Functional classification of CATH superfamilies: a domain-based approach for protein function annotation

Computational approaches that can predict protein functions are essential to bridge the widening function annotation gap especially since <1.0% of all proteins in UniProtKB have been experimentally characterised. We present a domain-based method for protein function classification and prediction of functional sites that exploits functional subclassification of CATH superfamilies. The superfamilies are subclassified into functional families (FunFams) using a hierarchical clustering algorithm supervised by a new classification method, FunFHMMer

CATH FunFHMMer web server: protein functional annotations using functional family assignments

The widening function annotation gap in protein databases and the increasing number and diversity of the proteins being sequenced presents new challenges to protein function prediction methods. Multidomain proteins complicate the protein sequence-structure-function relationship further as new combinations of domains can expand the functional repertoire, creating new proteins and functions. Here, we present the FunFHMMer web server, which provides Gene Ontology (GO) annotations for query protein sequences based on the functional classification of the domain-based CATH-Gene3D resource. Our server also provides valuable information for the prediction of functional sites. The predictive power of FunFHMMer has been validated on a set of 95 proteins where FunFHMMer performs better than BLAST, Pfam and CDD. Recent validation by an independent international competition ranks FunFHMMer as one of the top function prediction methods in predicting GO annotations for both the Biological Process and Molecular Function Ontology. The FunFHMMer web server is available at http://www.cathdb.info/search/by_funfhmmer

CATH: an expanded resource to predict protein function through structure and sequence

The latest version of the CATH-Gene3D protein structure classification database has recently been released (version 4.1, http://www.cathdb.info). The resource comprises over 300 000 domain structures and over 53 million protein domains classified into 2737 homologous superfamilies, doubling the number of predicted protein domains in the previous version. The daily-updated CATH-B, which contains our very latest domain assignment data, provides putative classifications for over 100 000 additional protein domains. This article describes developments to the CATH-Gene3D resource over the last two years since the publication in 2015, including: significant increases to our structural and sequence coverage; expansion of the functional families in CATH; building a support vector machine (SVM) to automatically assign domains to superfamilies; improved search facilities to return alignments of query sequences against multiple sequence alignments; the redesign of the web pages and download site

Gene3D: expanding the utility of domain assignments

Gene3D http://gene3d.biochem.ucl.ac.uk is a database of domain annotations of Ensembl and UniProtKB protein sequences. Domains are predicted using a library of profile HMMs representing 2737 CATH superfamilies. Gene3D has previously featured in the Database issue of NAR and here we report updates to the website and database. The current Gene3D (v14) release has expanded its domain assignments to ∼20 000 cellular genomes and over 43 million unique protein sequences, more than doubling the number of protein sequences since our last publication. Amongst other updates, we have improved our Functional Family annotation method. We have also improved the quality and coverage of our 3D homology modelling pipeline of predicted CATH domains. Additionally, the structural models have been expanded to include an extra model organism (Drosophila melanogaster). We also document a number of additional visualization tools in the Gene3D website

Permeability and acoustic velocity controlling factors determined from x-ray tomography images of carbonate rocks

Carbonate reservoir rocks exhibit a great variability in texture that directly impacts petrophysical parameters. Many exhibit bi- and multimodal pore networks, with pores ranging from less than 1 μm to several millimeters in diameter. Furthermore, many pore systems are too large to be captured by routine core analysis, and well logs average total porosity over different volumes. Consequently, prediction of carbonate properties from seismic data and log interpretation is still a challenge. In particular, amplitude versus offset classification systems developed for clastic rocks, which are dominated by connected, intergranular, unimodal pore networks, are not applicable to carbonate rocks. Pore geometrical parameters derived from digital image analysis (DIA) of thin sections were recently used to improve the coefficient of determination of velocity and permeability versus porosity. Although this substantially improved the coefficient of determination, no spatial information of the pore space was considered, because DIA parameters were obtained from two-dimensional analyses. Here, we propose a methodology to link local and global pore-space parameters, obtained from three-dimensional (3-D) images, to experimental physical properties of carbonate rocks to improve P-wave velocity and permeability predictions. Results show that applying a combination of porosity, microporosity, and 3-D geometrical parameters to P-wave velocity significantly improves the adjusted coefficient of determination from 0.490 to 0.962. A substantial improvement is also observed in permeability prediction (from 0.668 to 0.948). Both results can be interpreted to reflect a pore geometrical control and pore size control on P-wave velocity and permeability

Gene3D: Multi-domain annotations for protein sequence and comparative genome analysis

Gene3D (http://gene3d.biochem.ucl.ac.uk) is a database of protein domain structure annotations for protein sequences. Domains are predicted using a library of profile HMMs from 2738 CATH superfamilies. Gene3D assigns domain annotations to Ensembl and UniProt sequence sets including >6000 cellular genomes and >20 million unique protein sequences. This represents an increase of 45% in the number of protein sequences since our last publication. Thanks to improvements in the underlying data and pipeline, we see large increases in the domain coverage of sequences. We have expanded this coverage by integrating Pfam and SUPERFAMILY domain annotations, and we now resolve domain overlaps to provide highly comprehensive composite multi-domain architectures. To make these data more accessible for comparative genome analyses, we have developed novel search algorithms for searching genomes to identify related multi-domain architectures. In addition to providing domain family annotations, we have now developed a pipeline for 3D homology modelling of domains in Gene3D. This has been applied to the human genome and will be rolled out to other major organisms over the next year

Recruitment of ethnic minority patients to a cardiac rehabilitation trial: The Birmingham Rehabilitation Uptake Maximisation (BRUM) study [ISRCTN72884263]

Background: Concerns have been raised about low participation rates of people from minority ethnic groups in clinical trials. However, the evidence is unclear as many studies do not report the ethnicity of participants and there is insufficient information about the reasons for ineligibility by ethnic group. Where there are data, there remains the key question as to whether ethnic minorities more likely to be ineligible (e.g. due to language) or decline to participate. We have addressed these questions in relation to the Birmingham Rehabilitation Uptake Maximisation (BRUM) study, a randomized controlled trial (RCT) comparing a home-based with a hospital-based cardiac rehabilitation programme in a multi-ethnic population in the UK. Methods: Analysis of the ethnicity, age and sex of presenting and recruited subjects for a trial of cardiac rehabilitation in the West-Midlands, UK. Participants: 1997 patients presenting post-myocardial infarction, percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery. Data collected: exclusion rates, reasons for exclusion and reasons for declining to participate in the trial by ethnic group. Results: Significantly more patients of South Asian ethnicity were excluded (52% of 'South Asian' v 36% 'White European' and 36% 'Other', p < 0.001). This difference in eligibility was primarily due to exclusion on the basis of language (i.e. the inability to speak English or Punjabi). Of those eligible, similar proportions were recruited from the different ethnic groups (white, South Asian and other). There was a marked difference in eligibility between people of Indian, Pakistani or Bangladeshi origin

Incidence and predictors of onboard injuries among Sri Lankan flight attendants

<p>Abstract</p> <p>Background</p> <p>Occupational injuries among flight attendants have not been given appropriate attention in Sri Lanka. The purpose of this study was to estimate the incidence of onboard injury among Sri Lankan flight attendants and to describe the determinants of onboard injury.</p> <p>Methods</p> <p>A descriptive cross-sectional study was carried out among Sri Lankan flight attendants. All flight attendants undergoing their annual health and first aid training were invited to participate. Flight attendants who flew continuously for a six-month period prior to data collection were included in the study sample. Recall history of injuries for a period of six months was recorded.</p> <p>Results</p> <p>The study sample consisted of 98 (30.4%) male and 224 (69.6%) female flight attendants. The mean age of the study sample was 31 years (SD = 8) and the average duration of service was 10 years (SD = 7). A total of 100 onboard falls, slips or trips in the previous six months were reported by 52 (16.1%) respondents. Of the total sample, 128 (39.8%) cabin crew members reported an injury in the six months preceding the study. This represents a total injury incidence of 795 per 1000 person per year. The leading causes of injury was pulling, pushing or lifting (60.2%). The commonest type of injuries were strains and sprains (52.3%). Turbulence related injuries were reported by 38 (29.7%) flight attendants. The upper limbs (44.5%) and the back (32%) were the commonest sites affected. After controlling for other factors, female flight attendants had 2.9 times higher risk (95% CI 1.2–7.2) of sustaining and injury than males. Irrespective of sex, body weight less than 56 kilograms (OR 2.9, 95% CI 1.4–5.8) and less than seven years of on board experience (OR 10.5, 95% CI 3.6–31.0) were associated with higher risk of injury.</p> <p>Conclusion</p> <p>Work related injury is a major occupational hazard to flight attendants. Appropriate preventive strategies are required to minimize them.</p

Attention deficit hyperactivity symptoms predict problematic mobile phone use

Attention-deficit-hyperactivity disorder (ADHD) is the most commonly diagnosed childhood disorder characterised by inattention, hyperactivity/impulsivity, or both. Some of the key traits of ADHD have previously been linked to addictive and problematic behaviours. The aim of the present study was to examine the relationship between problematic mobile phone use, smartphone addiction risk and ADHD symptoms in an adult population. A sample of 273 healthy adult volunteers completed the Adult ADHD Self-Report Scale (ASRS), the Mobile Phone Problem Usage Scale (MPPUS), and the Smartphone Addiction Scale (SAS). A significant positive correlation was found between the ASRS and both scales. More specifically, inattention symptoms and age predicted smartphone addiction risk and problematic mobile phone use. Our results suggest that there is a positive relationship between ADHD traits and problematic mobile phone use. In particular, younger adults with higher level of inattention symptoms could be at higher risk of developing smartphone addiction. The implication of our findings for theoretical frameworks of problematic mobile phone use and clinical practice are discussed