| 1. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 2. |
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| 3. |
- Cloarec, Olivier, et al.
(författare)
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Evaluation of the Orthogonal Projection on Latent Structure Model Limitations Caused by Chemical Shift Variability and Improved Visualization of Biomarker Changes in 1H NMR Spectroscopic Metabonomic Studies
- 2005
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 77:2, s. 517-26
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Tidskriftsartikel (refereegranskat)abstract
- In general, applications of metabonomics using biofluid NMR spectroscopic analysis for probing abnormal biochemical profiles in disease or due to toxicity have all relied on the use of chemometric techniques for sample classification. However, the well-known variability of some chemical shifts in 1H NMR spectra of biofluids due to environmental differences such as pH variation, when coupled with the large number of variables in such spectra, has led to the situation where it is necessary to reduce the size of the spectra or to attempt to align the shifting peaks, to get more robust and interpretable chemometric models. Here, a new approach that avoids this problem is demonstrated and shows that, moreover, inclusion of variable peak position data can be beneficial and can lead to useful biochemical information. The interpretation of chemometric models using combined back-scaled loading plots and variable weights demonstrates that this peak position variation can be handled successfully and also often provides additional information on the physicochemical variations in metabonomic data sets.
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| 4. |
- Cloarec, Olivier, et al.
(författare)
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Statistical Total Correlation Spectroscopy: An Exploratory Approach for Latent Biomarker Identification from Metabolic 1H NMR Data Sets
- 2005
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 77:5, s. 1282-89
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Tidskriftsartikel (refereegranskat)abstract
- We describe here the implementation of the statistical total correlation spectroscopy (STOCSY) analysis method for aiding the identification of potential biomarker molecules in metabonomic studies based on NMR spectroscopic data. STOCSY takes advantage of the multicollinearity of the intensity variables in a set of spectra (in this case 1H NMR spectra) to generate a pseudo-two-dimensional NMR spectrum that displays the correlation among the intensities of the various peaks across the whole sample. This method is not limited to the usual connectivities that are deducible from more standard two-dimensional NMR spectroscopic methods, such as TOCSY. Moreover, two or more molecules involved in the same pathway can also present high intermolecular correlations because of biological covariance or can even be anticorrelated. This combination of STOCSY with supervised pattern recognition and particularly orthogonal projection on latent structure-discriminant analysis (O-PLS-DA) offers a new powerful framework for analysis of metabonomic data. In a first step O-PLS-DA extracts the part of NMR spectra related to discrimination. This information is then cross-combined with the STOCSY results to help identify the molecules responsible for the metabolic variation. To illustrate the applicability of the method, it has been applied to 1H NMR spectra of urine from a metabonomic study of a model of insulin resistance based on the administration of a carbohydrate diet to three different mice strains (C57BL/6Oxjr, BALB/cOxjr, and 129S6/SvEvOxjr) in which a series of metabolites of biological importance can be conclusively assigned and identified by use of the STOCSY approach.
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| 5. |
- Ding, Li, et al.
(författare)
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Somatic mutations affect key pathways in lung adenocarcinoma
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 455:7216, s. 1069-1075
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Tidskriftsartikel (refereegranskat)abstract
- Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.
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| 6. |
- Goodacre, Royston, et al.
(författare)
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Proposed minimum reporting standards for data analysis in metabolomics
- 2007
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Ingår i: Metabolomics. - : Springer Science and Business Media LLC. - 1573-3882 .- 1573-3890. ; 3, s. 231-41
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Tidskriftsartikel (refereegranskat)abstract
- The goal of this group is to define the reporting requirements associated with the statistical analysis (including univariate, multivariate, informatics, machine learning etc.) of metabolite data with respect to other measured/collected experimental data (often called metadata). These definitions will embrace as many aspects of a complete metabolomics study as possible at this time. In chronological order this will include: Experimental Design, both in terms of sample collection/matching, and data acquisition scheduling of samples through whichever spectroscopic technology used; Deconvolution (if required); Pre-processing, for example, data cleaning, outlier detection, row/column scaling, or other transformations; Definition and parameterization of subsequent visualizations and Statistical/Machine learning Methods applied to the dataset; If required, a clear definition of the Model Validation Scheme used (including how data are split into training/validation/test sets); Formal indication on whether the data analysis has been Independently Tested (either by experimental reproduction, or blind hold out test set). Finally, data interpretation and the visual representations and hypotheses obtained from the data analyses.
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| 7. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
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Ingår i: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
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Forskningsöversikt (refereegranskat)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.
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| 8. |
- Malkoch, Michael, et al.
(författare)
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Synthesis of well-defined hydrogel networks using Click chemistry
- 2006
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Ingår i: Chemical Communications. - 1359-7345 .- 1364-548X. ; :26, s. 2774-2776
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Tidskriftsartikel (refereegranskat)abstract
- New PEG-based hydrogel materials have been synthesized by Click chemistry and shown to result in well-defined networks having significantly improved mechanical properties; the selectivity of the azide/ acetylene coupling reaction also allows for the incorporation of various additives and functional groups leading to chemical tailoring of the hydrogels.
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| 9. |
- Rahpeymai, Yalda, 1977, et al.
(författare)
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Complement: a novel factor in basal and ischemia-induced neurogenesis.
- 2006
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Ingår i: The EMBO journal. - : Wiley. - 0261-4189 .- 1460-2075. ; 25:6, s. 1364-74
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Tidskriftsartikel (refereegranskat)abstract
- Through its involvement in inflammation, opsonization, and cytolysis, the complement protects against infectious agents. Although most of the complement proteins are synthesized in the central nervous system (CNS), the role of the complement system in the normal or ischemic CNS remains unclear. Here we demonstrate for the first time that neural progenitor cells and immature neurons express receptors for complement fragments C3a and C5a (C3a receptor (C3aR) and C5a receptor). Mice that are deficient in complement factor C3 (C3(-/-)) lack C3a and are unable to generate C5a through proteolytic cleavage of C5 by C5-convertase. Intriguingly, basal neurogenesis is decreased both in C3(-/-) mice and in mice lacking C3aR or mice treated with a C3aR antagonist. The C3(-/-) mice had impaired ischemia-induced neurogenesis both in the subventricular zone, the main source of neural progenitor cells in adult brain, and in the ischemic region, despite normal proliferative response and larger infarct volumes. Thus, in the adult mammalian CNS, complement activation products promote both basal and ischemia-induced neurogenesis.
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| 10. |
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