Human metabolic individuality in biomedical and pharmaceutical research.

Genome-wide association studies (GWAS) have identified many risk loci for complex diseases, but effect sizes are typically small and information on the underlying biological processes is often lacking. Associations with metabolic traits as functional intermediates can overcome these problems and potentially inform individualized therapy. Here we report a comprehensive analysis of genotype-dependent metabolic phenotypes using a GWAS with non-targeted metabolomics. We identified 37 genetic loci associated with blood metabolite concentrations, of which 25 show effect sizes that are unusually high for GWAS and account for 10-60% differences in metabolite levels per allele copy. Our associations provide new functional insights for many disease-related associations that have been reported in previous studies, including those for cardiovascular and kidney disorders, type 2 diabetes, cancer, gout, venous thromboembolism and Crohn's disease. The study advances our knowledge of the genetic basis of metabolic individuality in humans and generates many new hypotheses for biomedical and pharmaceutical research.

Animal Toxins: How is Complexity Represented in Databases?

Peptide toxins synthesized by venomous animals have been extensively studied in the last decades. To be useful to the scientific community, this knowledge has been stored, annotated and made easy to retrieve by several databases. The aim of this article is to present what type of information users can access from each database. ArachnoServer and ConoServer focus on spider toxins and cone snail toxins, respectively. UniProtKB, a generalist protein knowledgebase, has an animal toxin-dedicated annotation program that includes toxins from all venomous animals. Finally, the ATDB metadatabase compiles data and annotations from other databases and provides toxin ontology.

Web-based reference databases and subject gateways to locate current research information in agricultural and food sciences : a Finnish perspective

Selostus: Maatalous- ja elintarviketieteiden www-pohjaiset viitetietokannat ja aihehakemistot - suomalaisen tiedonetsijän näkökulma

A process for mining science & technology documents databases, illustrated for the case of "knowledge discovery and data mining"

This paper presents a process of mining research & development abstract databases to profile current status and to project potential developments for target technologies, The process is called "technology opportunities analysis." This article steps through the process using a sample data set of abstracts from the INSPEC database on the topic o "knowledge discovery and data mining." The paper offers a set of specific indicators suitable for mining such databases to understand innovation prospects. In illustrating the uses of such indicators, it offers some insights into the status of knowledge discovery research*.

trome, trEST and trGEN: databases of predicted protein sequences.

We previously introduced two new protein databases (trEST and trGEN) of hypothetical protein sequences predicted from EST and HTG sequences, respectively. Here, we present the updates made on these two databases plus a new database (trome), which uses alignments of EST data to HTG or full genomes to generate virtual transcripts and coding sequences. This new database is of higher quality and since it contains the information in a much denser format it is of much smaller size. These new databases are in a Swiss-Prot-like format and are updated on a weekly basis (trEST and trGEN) or every 3 months (trome). They can be downloaded by anonymous ftp from ftp://ftp.isrec.isb-sib.ch/pub/databases.

La cohorte sepsis lausannoise: une opportunité de développer la recherche dans le Réseau latin de médecine intensive [Lausanne Cohort of septic patients as an opportunity to develop multidisciplinary research within the Swiss Latin Network of Intensive Care Medicine]

Despite recent medical progresses in patient support, the mortality of sepsis remains high. Recently, new supporting strategies were proposed to improve outcome. Whereas such strategies are currently considered as standard of care, their real impact on mortality, morbidity, length of stay, and hence, health care resources utilization has been only weakly evaluated so far. Obviously, there is a critical need for epidemiologic surveys of sepsis to better address these major issues. The Lausanne Cohort of septic patients aims at building a large clinical, biological and microbiological database that will be used as a multidisciplinary research platform to study the various pathogenic mechanisms of sepsis in collaboration with the various specialists. This could be an opportunity to strengthen the collaboration within the Swiss Latin network of Intensive Care Medicine.

Swiss EMBnet node web server.

EMBnet is a consortium of collaborating bioinformatics groups located mainly within Europe (http://www.embnet.org). Each member country is represented by a 'node', a group responsible for the maintenance of local services for their users (e.g. education, training, software, database distribution, technical support, helpdesk). Among these services a web portal with links and access to locally developed and maintained software is essential and different for each node. Our web portal targets biomedical scientists in Switzerland and elsewhere, offering them access to a collection of important sequence analysis tools mirrored from other sites or developed locally. We describe here the Swiss EMBnet node web site (http://www.ch.embnet.org), which presents a number of original services not available anywhere else.

Biomedical risk assessment as an aid for smoking cessation.

BACKGROUND: A possible strategy for increasing smoking cessation rates could be to provide smokers who have contact with healthcare systems with feedback on the biomedical or potential future effects of smoking, e.g. measurement of exhaled carbon monoxide (CO), lung function, or genetic susceptibility to lung cancer. OBJECTIVES: To determine the efficacy of biomedical risk assessment provided in addition to various levels of counselling, as a contributing aid to smoking cessation. SEARCH METHODS: For the most recent update, we searched the Cochrane Collaboration Tobacco Addiction Group Specialized Register in July 2012 for studies added since the last update in 2009. SELECTION CRITERIA: Inclusion criteria were: a randomized controlled trial design; subjects participating in smoking cessation interventions; interventions based on a biomedical test to increase motivation to quit; control groups receiving all other components of intervention; an outcome of smoking cessation rate at least six months after the start of the intervention. DATA COLLECTION AND ANALYSIS: Two assessors independently conducted data extraction on each paper, with disagreements resolved by consensus. Results were expressed as a relative risk (RR) for smoking cessation with 95% confidence intervals (CI). Where appropriate, a pooled effect was estimated using a Mantel-Haenszel fixed-effect method. MAIN RESULTS: We included 15 trials using a variety of biomedical tests. Two pairs of trials had sufficiently similar recruitment, setting and interventions to calculate a pooled effect; there was no evidence that carbon monoxide (CO) measurement in primary care (RR 1.06, 95% CI 0.85 to 1.32) or spirometry in primary care (RR 1.18, 95% CI 0.77 to 1.81) increased cessation rates. We did not pool the other 11 trials due to the presence of substantial clinical heterogeneity. Of the remaining 11 trials, two trials detected statistically significant benefits: one trial in primary care detected a significant benefit of lung age feedback after spirometry (RR 2.12, 95% CI 1.24 to 3.62) and one trial that used ultrasonography of carotid and femoral arteries and photographs of plaques detected a benefit (RR 2.77, 95% CI 1.04 to 7.41) but enrolled a population of light smokers and was judged to be at unclear risk of bias in two domains. Nine further trials did not detect significant effects. One of these tested CO feedback alone and CO combined with genetic susceptibility as two different interventions; none of the three possible comparisons detected significant effects. One trial used CO measurement, one used ultrasonography of carotid arteries and two tested for genetic markers. The four remaining trials used a combination of CO and spirometry feedback in different settings. AUTHORS' CONCLUSIONS: There is little evidence about the effects of most types of biomedical tests for risk assessment on smoking cessation. Of the fifteen included studies, only two detected a significant effect of the intervention. Spirometry combined with an interpretation of the results in terms of 'lung age' had a significant effect in a single good quality trial but the evidence is not optimal. A trial of carotid plaque screening using ultrasound also detected a significant effect, but a second larger study of a similar feedback mechanism did not detect evidence of an effect. Only two pairs of studies were similar enough in terms of recruitment, setting, and intervention to allow meta-analyses; neither of these found evidence of an effect. Mixed quality evidence does not support the hypothesis that other types of biomedical risk assessment increase smoking cessation in comparison to standard treatment. There is insufficient evidence with which to evaluate the hypothesis that multiple types of assessment are more effective than single forms of assessment.

EuroPhenome: a repository for high-throughput mouse phenotyping data.

The broad aim of biomedical science in the postgenomic era is to link genomic and phenotype information to allow deeper understanding of the processes leading from genomic changes to altered phenotype and disease. The EuroPhenome project (http://www.EuroPhenome.org) is a comprehensive resource for raw and annotated high-throughput phenotyping data arising from projects such as EUMODIC. EUMODIC is gathering data from the EMPReSSslim pipeline (http://www.empress.har.mrc.ac.uk/) which is performed on inbred mouse strains and knock-out lines arising from the EUCOMM project. The EuroPhenome interface allows the user to access the data via the phenotype or genotype. It also allows the user to access the data in a variety of ways, including graphical display, statistical analysis and access to the raw data via web services. The raw phenotyping data captured in EuroPhenome is annotated by an annotation pipeline which automatically identifies statistically different mutants from the appropriate baseline and assigns ontology terms for that specific test. Mutant phenotypes can be quickly identified using two EuroPhenome tools: PhenoMap, a graphical representation of statistically relevant phenotypes, and mining for a mutant using ontology terms. To assist with data definition and cross-database comparisons, phenotype data is annotated using combinations of terms from biological ontologies.

Biomedical and biological applications of scanning electron microscopy

This article summarizes the basic principles of scanning electron microscopy and the capabilities of the technique with different examples ofapplications in biomedical and biological research.

Biomedical risk assessment as an aid for smoking cessation.

BACKGROUND: A possible strategy for increasing smoking cessation rates could be to provide smokers who have contact with healthcare systems with feedback on the biomedical or potential future effects of smoking, e.g. measurement of exhaled carbon monoxide (CO), lung function, or genetic susceptibility to lung cancer. We reviewed systematically data on smoking cessation rates from controlled trials that used biomedical risk assessment and feedback. OBJECTIVES: To determine the efficacy of biomedical risk assessment provided in addition to various levels of counselling, as a contributing aid to smoking cessation. SEARCH STRATEGY: We systematically searched he Cochrane Collaboration Tobacco Addiction Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to 2004), and EMBASE (1980 to 2004). We combined methodological terms with terms related to smoking cessation counselling and biomedical measurements. SELECTION CRITERIA: Inclusion criteria were: a randomized controlled trial design; subjects participating in smoking cessation interventions; interventions based on a biomedical test to increase motivation to quit; control groups receiving all other components of intervention; an outcome of smoking cessation rate at least six months after the start of the intervention. DATA COLLECTION AND ANALYSIS: Two assessors independently conducted data extraction on each paper, with disagreements resolved by consensus. MAIN RESULTS: From 4049 retrieved references, we selected 170 for full text assessment. We retained eight trials for data extraction and analysis. One of the eight used CO alone and CO + Genetic Susceptibility as two different intervention groups, giving rise to three possible comparisons. Three of the trials isolated the effect of exhaled CO on smoking cessation rates resulting in the following odds ratios (ORs) and 95% confidence intervals (95% CI): 0.73 (0.38 to 1.39), 0.93 (0.62 to 1.41), and 1.18 (0.84 to 1.64). Combining CO measurement with genetic susceptibility gave an OR of 0.58 (0.29 to 1.19). Exhaled CO measurement and spirometry were used together in three trials, resulting in the following ORs (95% CI): 0.6 (0.25 to 1.46), 2.45 (0.73 to 8.25), and 3.50 (0.88 to 13.92). Spirometry results alone were used in one other trial with an OR of 1.21 (0.60 to 2.42).Two trials used other motivational feedback measures, with an OR of 0.80 (0.39 to 1.65) for genetic susceptibility to lung cancer alone, and 3.15 (1.06 to 9.31) for ultrasonography of carotid and femoral arteries performed in light smokers (average 10 to 12 cigarettes a day). AUTHORS' CONCLUSIONS: Due to the scarcity of evidence of sufficient quality, we can make no definitive statements about the effectiveness of biomedical risk assessment as an aid for smoking cessation. Current evidence of lower quality does not however support the hypothesis that biomedical risk assessment increases smoking cessation in comparison with standard treatment. Only two studies were similar enough in term of recruitment, setting, and intervention to allow pooling of data and meta-analysis.

Pathway databases and tools for their exploitation: benefits, current limitations and challenges

In past years, comprehensive representations of cell signalling pathways have been developed by manual curation from literature, which requires huge effort and would benefit from information stored in databases and from automatic retrieval and integration methods. Once a reconstruction of the network of interactions is achieved, analysis of its structural features and its dynamic behaviour can take place. Mathematical modelling techniques are used to simulate the complex behaviour of cell signalling networks, which ultimately sheds light on the mechanisms leading to complex diseases or helps in the identification of drug targets. A variety of databases containing information on cell signalling pathways have been developed in conjunction with methodologies to access and analyse the data. In principle, the scenario is prepared to make the most of this information for the analysis of the dynamics of signalling pathways. However, are the knowledge repositories of signalling pathways ready to realize the systems biology promise? In this article we aim to initiate this discussion and to provide some insights on this issue.

The EU-ADR Web Platform: delivering advanced pharmacovigilance tools

PURPOSE: Pharmacovigilance methods have advanced greatly during the last decades, making post-market drug assessment an essential drug evaluation component. These methods mainly rely on the use of spontaneous reporting systems and health information databases to collect expertise from huge amounts of real-world reports. The EU-ADR Web Platform was built to further facilitate accessing, monitoring and exploring these data, enabling an in-depth analysis of adverse drug reactions risks.METHODS: The EU-ADR Web Platform exploits the wealth of data collected within a large-scale European initiative, the EU-ADR project. Millions of electronic health records, provided by national health agencies, are mined for specific drug events, which are correlated with literature, protein and pathway data, resulting in a rich drug-event dataset. Next, advanced distributed computing methods are tailored to coordinate the execution of data-mining and statistical analysis tasks. This permits obtaining a ranked drug-event list, removing spurious entries and highlighting relationships with high risk potential.RESULTS: The EU-ADR Web Platform is an open workspace for the integrated analysis of pharmacovigilance datasets. Using this software, researchers can access a variety of tools provided by distinct partners in a single centralized environment. Besides performing standalone drug-event assessments, they can also control the pipeline for an improved batch analysis of custom datasets. Drug-event pairs can be substantiated and statistically analysed within the platform's innovative working environment.CONCLUSIONS: A pioneering workspace that helps in explaining the biological path of adverse drug reactions was developed within the EU-ADR project consortium. This tool, targeted at the pharmacovigilance community, is available online at https://bioinformatics.ua.pt/euadr/. Copyright © 2012 John Wiley & Sons, Ltd.

Sensitivity of Spring Phenology to Warming Across Temporal and Spatial Climate Gradients in Two Independent Databases

Disparate ecological datasets are often organized into databases post hoc and then analyzed and interpreted in ways that may diverge from the purposes of the original data collections. Few studies, however, have attempted to quantify how biases inherent in these data (for example, species richness, replication, climate) affect their suitability for addressing broad scientific questions, especially in under-represented systems (for example, deserts, tropical forests) and wild communities. Here, we quantitatively compare the sensitivity of species first flowering and leafing dates to spring warmth in two phenological databases from the Northern Hemisphere. One-PEP725-has high replication within and across sites, but has low species diversity and spans a limited climate gradient. The other-NECTAR-includes many more species and a wider range of climates, but has fewer sites and low replication of species across sites. PEP725, despite low species diversity and relatively low seasonality, accurately captures the magnitude and seasonality of warming responses at climatically similar NECTAR sites, with most species showing earlier phenological events in response to warming. In NECTAR, the prevalence of temperature responders significantly declines with increasing mean annual temperature, a pattern that cannot be detected across the limited climate gradient spanned by the PEP725 flowering and leafing data. Our results showcase broad areas of agreement between the two databases, despite significant differences in species richness and geographic coverage, while also noting areas where including data across broader climate gradients may provide added value. Such comparisons help to identify gaps in our observations and knowledge base that can be addressed by ongoing monitoring and research efforts. Resolving these issues will be critical for improving predictions in understudied and under-sampled systems outside of the temperature seasonal mid-latitudes.