Analyzing inconsistency toward enhancing integration of biological molecular databases

The rapid growth of biological databases not only provides biologists with abundant data but also presents a big challenge in relation to the analysis of data. Many data analysis approaches such as data mining, information retrieval and machine learning have been used to extract frequent patterns from diverse biological databases. However, the discrepancies, due to the differences in the structure of databases and their terminologies, result in a significant lack of interoperability. Although ontology-based approaches have been used to integrate biological databases, the inconsistent analysis of biological databases has been greatly disregarded. This paper presents a method by which to measure the degree of inconsistency between biological databases. It not only presents a guideline for correct and efficient database integration, but also exposes high quality data for data mining and knowledge discovery.

A provisional database for the silicon content of foods in the United Kingdom

Si may play an important role in bone formation and connective tissue metabolism. Although biological interest in this element has recently increased, limited literature exists on the Si content of foods. To further our knowledge and understanding of the relationship between dietary Si and human health, a reliable food composition database, relevant for the UK population, is required. A total of 207 foods and beverages, commonly consumed in the UK, were analysed for Si content. Composite samples were analysed using inductively coupled plasma–optical emission spectrometry following microwave-assisted digestion with nitric acid and H2O2. The highest concentrations of Si were found in cereals and cereal products, especially less refined cereals and oat-based products. Fruit and vegetables were highly variable sources of Si with substantial amounts present in Kenyan beans, French beans, runner beans, spinach, dried fruit, bananas and red lentils, but undetectable amounts in tomatoes, oranges and onions. Of the beverages, beer, a macerated whole-grain cereal product, contained the greatest level of Si, whilst drinking water was a variable source with some mineral waters relatively high in Si. The present study provides a provisional database for the Si content of UK foods, which will allow the estimation of dietary intakes of Si in the UK population and investigation into the role of dietary Si in human health.

Stakeholder satisfaction with the Australian Rheumatology Association Database (ARAD)

Background: The Australian Rheumatology Association Database (ARAD) is a voluntary national registry for monitoring the long-term benefits and safety of biological disease-modifying anti-rheumatic drugs (bDMARDs) for inflammatory arthritis. Both rheumatologists and patients contribute data to the ARAD.

Objective: To evaluate the satisfaction of patients and rheumatologists with the ARAD.

Methods: Cross-sectional surveys were distributed to a random sample of 100 community-dwelling ARAD patients in 2007 and to rheumatologists attending the 2007 AustralianRheumatologyAssociation (ARA) annual scientific meeting.

Survey questions included items about the usefulness of the ARAD, workload for participants, frequency of questionnaires, and experience of contact with ARAD staff.

Results: A total of 92.5% of patients perceived the ARAD as very important (scoring 9-10 on a numeric rating scale). Patients reported minimal difficulty in completing questionnaires, and 95.0% indicated that a 6-month interval between questionnaires was reasonable. Of responding rheumatologists, 32.3%, 62.1%, and 53.8% indicated that the ARAD was very important (scoring 8-10) with respect to clinical information, research, and the profession, respectively, while 68% of those participating in the ARAD reported that the workload required to enroll patients was manageable and 30% found it difficult or onerous.

Conclusion: Key stakeholders in the ARAD view it as an important resource and are satisfied with its operations. Efforts will be directed towards assisting those rheumatologists who find the associated workload difficult and to improving the perceived clinical value of information available from the ARAD.

Ankylosing spondylitis patients commencing biologic therapy have high baseline levels of comorbidity: a report from the Australian Rheumatology Association Database

Aims: To compare the baseline characteristics of a population-based cohort of patients with ankylosing spondylitis (AS) commencing biological therapy to the reported characteristics of bDMARD randomised controlled trials (RCTs) participants.
Methods: Descriptive analysis of AS participants in the Australian Rheumatology Association Database (ARAD) who were commencing bDMARD therapy.
Results: Up to December 2008, 389 patients with AS were enrolled in ARAD. 354 (91.0%) had taken bDMARDs at some time, and 198 (55.9%) completed their entry questionnaire prior to or within 6 months of commencing bDMARDs. 131 (66.1%) had at least one comorbid condition, and 24 (6.8%) had a previous malignancy (15 nonmelanoma skin, 4 melanoma, 2 prostate, 1 breast, cervix, and bowel). Compared with RCT participants, ARAD participants were older, had longer disease duration and higher baseline disease activity.
Conclusions: AS patients commencing bDMARDs in routine care are significantly different to RCT participants and have significant baseline comorbidities.

Satellyptus: analysis and database of microsatellites from ESTs of Eucalyptus

The main goal of our research was to search for SSRs in the Eucalyptus EST FORESTs database (using a software for mining SSR-motifs). With this objective, we created a database for cataloging Eucalyptus EST-derived SSRs, and developed a bioinformatics tool, named Satellyptus, for finding and analyzing microsatellites in the Eucalyptus EST database. The search for microsatellites in the FORESTs database containing 71,115 Eucalyptus EST sequences (52.09 Mb) revealed 20,530 SSRs in 15,621 ESTs. The SSR abundance detected on the Eucalyptus ESTs database (29% or one microsatellite every four sequences) is considered very high for plants. Amongst the categories of SSR motifs, the dimeric (37%) and trimeric ones (33%) predominated. The AG/CT motif was the most frequent (35.15%) followed by the trimeric CCG/CGG (12.81%). From a random sample of 1,217 sequences, 343 microsatellites in 265 SSR-containing sequences were identified. Approximately 48% of these ESTs containing microsatellites were homologous to proteins with known biological function. Most of the microsatellites detected in Eucalyptus ESTs were positioned at either the 5 or 3 end. Our next priority involves the design of flanking primers for codominant SSR loci, which could lead to the development of a set of microsatellite-based markers suitable for marker-assisted Eucalyptus breeding programs.

HTRIdb: an open-access database for experimentally verified human transcriptional regulation interactions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Development of a natural products database from the biodiversity of Brazil

We describe herein the design and development of an innovative tool called the NuBBE database (NuBBEDB), a new Web-based database, which incorporates several classes of secondary metabolites and derivatives from the biodiversity of Brazil. This natural product database incorporates botanical, chemical, pharmacological, and toxicological compound information. The NuBBEDB provides specialized information to the worldwide scientific community and can serve as a useful tool for studies on the multidisciplinary interfaces related to chemistry and biology, including virtual screening, dereplication, metabolomics, and medicinal chemistry. The NuBBEDB site is at http://nubbe.iq.unesp.br/nubbeDB.html. © 2013 The American Chemical Society and American Society of Pharmacognosy.

Conventional versus biological therapy for prevention of postoperative endoscopic recurrence in patients with Crohn's disease: an international, multicenter, and observational study

Postoperative endoscopic recurrence (PER) occurs in nearly 80% of patients 1 year after ileocecal resection in patients with Crohn's disease (CD). Biological agents were more effective in reducing the rates of PER in comparison with conventional therapy, in prospective trials. The aim of this study was to compare the PER rates of biological versus conventional therapy after ileocecal resections in patients with CD in real-world practice. The MULTIPER (Multicenter International Postoperative Endoscopic Recurrence) database is a retrospective analysis of PER rates in CD patients after ileocecal resection, from 7 referral centers in 3 different countries. All consecutive patients who underwent ileocecal resections between 2008 and 2012 and in whom colonoscopies had been performed up to 12 months after surgery, were included. Recurrence was defined as Rutgeerts' score ≥i2. The patients were allocated to either biological or conventional therapy after surgery, and PER rates were compared between the groups. Initially, 231 patients were evaluated, and 63 were excluded. Of the 168 patients in the database, 96 received anti-tumor necrosis factor agents and 72 were treated with conventional therapy after resection. The groups were comparable regarding age, gender, and perianal disease. There was longer disease duration, more previous resections, and more open surgical procedures in patients on biologicals postoperatively. PER was identified in 25/96 (26%) patients on biological therapy and in 24/72 (33.3%) patients on conventional therapy (P=0.310). In this retrospective observational analysis from an international database, no difference was observed between biological and conventional therapy in preventing PER after ileocecal resections in CD patients.

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia, Part 1: Update 2012 on the acute treatment of schizophrenia and the management of treatment resistance

These updated guidelines are based on a first edition of the World Federation of Societies of Biological Psychiatry Guidelines for Biological Treatment of Schizophrenia published in 2005. For this 2012 revision, all available publications pertaining to the biological treatment of schizophrenia were reviewed systematically to allow for an evidence-based update. These guidelines provide evidence-based practice recommendations that are clinically and scientifically meaningful and these guidelines are intended to be used by all physicians diagnosing and treating people suffering from schizophrenia. Based on the first version of these guidelines, a systematic review of the MEDLINE/PUBMED database and the Cochrane Library, in addition to data extraction from national treatment guidelines, has been performed for this update. The identified literature was evaluated with respect to the strength of evidence for its efficacy and then categorised into six levels of evidence (A-F; Bandelow et al. 2008b, World J Biol Psychiatry 9: 242). This first part of the updated guidelines covers the general descriptions of antipsychotics and their side effects, the biological treatment of acute schizophrenia and the management of treatment-resistant schizophrenia.

Uric acid biorhythm, a feature of long-term variation in a clinical laboratory database

Background: The biorhythm of serum uric acid was evaluated in a large sample of a clinical laboratory database by spectral analysis and the influence of the gender and age on uric acid variability. Methods: Serum uric acid values were extracted from a large database of a clinical laboratory from May 2000 to August 2006. Outlier values were excluded from the analysis and the remaining data (n = 73,925) were grouped by gender and age ranges. Rhythm components were obtained by the Lomb Scargle method and Cosinor analysis. Results: Serum uric acid was higher in men than in women older than 13 years (p<0.05). Compared with 0-12 year group, uric acid increased in men but not in women older than 13 years (p<0.05). Circannual (12 months) and transyear (17 months) rhythm components were detected, but they were significant only in adult individuals (>26 years, p<0.05). Cosinor analysis showed that midline estimating statistic of rhythm (MESOR) values were higher in men (range: 353-368 mu mol/L) than in women (range: 240-278 mu mol/L; p<0.05), independent of the age and rhythm component. The extent of predictable change within a cycle, approximated by the double amplitude, represented up to 20% of the corresponding MESOR. Conclusions: Serum uric acid biorhythm is dependent on gender and age and it may have relevant influence on preanalytical variability of clinical laboratory results.

Database of diazotrophs in global ocean: abundances, biomass and nitrogen fixation rates

[EN] Marine N2 fixing microorganisms, termed diazotrophs, are a key functional group in marine pelagic ecosystems. The biological fixation of dinitrogen (N2) to bioavailable nitrogen provides an important new source of nitrogen for pelagic marine ecosystems 5 and influences primary productivity and organic matter export to the deep ocean. As one of a series of efforts to collect biomass and rates specific to different phytoplankton functional groups, we have constructed a database on diazotrophic organisms in the global pelagic upper ocean by compiling about 12 000 direct field measurements of cyanobacterial diazotroph abundances (based on microscopic cell counts or qPCR 10 assays targeting the nifH genes) and N2 fixation rates. Biomass conversion factors are estimated based on cell sizes to convert  abundance data to diazotrophic biomass. The database is limited spatially, lacking large regions of the ocean especially in the Indian Ocean. The data are approximately log-normal distributed, and large variances exist in most sub-databases with non-zero values differing 5 to 8 orders of magnitude. 15 Lower mean N2 fixation rate was found in the North Atlantic Ocean than the Pacific Ocean. Reporting the geometric mean and the range of one geometric standard error below and above the geometric mean, the pelagic N2 fixation rate in the global ocean is estimated to be 62 (53–73) TgNyr−1 and the pelagic diazotrophic biomass in the global ocean is estimated to be 4.7 (2.3–9.6) TgC from cell counts and to 89 (40–20 200) TgC from nifH-based abundances. Uncertainties related to biomass conversion factors can change the estimate of geometric mean pelagic diazotrophic biomass in the global ocean by about ±70 %. This evolving database can be used to study spatial and temporal distributions and variations of marine N2 fixation, to validate geochemical estimates and to parameterize and validate biogeochemical models. The database is 25 stored in PANGAEA (http://doi.pangaea.de/10.1594/PANGAEA.774851).

Identification of stock units of Mullus barbatus (Linnaeus, 1758) in the Italian seas: development of genomic 2b-RAD markers and biological variation analysis.

This thesis is settled within the STOCKMAPPING project, which represents one of the studies that were developed in the framework of RITMARE Flagship project. The main goals of STOCKMAPPING were the creation of a genomic mapping for stocks of demersal target species and the assembling of a database of population genomic, in order to identify stocks and stocks boundaries. The thesis focuses on three main objectives representing the core for the initial assessment of the methodologies and structure that would be applied to the entire STOCKMAPPING project: individuation of an analytical design to identify and locate stocks and stocks boundaries of Mullus barbatus, application of a multidisciplinary approach to validate biological methods and an initial assessment and improvement for the genotyping by sequencing technique utilized (2b-RAD). The first step is the individuation of an analytical design that has to take in to account the biological characteristics of red mullet and being representative for STOCKMAPPING commitments. In this framework a reduction and selection steps was needed due to budget reduction. Sampling areas were ranked according the individuation of four priorities. To guarantee a multidisciplinary approach the biological data associated to the collected samples were used to investigate differences between sampling areas and GSAs. Genomic techniques were applied to red mullet for the first time so an initial assessment of molecular protocols for DNA extraction and 2b-RAD processing were needed. At the end 192 good quality DNAs have been extracted and eight samples have been processed with 2b-RAD. Utilizing the software Stacks for sequences analyses a great number of SNPs markers among the eight samples have been identified. Several tests have been performed changing the main parameter of the Stacks pipeline in order to identify the most explicative and functional sets of parameters.

Lead discovery, chemistry optimization, and biological evaluation studies of novel biamide derivatives as CB2 receptor inverse agonists and osteoclast inhibitors

N,N'-((4-(Dimethylamino)phenyl)methylene)bis(2-phenylacetamide) was discovered by using 3D pharmacophore database searches and was biologically confirmed as a new class of CB(2) inverse agonists. Subsequently, 52 derivatives were designed and synthesized through lead chemistry optimization by modifying the rings A-C and the core structure in further SAR studies. Five compounds were developed and also confirmed as CB(2) inverse agonists with the highest CB(2) binding affinity (CB(2)K(i) of 22-85 nM, EC(50) of 4-28 nM) and best selectivity (CB(1)/CB(2) of 235- to 909-fold). Furthermore, osteoclastogenesis bioassay indicated that PAM compounds showed great inhibition of osteoclast formation. Especially, compound 26 showed 72% inhibition activity even at the low concentration of 0.1 μM. The cytotoxicity assay suggested that the inhibition of PAM compounds on osteoclastogenesis did not result from its cytotoxicity. Therefore, these PAM derivatives could be used as potential leads for the development of a new type of antiosteoporosis agent.