EnzyMiner: automatic identification of protein level mutations and their impact on target enzymes from PubMed abstracts

BACKGROUND: A better understanding of the mechanisms of an enzyme's functionality and stability, as well as knowledge and impact of mutations is crucial for researchers working with enzymes. Though, several of the enzymes' databases are currently available, scientific literature still remains at large for up-to-date source of learning the effects of a mutation on an enzyme. However, going through vast amounts of scientific documents to extract the information on desired mutation has always been a time consuming process. In this paper, therefore, we describe an unique method, termed as EnzyMiner, which automatically identifies the PubMed abstracts that contain information on the impact of a protein level mutation on the stability and/or the activity of a given enzyme. RESULTS: We present an automated system which identifies the abstracts that contain an amino-acid-level mutation and then classifies them according to the mutation's effect on the enzyme. In the case of mutation identification, MuGeX, an automated mutation-gene extraction system has an accuracy of 93.1% with a 91.5 F-measure. For impact analysis, document classification is performed to identify the abstracts that contain a change in enzyme's stability or activity resulting from the mutation. The system was trained on lipases and tested on amylases with an accuracy of 85%. CONCLUSION: EnzyMiner identifies the abstracts that contain a protein mutation for a given enzyme and checks whether the abstract is related to a disease with the help of information extraction and machine learning techniques. For disease related abstracts, the mutation list and direct links to the abstracts are retrieved from the system and displayed on the Web. For those abstracts that are related to non-diseases, in addition to having the mutation list, the abstracts are also categorized into two groups. These two groups determine whether the mutation has an effect on the enzyme's stability or functionality followed by displaying these on the web

Recognition of Clostridium difficile PCR-ribotypes 001, 027 and 126/078 using an extended MALDI-TOF MS system

During the last decade, Clostridium difficile infection (CDI) increased markedly inside as well as outside of hospitals. In association with the occurrence of new hypervirulent C. difficile strains, CDI became more important. Until now typing of C. difficile strains has been enabled by PCR-ribotyping. However, this method is restricted to specialized laboratories combined with high maintenance cost. Therefore, we tested MALDI-TOF mass spectrometry for typing of C. difficile to provide a fast method for surveillance of CDI. Using a standard set of 25 different C. difficile PCR ribotypes a database was made by different mass spectra recorded in the SARAMIS™ software (AnagnosTec, Zossen, Germany). The database was validated with 355 C. difficile strains belonging to 29 different PCR ribotypes collected prospectively from all submitted feces samples in 2009. The most frequent PCR ribotypes were type 001 (70%), 027 (4.8%) and 078/126 (4.7%). All three types were recognized by MALDI-TOF MS. We conclude that an extended MALDI-TOF system was capable to recognize specific markers for ribotypes 001, 027 and 078/126 allowing an effective identification of these strains

Vitamin D deficiency is an independent predictor of mortality in patients with chronic heart failure

Purpose: Low 25-hydroxyvitamin D (25[OH]D) concentrations have been associated with adverse outcomes in selected populations with established chronic heart failure (CHF). However, it remains unclear whether 25[OH]D deficiency is associated with mortality and hospitalisation in unselected patients receiving contemporary medical and device therapy for CHF. Methods: We prospectively examined the prevalence and correlates of 25[OH]D deficiency in 1802 ambulatory patients with CHF due to left ventricular systolic dysfunction (left ventricular ejection fraction ≤ 45%) attending heart failure clinics in the north of England. Results: 73% of patients were deficient in 25[OH]D (< 50 nmol/L). 25[OH]D deficiency was associated with male sex, diabetes, lower serum sodium, higher heart rate, and greater diuretic requirement. During a mean follow-up period of 4 years, each 2.72-fold increment in 25[OH]D concentration (for example from 32 to 87 nmol/L) is associated with 14% lower all-cause mortality (95% confidence interval (CI) 1, 26%; p = 0.04), after accounting for potential confounding factors. Conclusions: Low 25-hydroxyvitamin D deficiency is associated with increased mortality in patients with chronic heart failure due to left ventricular systolic dysfunction. Whether vitamin D supplementation will improve outcomes is, as yet, unproven

Personal and Financial Risk Typologies Among Women Who Engage in Sex Work in Mongolia: A Latent Class Analysis

Women engaged in sex work bear a disproportionate burden of HIV infection worldwide, particularly in low- to middle-income countries. Stakeholders interested in promoting prevention and treatment programs are challenged to efficiently and effectively target heterogeneous groups of women. This problem is particularly difficult because it is nearly impossible to know how those groups are composed a priori. Although grouping based on individual variables (e.g., age or place of solicitation) can describe a sample of women engaged in sex work, selecting these variables requires a strong intuitive understanding of the population.Furthermore, this approach is difficult to quantify and has the potential to reinforce preconceived notions, rather than generate new information. We aimed to investigate groupings of women engaged in sex work. The data were collected from a sample of 204 women who were referred to an HIV prevention intervention in Ulaanbaatar, Mongolia. Latent class analysis was used to create subgroups of women engaged in sex work, based on personal and financial risk factors.This analysis found three latent classes, representing unique response pattern profiles of personal and financial risk. The current study approached typology research in a novel, more empirical way and provided a description of different subgroups, which may respond differently to HIV risk interventions

Substrate Induced Strain Field in FeRh Epilayers Grown on Single Crystal MgO (001) Substrates

Equi-atomic FeRh is highly unusual in that it undergoes a first order meta-magnetic phase transition from an antiferromagnet to a ferromagnet above room temperature (Tr ≈ 370 K). This behavior opens new possibilities for creating multifunctional magnetic and spintronic devices which can utilise both thermal and applied field energy to change state and functionalise composites. A key requirement in realising multifunctional devices is the need to understand and control the properties of FeRh in the extreme thin film limit (tFeRh < 10 nm) where interfaces are crucial. Here we determine the properties of FeRh films in the thickness range 2.5–10 nm grown directly on MgO substrates. Our magnetometry and structural measurements show that a perpendicular strain field exists in these thin films which results in an increase in the phase transition temperature as thickness is reduced. Modelling using a spin dynamics approach supports the experimental observations demonstrating the critical role of the atomic layers close to the MgO interface

Annotation of protein residues based on a literature analysis: cross-validation against UniProtKb

<p>Abstract</p> <p>Background</p> <p>A protein annotation database, such as the Universal Protein Resource knowledge base (UniProtKb), is a valuable resource for the validation and interpretation of predicted 3D structure patterns in proteins. Existing studies have focussed on point mutation extraction methods from biomedical literature which can be used to support the time consuming work of manual database curation. However, these methods were limited to point mutation extraction and do not extract features for the annotation of proteins at the residue level.</p> <p>Results</p> <p>This work introduces a system that identifies protein residues in MEDLINE abstracts and annotates them with features extracted from the context written in the surrounding text. MEDLINE abstract texts have been processed to identify protein mentions in combination with taxonomic species and protein residues (F1-measure 0.52). The identified protein-species-residue triplets have been validated and benchmarked against reference data resources (UniProtKb, average F1-measure of 0.54). Then, contextual features were extracted through shallow and deep parsing and the features have been classified into predefined categories (F1-measure ranges from 0.15 to 0.67). Furthermore, the feature sets have been aligned with annotation types in UniProtKb to assess the relevance of the annotations for ongoing curation projects. Altogether, the annotations have been assessed automatically and manually against reference data resources.</p> <p>Conclusion</p> <p>This work proposes a solution for the automatic extraction of functional annotation for protein residues from biomedical articles. The presented approach is an extension to other existing systems in that a wider range of residue entities are considered and that features of residues are extracted as annotations.</p

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Expansion of Canopy-Forming Willows Over the Twentieth Century on Herschel Island, Yukon Territory, Canada

Canopy-forming shrubs are reported to be increasing at sites around the circumpolar Arctic. Our results indicate expansion in canopy cover and height of willows on Herschel Island located at 70° north on the western Arctic coast of the Yukon Territory. We examined historic photographs, repeated vegetation surveys, and conducted monitoring of long-term plots and found evidence of increases of each of the dominant canopy-forming willow species (Salix richardsonii, Salix glauca and Salix pulchra), during the twentieth century. A simple model of patch initiation indicates that the majority of willow patches for each of these species became established between 1910 and 1960, with stem ages and maximum growth rates indicating that some patches could have established as late as the 1980s. Collectively, these results suggest that willow species are increasing in canopy cover and height on Herschel Island. We did not find evidence that expansion of willow patches is currently limited by herbivory, disease, or growing conditions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13280-011-0168-y) contains supplementary material, which is available to authorized users

IS element IS16 as a molecular screening tool to identify hospital-associated strains of Enterococcus faecium

<p>Abstract</p> <p>Background</p> <p>Hospital strains of <it>Enterococcus faecium </it>could be characterized and typed by various molecular methods (MLST, AFLP, MLVA) and allocated to a distinct clonal complex known as MLST CC17. However, these techniques are laborious, time-consuming and cost-intensive. Our aim was to identify hospital <it>E. faecium </it>strains and differentiate them from colonizing and animal variants by a simple, inexpensive and reliable PCR-based screening assay. We describe here performance and predictive value of a single PCR detecting the insertion element, IS<it>16</it>, to identify hospital <it>E. faecium </it>isolates within a collection of 260 strains of hospital, animal and human commensal origins.</p> <p>Methods</p> <p>Specific primers were selected amplifying a 547-bp fragment of IS<it>16</it>. Presence of IS<it>16 </it>was determined by PCR screenings among the 260 <it>E. faecium </it>isolates. Distribution of IS<it>16 </it>was compared with a prevalence of commonly used markers for hospital strains, <it>esp </it>and <it>hyl</it>_<it>Efm</it>. All isolates were typed by MLST and partly by PFGE. Location of IS<it>16 </it>was analysed by Southern hybridization of plasmid and chromosomal DNA.</p> <p>Results</p> <p>IS<it>16 </it>was exclusively distributed only among 155 invasive strains belonging to the clonal complex of hospital-associated strains ("CC17"; 28 MLST types) and various vancomycin resistance genotypes (<it>van</it>A/B/negative). The five invasive IS<it>16</it>-negative strains did not belong to the clonal complex of hospital-associated strains (CC17). IS<it>16 </it>was absent in all but three isolates from 100 livestock, food-associated and human commensal strains ("non-CC17"; 64 MLST types). The three IS<it>16</it>-positive human commensal isolates revealed MLST types belonging to the clonal complex of hospital-associated strains (CC17). The values predicting a hospital-associated strain ("CC17") deduced from presence and absence of IS<it>16 </it>was 100% and thus superior to screening for the presence of <it>esp </it>(66%) and/or <it>hyl</it>_{<it>Efm </it>}(46%). Southern hybridizations revealed chromosomal as well as plasmid localization of IS<it>16</it>.</p> <p>Conclusions</p> <p>This simple screening assay for insertion element IS<it>16 </it>is capable of differentiating hospital-associated from human commensal, livestock- and food-associated <it>E. faecium </it>strains and thus allows predicting the epidemic strengths or supposed pathogenic potential of a given <it>E. faecium </it>isolate identified within the nosocomial setting.</p