| 1. |
- Hillier, Ladeana W, et al.
(författare)
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Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
- 2004
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
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Tidskriftsartikel (refereegranskat)abstract
- We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
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| 2. |
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| 3. |
- Augustin, Ingo, et al.
(författare)
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HEP Applications Evaluation of the EDG Testbed and Middleware
- 2003
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Konferensbidrag (refereegranskat)abstract
- Workpackage 8 of the European Datagrid project was formed in January 2001 with representatives from the four LHC experiments, and with experiment independent people from five of the six main EDG partners. In September 2002 WP8 was strengthened by the addition of effort from BaBar and D0. The original mandate of WP8 was, following the definition of short- and long-term requirements, to port experiment software to the EDG middleware and testbed environment. A major additional activity has been testing the basic functionality and performance of this environment. This paper reviews experiences and evaluations in the areas of job submission, data management, mass storage handling, information systems and monitoring. It also comments on the problems of remote debugging, the portability of code, and scaling problems with increasing numbers of jobs, sites and nodes. Reference is made to the pioneeering work of Atlas and CMS in integrating the use of the EDG Testbed into their data challenges. A forward look is made to essential software developments within EDG and to the necessary cooperation between EDG and LCG for the LCG prototype due in mid 2003.
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| 4. |
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| 5. |
- Clemens, John, et al.
(författare)
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Development of pathogenicity-driven definitions of outcomes for a field trial of a killed oral vaccine against enterotoxigenic Escherichia coli in Egypt: application of an evidence-based method
- 2004
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Ingår i: J Infect Dis. ; 189:12, s. 2299-307
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To design an efficacy trial of a killed oral vaccine against enterotoxigenic Escherichia coli (ETEC) diarrhea in Egyptian children, we derived for ETEC diarrhea an empirical definition that increased the probability that diarrhea associated with excretion of ETEC was caused by the detected ETEC. METHODS: We conducted a cohort study of 397 Egyptian children <24 months old and monitored them until they were 3 years old. Vaccine-preventable (VP) ETEC was defined as ETEC expressing >/=1 of the toxin- (heat-labile [LT] toxin) and colonization-factor antigens (CFA I, II, and IV) in the vaccine. RESULTS: Although fecal excretion of VP-ETEC was highly associated with diarrhea, excretion of LT-ETEC per se was not related to diarrhea (adjusted odds ratio [OR(A)], 1.16 [95% confidence interval [CI], 0.90-1.49]). The fecal excretion of antigenic types of VP-ETEC other than LT-ETEC (non-LT VP-ETEC) was highly associated with diarrheal symptoms (OR(A), 3.91 [95% CI, 2.78-5.49]; P<.001), and this association was greater for nonbloody than for bloody diarrhea. CONCLUSIONS: Because the vaccine had been anticipated to protect primarily against symptomatic ETEC diarrhea, these results indicate that the primary-outcome definition of ETEC diarrhea for the trial should be restricted to nonbloody diarrheal episodes associated with fecal excretion of non-LT VP-ETEC.
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| 6. |
- Clish, Clary B., et al.
(författare)
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Integrative biological analysis of the APOE*3-leiden transgenic mouse
- 2004
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Ingår i: Omics. - : Mary Ann Liebert. - 1536-2310 .- 1557-8100. ; 8:1, s. 3-13
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Tidskriftsartikel (refereegranskat)abstract
- Integrative (or systems biology) is a new approach to analyzing biological entities as integrated systems of genetic, genomic, protein, metabolite, cellular, and pathway events that are in flux and interdependent. Here, we demonstrate the application of intregrative biological analysis to a mammalian disease model, the apolipoprotein E3-Leiden (APO*E3) transgenic mouse. Mice selected for the study were fed a normal chow diet and sacrificed at 9 weeks of age-conditions under which they develop only mild type I and II atherosclerotic lesions. Hepatic mRNA expression analysis showed a 25% decrease in APO A1 and a 43% increase in liver fatty acid binding protein expression between transgenic and wild type control mice, while there was no change in PPAR-alpha expression. On-line high performance liquid chromatography-mass spectrometry quantitative profiling of tryptic digests of soluble liver proteins and liver lipids, coupled with principle component analysis, enabled rapid identification of early protein and metabolite markers of disease pathology. These included a 44% increase in L-FABP in transgenic animals compared to controls, as well as an increase in triglycerides and select bioactive lysophosphatidylcholine species. A correlation analysis of identified genes, proteins, and lipids was used to construct an interaction network. Taken together, these results indicate that integrative biology is a powerful tool for rapid identification of early markers and key components of pathophysiologic processes, and constitute the first application of this approach to a mammalian system.
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| 7. |
- Davidov, Eugene, et al.
(författare)
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Methods for the differential integrative omic analysis of plasma from a transgenic disease animal model
- 2004
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Ingår i: Omics. - : Mary Ann Liebert. - 1536-2310 .- 1557-8100. ; 8:4, s. 267-288
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Tidskriftsartikel (refereegranskat)abstract
- Multitiered quantitative analysis of biological systems is rapidly becoming the desired approach to study hierarchical functional interactions between proteins and metabolites. We describe here a novel systematic approach to analyze organisms with complex metabolic regulatory networks. By using precise analytical methods to measure biochemical constituents and their relative abundance in whole plasma of transgenic ApoE*3-Leiden mice and an isogenic wild-type control group, simultaneous snapshots of metabolic and protein states were obtained. Novel data processing and multivariate analysis tools such as Impurity Resolution Software (IMPRESS) and Windows-based linear fit program (WINLIN) were used to compare protein and metabolic profiles in parallel. Canonical correlations of the resulting data show quantitative relationships between heterogeneous components in the TG animals. These results, obtained solely from whole plasma analysis allowed us, in a rapid manner, to corroborate previous findings as well as find new events pertaining to dominant and peripheral events in lipoprotein metabolism of a genetically modified mammalian organism in relation to ApoE3, a key mediator of lipoprotein metabolism.
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| 9. |
- Liljelind, Ingrid E, et al.
(författare)
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Comparison of self-assessment and expert assessment of occupational exposure to chemicals
- 2001
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Ingår i: Scandinavian Journal of Work, Environment and Health. - : Tyoterveyslaitos, Finnish Institute of Occupational Health. - 0355-3140 .- 1795-990X. ; 27:5, s. 311-317
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Occupational assessments of chemical exposure are often inadequate because of difficulties in obtaining sufficient numbers of measurements by trained professionals (experts). The objective of this study was to determine whether workers can provide unbiased data via self-assessments of exposure facilitated by the use of simple passive monitors for personal sampling.METHODS: Untrained workers obtained personal measurements of their exposures to gaseous contaminants (terpenes in sawmills and styrene in reinforced plastics factories) with passive monitors and written instructions. To study the validity of the self-assessments, an occupational hygienist performed exposure measurements on the same occupational groups after the workers had obtained two or more measurements independently. The potential bias of the self-assessments was evaluated by comparing the self-assessments with the expert assessments in mixed-effects statistical models.RESULTS: A total of 153 terpene (97 self and 56 expert) and 216 styrene (159 self and 57 expert) measurements were obtained from four sawmills and six reinforced plastics factories, respectively. No significant differences in the geometric mean exposures were observed between the self-assessments and the expert assessments in 3 of 4 sawmills and 5 of 6 reinforced plastics factories (P > 0.10). The potential bias of the self-assessments of exposure ranged from less than 0.1% to 102% and was less than 17% in 9 of the 10 groups investigated.CONCLUSIONS: The results indicate that untrained, unsupervised workers are able to collect consistently unbiased exposure data by employing currently available passive monitors.
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| 10. |
- Oresic, Matej, 1967-, et al.
(författare)
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Phenotype characterisation using integrated gene transcript, protein and metabolite profiling
- 2004
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Ingår i: Applied bioinformatics. - : Adis International Ltd.. - 1175-5636. ; 3:4, s. 205-217
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Tidskriftsartikel (refereegranskat)abstract
- Multifactorial diseases present a significant challenge for functional genomics. Owing to their multiple compartmental effects and complex biomolecular activities, such diseases cannot be adequately characterised by changes in single components, nor can pathophysiological changes be understood by observing gene transcripts alone. Instead, a pattern of subtle changes is observed in multifactorial diseases across multiple tissues and organs with complex associations between corresponding gene, protein and metabolite levels. This article presents methods for exploratory and integrative analysis of pathophysiological changes at the biomolecular level. In particular, novel approaches are introduced for the following challenges: (i) data processing and analysis methods for proteomic and metabolomic data obtained by electrospray ionisation (ESI) liquid chromatography-tandem mass spectrometry (LC/MS); (ii) association analysis of integrated gene, protein and metabolite patterns that are most descriptive of pathophysiological changes; and (iii) interpretation of results obtained from association analyses in the context of known biological processes. These novel approaches are illustrated with the apolipoprotein E3-Leiden transgenic mouse model, a commonly used model of atherosclerosis. We seek to gain insight into the early responses of disease onset and progression by determining and identifying--well in advance of pathogenic manifestations of disease--the sets of gene transcripts, proteins and metabolites, along with their putative relationships in the transgenic model and associated wild-type cohort. Our results corroborate previous findings and extend predictions for three processes in atherosclerosis: aberrant lipid metabolism, inflammation, and tissue development and maintenance.
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