast and along offshore (perpendicular) and alongshore (parallel) transects were analyzed. Overall, humic fDOM fluorescence intensity (C3*=370/494nm) effectively discriminated port versus oceanic sites located further than 100. miles from shore, but discriminated only a subset of coastal versus oceanic sources within the northeastern Pacific. Data from additional global ports are needed to predict the frequency of false positive or false negative ballast source determinations using fDOM for foreign vessel traffic. © 2012 Elsevier B.V.
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| 12. |
- Murphy, Kathleen, 1972, et al.
(författare)
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Fluorescence spectroscopy and multi-way techniques. PARAFAC
- 2013
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Ingår i: Analytical Methods. - : Royal Society of Chemistry (RSC). - 1759-9679 .- 1759-9660. ; 5:23, s. 6557-6566
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Tidskriftsartikel (refereegranskat)abstract
- PARAllel FACtor analysis (PARAFAC) is increasingly used to decompose fluorescence excitation emission matrices (EEMs) into their underlying chemical components. In the ideal case where fluorescence conforms to Beers Law, this process can lead to the mathematical identification and quantification of independently varying fluorophores. However, many practical and analytical hurdles stand between EEM datasets and their chemical interpretation. This article provides a tutorial in the practical application of PARAFAC to fluorescence datasets, demonstrated using a dissolved organic matter (DOM) fluorescence dataset. A new toolbox for MATLAB is presented to support improved visualisation and sensitivity analyses of PARAFAC models in fluorescence spectroscopy. © 2013 The Royal Society of Chemistry.
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| 13. |
- Murphy, Kathleen, 1972, et al.
(författare)
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Non-methane volatile organic compounds predict odor emitted from five tunnel ventilated broiler sheds
- 2014
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 95, s. 423-432
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Tidskriftsartikel (refereegranskat)abstract
- Non-methane volatile organic compounds (NMVOCs) emitted from mechanically ventilated poultry sheds in similar stages (32-36d) of broiler production were measured by thermal desorption-gas chromatography/mass spectrometry (TD-GC/MS), then identified using parallel factor analysis (PARAFAC2) and the NIST11 database. Calibration models predicting odor measured by dilution olfactometry from NMVOC concentrations via orthogonal projection to latent structures (O-PLS) made good predictions (Rp2=0.83-0.87, RMSEp=137-175OU) using one to eight NMVOCs with either one or two latent variables representing odor concentration and character, respectively. Similar changes in odorant composition were observed in each sampling campaign, with samples collected early in the day more odorous and more sulfurous than samples collected later in the day. High litter moisture favored sulfur-containing odorants over alcohols, aldehydes and ketones but had little bearing on perceived odor, whereas high bird density favored alcohols, aldehydes and ketones over sulfur-containing odorants. Eight VOCs that were important predictors of odor across all sheds in order of decreasing importance were dimethyl sulfide (DMS), dimethyl trisulfide (DMTS), 2-3 butanedione, 3-methyl-butanal, 1-butanol, 3-methyl-1-butanol, acetoin, and 2-butanone. Four additional NMVOCs also influenced perceived odor although less predictably; these were n-hexane, 2-butanol, dimethyl disulfide (DMDS), and 1-octen-3-ol. All of the odorants are associated with microbial or fungal activity in the litter and manure, except n-hexane, which may originate from hexane-extracted soybean meal in the chicken feed. The organosulfides measured in this study may have arisen from the field sites as well as from the degradation of thiols captured on sorbent tubes during analysis by TD-GC/MS. © 2013 Elsevier Ltd.
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| 14. |
- Murphy, Kathleen, 1972, et al.
(författare)
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OpenFluor- an online spectral library of auto-fluorescence by organic compounds in the environment
- 2014
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Ingår i: Analytical Methods. - : Royal Society of Chemistry (RSC). - 1759-9679 .- 1759-9660. ; 6:3, s. 658-661
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Tidskriftsartikel (refereegranskat)abstract
- An online repository of published organic fluorescence spectra has been developed, which can be searched for quantitative matches with any set of unknown spectra. It fills a critical gap by increasing access to measured and modelled (PARAFAC) spectra, and linking across studies and systems to reveal "global" fluorescence trends.
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| 15. |
- Paradina-Fernández, Lesly, et al.
(författare)
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Direct Measurement of Organic Micropollutants in Water and Wastewater Using Fluorescence Spectroscopy
- 2023
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Ingår i: ACS ES and T Water. - 2690-0637. ; 3:12, s. 3905-3915
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Tidskriftsartikel (refereegranskat)abstract
- Quantifying organic micropollutants (OMPs) in aquatic environments and assessing their removal by water treatment requires expensive and time-consuming analyses typically using liquid chromatographic separation and tandem mass spectrometry (LC-MS/MS). In this study, we evaluated the potential for detecting fluorescent OMPs via spectroscopy, which is cheap, rapid, and widely accessible. The method involved using a priori PARAFAC models to eliminate interfering background fluorescence emitted by naturally occurring dissolved organic matter. Of 20 screened pharmaceutical OMPs, three (ciprofloxacin, naproxen, and zolpidem) with calculated fluorescence quantum yields 0.14, 0.21, and 0.71, respectively, could be quantified in the low μg L-1 range when added alone or in combination to water samples without any sample pretreatment other than filtration and pH adjustment. Limits of detection for all three OMPs were 1.0-3.3 μg L-1 in surface waters, while in wastewater, they were 0.6-9.0 μg L-1 for ciprofloxacin and naproxen and 1.0-2.6 μg L-1 for zolpidem. Given the high cost of pharmaceutical analyses and widespread availability of fluorometers, the new approach will improve access to rapid and cost-effective results by supporting data-intensive lab-scale studies, wherein the types of OMPs studied and their concentration ranges are under the control of the analyst.
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