| 1. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 2. |
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| 3. |
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| 5. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 6. |
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| 7. |
- Romagnoni, A, et al.
(författare)
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Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10351-
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Tidskriftsartikel (refereegranskat)abstract
- Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers.
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| 8. |
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| 9. |
- Nagaraja, Ch., et al.
(författare)
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Opening remarks
- 2016
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Konferensbidrag (refereegranskat)
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| 10. |
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| 11. |
- Momozawa, Y, et al.
(författare)
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IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2427-
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Tidskriftsartikel (refereegranskat)abstract
- GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach.
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| 12. |
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| 13. |
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| 14. |
- Blösch, Günter, et al.
(författare)
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Twenty-three unsolved problems in hydrology (UPH) - a community perspective
- 2019
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Ingår i: Hydrological Sciences Journal. - : Informa UK Limited. - 0262-6667 .- 2150-3435. ; 64:10, s. 1141-1158
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Tidskriftsartikel (refereegranskat)abstract
- This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure involved a public consultation through online media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focused on the process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come.
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| 15. |
- Hou, T. P., et al.
(författare)
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Magnetic-field-induced magnetism and thermal stability of carbides Fe6-xMoxC in molybdenum-containing steels
- 2016
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Ingår i: Acta Materialia. - : Elsevier. - 1359-6454 .- 1873-2453. ; 102, s. 24-31
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Tidskriftsartikel (refereegranskat)abstract
- A hybrid method combining first-principles calculations and Weiss molecular field theory with thermodynamic data has been implemented to explore the origin of magnetic-field-induced precipitation behaviors for alloy carbides. The paramagnetic Mo atom disturbed the order of magnetic moment and resulted in a decrease in the Curie temperature for alloy carbide Fe6-xMoxC. The temperature dependence of magnetic moment and saturation magnetization of Fe atoms at different Wyckoff positions, as well as the saturation or induced magnetization of Fe6-xMoxC, decreased with increasing temperature. The higher Fe content and external magnetic field greatly increased the magnetization of alloy carbides. Two kinds of stella quadrangula lattices were employed to account for the total magnetism which was derived from the contribution of different Wyckoff sites of Fe atoms and Fe-C distances. The calculated total free energy taking into account magnetic field, temperature and composition was sufficient to provide quantitative agreement with experiment. The investigation of the effects of external field on the carbide precipitation behaviors led to a better understanding of the magnetic-field-induced phase transformation mechanism in heat resistant steels.
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| 16. |
- Hou, T. P., et al.
(författare)
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The determining role of magnetic field in iron and alloy carbide precipitation behaviors under the external field
- 2016
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Ingår i: Scripta Materialia. - : Elsevier. - 1359-6462 .- 1872-8456. ; 120, s. 76-79
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Tidskriftsartikel (refereegranskat)abstract
- A combined approach to calculate the thermodynamic properties of iron and alloy carbides including the thermal and magnetic contribution is derived. Special emphasis is placed on the role of Fe and Mo to the Gibbs free energy. Lower Mo concentration in the carbides corresponds to a higher thermal Gibbs free energy change. The higher Fe content and external magnetic field greatly increase the induced magnetization, reducing the magnetic Gibbs free energy substantially and therefore increase the formation temperature. The stability of M 2 C and M 3 C are mainly determined by the thermal factors, whereas magnetic field has a predominant contribution for M 6 C.
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| 17. |
- Jessop-Fabre, Mathew M., et al.
(författare)
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EasyClone-MarkerFree: A vector toolkit for marker-less integration of genes into Saccharomyces cerevisiae via CRISPR-Cas9
- 2016
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Ingår i: Biotechnology journal. - : Wiley. - 1860-6768 .- 1860-7314. ; 11:8, s. 1110-1117
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Tidskriftsartikel (refereegranskat)abstract
- Saccharomyces cerevisiae is an established industrial host for production of recombinant proteins, fuels and chemicals. To enable stable integration of multiple marker-free overexpression cassettes in the genome of S. cerevisiae, we have developed a vector toolkit EasyClone-MarkerFree. The integration of linearized expression cassettes into defined genomic loci is facilitated by CRISPR/Cas9. Cas9 is recruited to the chromosomal location by specific guide RNAs (gRNAs) expressed from a set of gRNA helper vectors. Using our genome engineering vector suite, single and triple insertions are obtained with 90–100% and 60–70% targeting efficiency, respectively. We demonstrate application of the vector toolkit by constructing a haploid laboratory strain (CEN.PK113-7D) and a diploid industrial strain (Ethanol Red) for production of 3-hydroxypropionic acid, where we tested three different acetyl-CoA supply strategies, requiring overexpression of three to six genes each. Among the tested strategies was a bacterial cytosolic pyruvate dehydrogenase complex, which was integrated into the genome in a single transformation. The publicly available EasyClone-MarkerFree vector suite allows for facile and highly standardized genome engineering, and should be of particular interest to researchers working on yeast chassis with limited markers available.
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| 18. |
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| 19. |
- O’Reilly, Catherine M., et al.
(författare)
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Rapid and highly variable warming of lake surface waters around the globe
- 2015
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 42:24
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Tidskriftsartikel (refereegranskat)abstract
- In this first worldwide synthesis of in situ and satellite-derived lake data, we find that lake summer surface water temperatures rose rapidly (global mean = 0.34°C decade−1) between 1985 and 2009. Our analyses show that surface water warming rates are dependent on combinations of climate and local characteristics, rather than just lake location, leading to the counterintuitive result that regional consistency in lake warming is the exception, rather than the rule. The most rapidly warming lakes are widely geographically distributed, and their warming is associated with interactions among different climatic factors—from seasonally ice-covered lakes in areas where temperature and solar radiation are increasing while cloud cover is diminishing (0.72°C decade−1) to ice-free lakes experiencing increases in air temperature and solar radiation (0.53°C decade−1). The pervasive and rapid warming observed here signals the urgent need to incorporate climate impacts into vulnerability assessments and adaptation efforts for lakes.
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| 20. |
- Rainsley, Eleanor, et al.
(författare)
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Pleistocene glacial history of the New Zealand subantarctic islands
- 2019
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 15:2, s. 423-448
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Tidskriftsartikel (refereegranskat)abstract
- The New Zealand subantarctic islands of Auckland and Campbell, situated between the subtropical front and the Antarctic Convergence in the Pacific sector of the Southern Ocean, provide valuable terrestrial records from a globally important climatic region. Whilst the islands show clear evidence of past glaciation, the timing and mechanisms behind Pleistocene environmental and climate changes remain uncertain. Here we present a multidisciplinary study of the islands-including marine and terrestrial geomorphological surveys, extensive analyses of sedimentary sequences, a comprehensive dating programme, and glacier flow line modelling-to investigate multiple phases of glaciation across the islands. We find evidence that the Auckland Islands hosted a small ice cap 384 000 +/- 26 000 years ago (384 +/- 26 ka), most likely during Marine Isotope Stage 10, a period when the subtropical front was reportedly north of its present-day latitude by several degrees, and consistent with hemispheric-wide glacial expansion. Flow line modelling constrained by field evidence suggests a more restricted glacial period prior to the LGM that formed substantial valley glaciers on the Campbell and Auckland Islands around 72-62 ka. Despite previous interpretations that suggest the maximum glacial extent occurred in the form of valley glaciation at the Last Glacial Maximum (LGM; similar to 21 ka), our combined approach suggests minimal LGM glaciation across the New Zealand subantarctic islands and that no glaciers were present during the Antarctic Cold Reversal (ACR; similar to 15-13 ka). Instead, modelling implies that despite a regional mean annual air temperature depression of similar to 5 degrees C during the LGM, a combination of high seasonality and low precipitation left the islands incapable of sustaining significant glaciation. We suggest that northwards expansion of winter sea ice during the LGM and subsequent ACR led to precipitation starvation across the middle to high latitudes of the Southern Ocean, resulting in restricted glaciation of the subantarctic islands.
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| 21. |
- Zhao, Chaoyang, et al.
(författare)
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A massive expansion of effector genes underlies gall-formation in the wheat pest Mayetiola destructor
- 2015
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Ingår i: Current Biology. - : Elsevier BV. - 1879-0445 .- 0960-9822. ; 25:5, s. 613-620
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Tidskriftsartikel (refereegranskat)abstract
- Gall-forming arthropods are highly specialized herbivores that, in combination with their hosts, produce extended phenotypes with unique morphologies [1]. Many are economically important, and others have improved our understanding of ecology and adaptive radiation [2]. However, the mechanisms that these arthropods use to induce plant galls are poorly understood. We sequenced the genome of the Hessian fly (Mayetiola destructor; Diptera: Cecidomyiidae), a plant parasitic gall midge and a pest of wheat (Triticum spp.), with the aim of identifying genic modifications that contribute to its plant-parasitic lifestyle. Among several adaptive modifications, we discovered an expansive reservoir of potential effector proteins. Nearly 5% of the 20,163 predicted gene models matched putative effector gene transcripts present in the M. destructor larval salivary gland. Another 466 putative effectors were discovered among the genes that have no sequence similarities in other organisms. The largest known arthropod gene family (family SSGP-71) was also discovered within the effector reservoir. SSGP-71 proteins lack sequence homologies to other proteins, but their structures resemble both ubiquitin E3 ligases in plants and E3-ligase-mimicking effectors in plant pathogenic bacteria. SSGP-71 proteins and wheat Skp proteins interact in vivo. Mutations in different SSGP-71 genes avoid the effector-triggered immunity that is directed by the wheat resistance genes H6 and H9. Results point to effectors as the agents responsible for arthropod-induced plant gall formation.
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