The Experts below are selected from a list of 265167 Experts worldwide ranked by ideXlab platform
Bernard Jegou - One of the best experts on this subject based on the ideXlab platform.
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a Critical Assessment of the endocrine susceptibility of the human testis to phthalates from fetal life to adulthood
Human Reproduction Update, 2014Co-Authors: Oceane Albert, Bernard JegouAbstract:results: We provide an up-to-date exhaustive, comparative and Critical Assessment of both in vivo and in vitro studies undertaken to explore the effects of phthalates on the human testis from fetal life to adulthood. These results are compared and discussed in the light of the key data reported in the literature for mice and rats. conclusions: The current literature highlights the fact that (i) there is a huge difference between the number of studies performed in animals and in humans, with many fewer for humans; (ii) there are differences in the way rats, mice, primates and humans respond to phthalates, for reasons that need to be further explored; (iii) more work is required to clarify the contradictions, in the few existing human epidemiological studies at all stages of development, which may be partly explained by varying methods of exposure Assessment; (iv) in accordance with recent findings in rodents, it cannot be excluded that transgenerational effects of phthalates and/or epigenetic changes exist in humans; (v) a number of methodological limitations need to be solved for the in vitro and xenografting models using human fetal testis to fulfil their 'missing
Ivan Gregor - One of the best experts on this subject based on the ideXlab platform.
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Critical Assessment of metagenome interpretation a benchmark of metagenomics software
Nature Methods, 2017Co-Authors: Alexander Sczyrba, Johannes Dröge, Peter Hofmann, Peter Belmann, David Koslicki, Stefan Janssen, Ivan GregorAbstract:Methods for assembly, taxonomic profiling and binning are key to interpreting metagenome data, but a lack of consensus about benchmarking complicates performance Assessment. The Critical Assessment of Metagenome Interpretation (CAMI) challenge has engaged the global developer community to benchmark their programs on highly complex and realistic data sets, generated from ∼700 newly sequenced microorganisms and ∼600 novel viruses and plasmids and representing common experimental setups. Assembly and genome binning programs performed well for species represented by individual genomes but were substantially affected by the presence of related strains. Taxonomic profiling and binning programs were proficient at high taxonomic ranks, with a notable performance decrease below family level. Parameter settings markedly affected performance, underscoring their importance for program reproducibility. The CAMI results highlight current challenges but also provide a roadmap for software selection to answer specific research questions.
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Critical Assessment of metagenome interpretation a benchmark of computational metagenomics software
bioRxiv, 2017Co-Authors: Alexander Sczyrba, Johannes Dröge, Peter Hofmann, Peter Belmann, David Koslicki, Stefan Janssen, Ivan Gregor, Stephan Majda, Jessika Fiedler, Eik DahmsAbstract:In metagenome analysis, computational methods for assembly, taxonomic profiling and binning are key components facilitating downstream biological data interpretation. However, a lack of consensus about benchmarking datasets and evaluation metrics complicates proper performance Assessment. The Critical Assessment of Metagenome Interpretation (CAMI) challenge has engaged the global developer community to benchmark their programs on datasets of unprecedented complexity and realism. Benchmark metagenomes were generated from newly sequenced ~700 microorganisms and ~600 novel viruses and plasmids, including genomes with varying degrees of relatedness to each other and to publicly available ones and representing common experimental setups. Across all datasets, assembly and genome binning programs performed well for species represented by individual genomes, while performance was substantially affected by the presence of related strains. Taxonomic profiling and binning programs were proficient at high taxonomic ranks, with a notable performance decrease below the family level. Parameter settings substantially impacted performances, underscoring the importance of program reproducibility. While highlighting current challenges in computational metagenomics, the CAMI results provide a roadmap for software selection to answer specific research questions.
Oceane Albert - One of the best experts on this subject based on the ideXlab platform.
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a Critical Assessment of the endocrine susceptibility of the human testis to phthalates from fetal life to adulthood
Human Reproduction Update, 2014Co-Authors: Oceane Albert, Bernard JegouAbstract:results: We provide an up-to-date exhaustive, comparative and Critical Assessment of both in vivo and in vitro studies undertaken to explore the effects of phthalates on the human testis from fetal life to adulthood. These results are compared and discussed in the light of the key data reported in the literature for mice and rats. conclusions: The current literature highlights the fact that (i) there is a huge difference between the number of studies performed in animals and in humans, with many fewer for humans; (ii) there are differences in the way rats, mice, primates and humans respond to phthalates, for reasons that need to be further explored; (iii) more work is required to clarify the contradictions, in the few existing human epidemiological studies at all stages of development, which may be partly explained by varying methods of exposure Assessment; (iv) in accordance with recent findings in rodents, it cannot be excluded that transgenerational effects of phthalates and/or epigenetic changes exist in humans; (v) a number of methodological limitations need to be solved for the in vitro and xenografting models using human fetal testis to fulfil their 'missing
John Moult - One of the best experts on this subject based on the ideXlab platform.
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abstract lb 250 the Critical Assessment of genome interpretation a community experiment that informs use of methods for germline cancer variant impact prediction
Cancer Research, 2020Co-Authors: Constantina Bakolitsa, John Moult, Gaia Andreoletti, Roger A Hoskins, Predrag Radivojac, Steven E Brenner, Cagi ParticipantsAbstract:Interpretation of genomic variation plays an essential role in the analysis of cancer and monogenic disease, with applications ranging from basic research to clinical decisions. Yet the field lacks a clear consensus on the appropriate level of confidence to place in variant impact and interpretation methods, for both well-established oncogenes as well as less understood genes. The Critical Assessment of Genome Interpretation (CAGI, \9kā-jē\) is a community experiment to objectively assess computational methods for predicting the phenotypic impacts of genomic variation. CAGI participants are provided genetic variants from genes like BRCA1 and TP53, and make blind predictions of resulting phenotype. Independent assessors evaluate the predictions by comparing them against experimental and clinical data. Each of the five CAGI editions over the past decade has revealed new aspects of the methods, and there has been significant progress in several areas. CAGI challenges from cancer case-control studies have revealed that missense methods tend to correlate better with each other than with experiment (RAD50 breast cancer challenge), an observation also encountered in other CAGI missense challenges. Bespoke approaches can often enhance performance, as seen in the p16 challenge involving variants of unknown significance in familial malignant melanoma, while the p53 reactivation challenge showed that biophysical simulations can occasionally make exceptional predictions. Method performance can vary greatly, even within proteins of the same complex (MRN complex breast cancer challenge). CAGI shows promise meta-predictors (BRCA1 and BRCA2 challenges). Interpretation of some non-coding variants shows promise, as exemplified by the TP53 splicing challenge. Top missense prediction methods are highly statistically significant, but individual variant accuracy is limited. Data from CAGI, including the CHEK2 challenge, were recently presented within the ClinGen Sequence Variant Interpretation working group to explore increasing evidence weighting of computational methods, when those methods demonstrate sufficient reliability for a specific gene or disorder. CAGI results suggest that running multiple uncalibrated methods and considering their consensus may result in undue confidence, so we advise against this. Overall, CAGI has helped establishing the state of art in genome interpretation, encouraged new methodological developments, and informed the clinical application of computational predictors. Results from previous CAGI experiments have been described in two special issues of Human Mutation (vol. 38(9) and vol. 40(9)). Detailed information about CAGI may be found at https://genomeinterpretation.org. Citation Format: Constantina Bakolitsa, Gaia Andreoletti, Roger Hoskins, Predrag Radivojac, John Moult, Steven Brenner, CAGI participants. The Critical Assessment of Genome Interpretation: A community experiment that informs use of methods for germline cancer variant impact prediction [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-250.
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Critical Assessment of methods of protein structure prediction casp round xiii
Proteins, 2019Co-Authors: Andriy Kryshtafovych, Torsten Schwede, Krzysztof Fidelis, Maya Topf, John MoultAbstract:CASP (Critical Assessment of structure prediction) assesses the state of the art in modeling protein structure from amino acid sequence. The most recent experiment (CASP13 held in 2018) saw dramatic progress in structure modeling without use of structural templates (historically "ab initio" modeling). Progress was driven by the successful application of deep learning techniques to predict inter-residue distances. In turn, these results drove dramatic improvements in three-dimensional structure accuracy: With the proviso that there are an adequate number of sequences known for the protein family, the new methods essentially solve the long-standing problem of predicting the fold topology of monomeric proteins. Further, the number of sequences required in the alignment has fallen substantially. There is also substantial improvement in the accuracy of template-based models. Other areas-model refinement, accuracy estimation, and the structure of protein assemblies-have again yielded interesting results. CASP13 placed increased emphasis on the use of sparse data together with modeling and chemical crosslinking, SAXS, and NMR all yielded more mature results. This paper summarizes the key outcomes of CASP13. The special issue of PROTEINS contains papers describing the CASP13 Assessments in each modeling category and contributions from the participants.
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Critical Assessment of methods of protein structure prediction casp round xii
Proteins, 2018Co-Authors: John Moult, Torsten Schwede, Krzysztof Fidelis, Andriy Kryshtafovych, Anna TramontanoAbstract:This article reports the outcome of the 12th round of Critical Assessment of Structure Prediction (CASP12), held in 2016. CASP is a community experiment to determine the state of the art in modeling protein structure from amino acid sequence. Participants are provided sequence information and in turn provide protein structure models and related information. Analysis of the submitted structures by independent assessors provides a comprehensive picture of the capabilities of current methods, and allows progress to be identified. This was again an exciting round of CASP, with significant advances in 4 areas: (i) The use of new methods for predicting three-dimensional contacts led to a two-fold improvement in contact accuracy. (ii) As a consequence, model accuracy for proteins where no template was available improved dramatically. (iii) Models based on a structural template showed overall improvement in accuracy. (iv) Methods for estimating the accuracy of a model continued to improve. CASP continued to develop new areas: (i) Assessing methods for building quaternary structure models, including an expansion of the collaboration between CASP and CAPRI. (ii) Modeling with the aid of experimental data was extended to include SAXS data, as well as again using chemical cross-linking information. (iii) A team of assessors evaluated the suitability of models for a range of applications, including mutation interpretation, analysis of ligand binding properties, and identification of interfaces. This article describes the experiment and summarizes the results. The rest of this special issue of PROTEINS contains papers describing CASP12 results and Assessments in more detail.
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Critical Assessment of methods of protein structure prediction (CASP)--round x.
Proteins - Structure Function and Bioinformatics, 2014Co-Authors: John Moult, Torsten Schwede, Krzysztof Fidelis, Andriy Kryshtafovych, Anna TramontanoAbstract:This article is an introduction to the special issue of the journal PROTEINS, dedicated to the tenth Critical Assessment of Structure Prediction (CASP) experiment to assess the state of the art in protein structure modeling. The article describes the conduct of the experiment, the categories of prediction included, and outlines the evaluation and Assessment procedures. The 10 CASP experiments span almost 20 years of progress in the field of protein structure modeling, and there have been enormous advances in methods and model accuracy in that period. Notable in this round is the first sustained improvement of models with refinement methods, using molecular dynamics. For the first time, we tested the ability of modeling methods to make use of sparse experimental three-dimensional contact information, such as may be obtained from new experimental techniques, with encouraging results. On the other hand, new contact prediction methods, though holding considerable promise, have yet to make an impact in CASP testing. The nature of CASP targets has been changing in recent CASPs, reflecting shifts in experimental structural biology, with more irregular structures, more multi-domain and multi-subunit structures, and less standard versions of known folds. When allowance is made for these factors, we continue to see steady progress in the overall accuracy of models, particularly resulting from improvement of non-template regions.
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Critical Assessment of methods of protein structure prediction casp round ix
Proteins, 2011Co-Authors: John Moult, Krzysztof Fidelis, Andriy Kryshtafovych, Anna TramontanoAbstract:This article is an introduction to the special issue of the journal PROTEINS, dedicated to the ninth Critical Assessment of Structure Prediction (CASP) experiment to assess the state of the art in protein structure modeling. The article describes the conduct of the experiment, the categories of prediction included, and outlines the evaluation and Assessment procedures. Methods for modeling protein structure continue to advance, although at a more modest pace than in the early CASP experiments. CASP developments of note are indications of improvement in model accuracy for some classes of target, an improved ability to choose the most accurate of a set of generated models, and evidence of improvement in accuracy for short "new fold" models. In addition, a new analysis of regions of models not derivable from the most obvious template structure has revealed better performance than expected.
Riccardo Rebonato - One of the best experts on this subject based on the ideXlab platform.
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A Critical Assessment of Libertarian Paternalism
Journal of Consumer Policy, 2014Co-Authors: Riccardo RebonatoAbstract:This paper tries to assess to what extent libertarian paternalism lives up to its libertarian credentials, and whether this “softer” version of paternalism is more or less desirable than the traditional, more coercive (but also more transparent) form. Since much is made in the libertarian paternalistic programme of the ease of reversibility of “nudges,” it is argued that the distinction between effective and nominal ability to reverse a nudge is more important than its theoretical ease of reversibility—the more so, if anchoring, framing and status quo bias are as powerful as the libertarian paternalists maintain. If the libertarian paternalistic nudges are effective, but not always transparent, it is argued that this raises some questions (which do not seem to have been adequately addressed in the current literature) about the legitimacy of the interventions; about how the true preferences of the “consumer” can be guessed by the choice architect (and the role played by rationality in this process) and about the effective respect of her autonomy. Finally, this paper highlights some alternatives to “nudging” which place a greater emphasis on the full process of choice—rather than just on its outcomes—and can therefore better preserve true autonomy of choice.
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a Critical Assessment of libertarian paternalism
2013Co-Authors: Riccardo RebonatoAbstract:In this note I concisely present the main arguments advanced in "Taking Liberties" (2012). In particular, I look at the philosophical roots of libertarian paternalism. I examine whether the claims that it constitutes the "real Third Way" and that it always should be preferred to 'harder' forms of paternalism are justified, and I propose that interventions aimed at improving, rather than 'nudging', human cognitive abilities may be more consonant with a truly libertarian programme. I also discuss whether the easy reversibility of 'nudges', which is often mentioned as one of its most desirable features, is truly as important and effective as generally thought.
