| 1. |
- Sodergren, Erica, et al.
(författare)
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The genome of the sea urchin Strongylocentrotus purpuratus.
- 2006
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
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Tidskriftsartikel (refereegranskat)abstract
- We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
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| 2. |
- Law, Philip J., et al.
(författare)
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Association analyses identify 31 new risk loci for colorectal cancer susceptibility
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.
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| 3. |
- Patterson, Nick, et al.
(författare)
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Large-scale migration into Britain during the Middle to Late Bronze Age
- 2022
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594
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Tidskriftsartikel (refereegranskat)abstract
- Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
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| 4. |
- Al Jebali, Ramsey, et al.
(författare)
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A helium gas scintillator active target for photoreaction measurements
- 2015
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Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001. ; 51:10
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Tidskriftsartikel (refereegranskat)abstract
- A multi-cell He gas scintillator active target, designed for the measurement of photoreaction cross sections, is described. The target has four main chambers, giving an overall thickness of 0.103 g/cm(3) at an operating pressure of 2MPa. Scintillations are read out by photomultiplier tubes and the addition of small amounts of N-2 to the He, to shift the scintillation emission from UV to visible, is discussed. First results of measurements at the MAX IV Laboratory tagged-photon facility show that the target has a timing resolution of around 1 ns and can cope well with a high-flux photon beam. The determination of reaction cross sections from target yields relies on a Monte Carlo simulation, which considers scintillation light transport, photodisintegration processes in He-4, background photon interactions in target windows and interactions of the reaction-product particles in the gas and target container. The predictions of this simulation are compared to the measured target response.
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| 5. |
- Aryani, Amir, et al.
(författare)
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Change propagation analysis using domain information
- 2009
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Ingår i: Proceedings of the Australian Software Engineering Conference, ASWEC. - 9780769535999 ; , s. 34-43
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Konferensbidrag (refereegranskat)abstract
- We propose a novel methodology for analysing change propagation in software using the domain-level behavioural model of a system. We hypothesize that change propagation analysis is feasible based purely on the information visible and understandable to domain experts, trading some accuracy for productivity. Such a method is independent of formal architectural representations and may be practical for applications with heterogeneous subsystems, or missing or undocumented source code. In this paper we introduce the first phase of the methodology: creating and evaluating a connection graph of conceptual relationships between user interface components. We provide results of case studies on two web-based systems which illustrate how our methodology can be applied, and how discovered conceptual relationships match the architectural dependencies.
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| 6. |
- Belov, Vladimir, et al.
(författare)
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Multi-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures
- 2024
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Ingår i: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may yield more encouraging prospects.
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| 7. |
- Bonner, Stephen, et al.
(författare)
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A review of biomedical datasets relating to drug discovery: a knowledge graph perspective
- 2022
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Ingår i: Briefings in Bioinformatics. - : Oxford University Press (OUP). - 1467-5463 .- 1477-4054. ; In Press
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Forskningsöversikt (refereegranskat)abstract
- Drug discovery and development is a complex and costly process. Machine learning approaches are being investigated to help improve the effectiveness and speed of multiple stages of the drug discovery pipeline. Of these, those that use Knowledge Graphs (KG) have promise in many tasks, including drug repurposing, drug toxicity prediction and target gene-disease prioritization. In a drug discovery KG, crucial elements including genes, diseases and drugs are represented as entities, while relationships between them indicate an interaction. However, to construct high-quality KGs, suitable data are required. In this review, we detail publicly available sources suitable for use in constructing drug discovery focused KGs. We aim to help guide machine learning and KG practitioners who are interested in applying new techniques to the drug discovery field, but who may be unfamiliar with the relevant data sources. The datasets are selected via strict criteria, categorized according to the primary type of information contained within and are considered based upon what information could be extracted to build a KG. We then present a comparative analysis of existing public drug discovery KGs and an evaluation of selected motivating case studies from the literature. Additionally, we raise numerous and unique challenges and issues associated with the domain and its datasets, while also highlighting key future research directions. We hope this review will motivate KGs use in solving key and emerging questions in the drug discovery domain.
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| 8. |
- Camarasa, Clara, et al.
(författare)
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Energy-efficient retrofit measures (EERM) in residential buildings: An application of discrete choice modelling
- 2021
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Ingår i: Buildings. - : MDPI AG. - 2075-5309. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- Cross-country evidence on the adoption of energy-efficient retrofit measures (EERMs) in residential buildings is critical to supporting the development of national and pan-European policies aimed at fostering the energy performance upgrade of the building stock. In this light, the aim of this paper is to advance in the understanding of the probability of certain EERMs taking place in eight EU countries, according to a set of parameters, such as building typology, project types, and motivation behind the project. Using these parameters collected via a multi-country online survey, a set of discrete-choice (conditional logit) models are estimated on the probability of selecting a choice of any combination of 33 EERMs across the sampled countries. Results show that actions related to the building envelope are the most often-addressed across countries and single building elements or technology measures have a higher probability of being implemented. The modelling framework developed in this study contributes to the scientific community in three ways: (1) establishing an empirical relationship among EERMs and project (i.e., retrofit and deep retrofit), (2) identifying commonalities and differences across the selected countries, and (3) quantifying the probabilities and market shares of various EERMs.
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| 9. |
- Chávez de Paz, Luis Eduardo, et al.
(författare)
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Oral bacteria in biofilms exhibit slow reactivation from nutrient deprivation
- 2008
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Ingår i: Microbiology. - : Microbiology Society. - 1350-0872 .- 1465-2080. ; 154, s. 1927-1938
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Tidskriftsartikel (refereegranskat)abstract
- The ability of oral bacteria to enter a non-growing state is believed to be an important mechanism for survival in the starved micro-environments of the oral cavity. In this study, we examined the reactivation of nutrient-deprived cells of two oral bacteria in biofilms, Streptococcus anginosus and Lactobacillus salivarius. Non-growing cells were generated by incubation in 10 mM potassium phosphate buffer for 24 h and the results were compared to those of planktonic cultures. When both types of cells were shifted from a rich, peptone-yeast extract-glucose (PYG) medium to buffer for 24 h, dehydrogenase and esterase activity measured by the fluorescent dyes 5-cyano-2,3-ditolyl-tetrazolium chloride (CTC) and fluorescein diacetate (FDA), respectively, was absent in both species. However, the membranes of the vast majority of nutrient-deprived cells remained intact as assessed by LIVE/DEAD staining. Metabolic reactivation of the nutrient-deprived biofilm cells was not observed for at least 48 h following addition of fresh PYG medium, whereas the non-growing planktonic cultures of the same two strains were in rapid growth in less than 2 h. At 72 h, the S. anginosus biofilm cells had recovered 78 % of the dehydrogenase activity and 61 % of the esterase activity and the biomass mm(-2) had increased by 30-35 %. With L. salivarius at 72 h, the biofilms had recovered 56 % and 75 % of dehydrogenase and esterase activity, respectively. Reactivation of both species in biofilms was enhanced by removal of glucose from PYG, and S. anginosus cells were particularly responsive to yeast extract (YE) medium. The data suggest that the low reactivity of non-growing biofilm cells to the introduction of fresh nutrients may be a survival strategy employed by micro-organisms in the oral cavity.
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| 10. |
- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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