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1.  Is the Prevalence of Metabolic Syndrome and Metabolic Abnormalities Increased in Early Schizophrenia? A Comparative Meta-Analysis of First Episode, Untreated and Treated Patients 
Schizophrenia Bulletin  2012;39(2):295-305.
We aimed to discover whether metabolic complications of schizophrenia (SZ) are present in first episode (FE) and unmedicated (UM) patients, in comparison with patients established on antipsychotic medication (AP).
Method:
A systematic search, critical appraisal, and meta-analysis were conducted of studies to December 2011 using Medline, PsycINFO, Embase and experts. Twenty-six studies examined FE SZ patients (n = 2548) and 19 included UM SZ patients (n = 1325). For comparison we identified 78 publications involving 24 892 medicated patients who had chronic SZ already established on AP.
Results:
In UM, the overall rate of metabolic syndrome (MetS) was 9.8% using any standardized criteria. Diabetes was found in only 2.1% and hyperglycaemia (>100mg/dl) in 6.4%. In FE, the overall MetS rate was 9.9%, diabetes was found in only 1.2%, and hyperglycaemia in 8.7%. In UM and FE, the rates of overweight were 26.6%, 22%; hypertriglyceridemia 16.9%, 19.6%; low HDL 20.4%, 21.9%; high blood pressure 24.3%, 30.4%; smoking 40.2%, 46.8%, respectively. In both groups all metabolic components and risk factors were significantly less common in early SZ than in those already established on AP. Waist size, blood pressure and smoking were significantly lower in UM compared with FE.
Conclusion:
There is a significantly lower cardiovascular risk in early SZ than in chronic SZ. Both diabetes and pre-diabetes appear uncommon in the early stages, especially in UM. However, smoking does appear to be elevated early after diagnosis. Clinicians should focus on preventing initial cardiometabolic risk because subsequent reduction in this risk is more difficult to achieve, either through behavioral or pharmacologic interventions.
doi:10.1093/schbul/sbs082
PMCID: PMC3576152  PMID: 22927670
cardiovascular risk; diabetes; lipids; glucose; waist; obesity
2.  Prevalence of Metabolic Syndrome and Metabolic Abnormalities in Schizophrenia and Related Disorders—A Systematic Review and Meta-Analysis 
Schizophrenia Bulletin  2011;39(2):306-318.
Individuals with schizophrenia have high levels of medical comorbidity and cardiovascular risk factors. The presence of 3 or more specific factors is indicative of metabolic syndrome, which is a significant influence upon future morbidity and mortality. We aimed to clarify the prevalence and predictors of metabolic syndrome (MetS) in adults with schizophrenia and related disorders, accounting for subgroup differences. A PRISMA systematic search, appraisal, and meta-analysis were conducted of 126 analyses in 77 publications (n = 25 692). The overall rate of MetS was 32.5% (95% CI = 30.1%–35.0%), and there were only minor differences according to the different definitions of MetS, treatment setting (inpatient vs outpatient), by country of origin and no appreciable difference between males and females. Older age had a modest influence on the rate of MetS (adjusted R 2 = .20; P < .0001), but the strongest influence was of illness duration (adjusted R 2 = .35; P < .0001). At a study level, waist size was most useful in predicting high rate of MetS with a sensitivity of 79.4% and a specificity of 78.8%. Sensitivity and specificity of high blood pressure, high triglycerides, high glucose and low high-density lipoprotein, and age (>38 y) are shown in supplementary appendix 2 online. Regarding prescribed antipsychotic medication, highest rates were seen in those prescribed clozapine (51.9%) and lowest rates of MetS in those who were unmedicated (20.2%). Present findings strongly support the notion that patients with schizophrenia should be considered a high-risk group. Patients with schizophrenia should receive regular monitoring and adequate treatment of cardio-metabolic risk factors.
doi:10.1093/schbul/sbr148
PMCID: PMC3576174  PMID: 22207632
metabolic syndrome; cardiovascular risk; diabetes; lipids; glucose; schizophrenia; waist; obesity; smoking
3.  InterProScan 5: genome-scale protein function classification 
Bioinformatics  2014;30(9):1236-1240.
Motivation: Robust large-scale sequence analysis is a major challenge in modern genomic science, where biologists are frequently trying to characterize many millions of sequences. Here, we describe a new Java-based architecture for the widely used protein function prediction software package InterProScan. Developments include improvements and additions to the outputs of the software and the complete reimplementation of the software framework, resulting in a flexible and stable system that is able to use both multiprocessor machines and/or conventional clusters to achieve scalable distributed data analysis. InterProScan is freely available for download from the EMBl-EBI FTP site and the open source code is hosted at Google Code.
Availability and implementation: InterProScan is distributed via FTP at ftp://ftp.ebi.ac.uk/pub/software/unix/iprscan/5/ and the source code is available from http://code.google.com/p/interproscan/.
Contact: http://www.ebi.ac.uk/support or interhelp@ebi.ac.uk or mitchell@ebi.ac.uk
doi:10.1093/bioinformatics/btu031
PMCID: PMC3998142  PMID: 24451626
4.  A Systematic Review of Randomized, Double-Blind, Placebo-Controlled Trials Examining the Clinical Efficacy of Vitamin D in Multiple Sclerosis 
Neuroepidemiology  2012;40(3):147-153.
Background
An association between multiple sclerosis (MS) prevalence as well as MS mortality and vitamin D nutrition has led to the hypothesis that high levels of vitamin D could be beneficial for MS. The purpose of this systematic review is to establish whether there is evidence for or against vitamin D in the treatment of MS.
Methods
Systematic literature searches were performed to locate randomized, placebo-controlled, double-blind trials measuring the clinical effect of vitamin D on MS in human participants. Data were extracted in a standardized manner and methodological quality was assessed by the Jadad score.
Results
Five trials were located meeting the selection criteria. Of the five trials, four showed no effect of vitamin D on any outcome, and one showed a significant effect, namely upon reduction in the number of T1 enhancing lesions on brain magnetic resonance imaging. Three studies commented on adverse effects of vitamin D, with gastrointestinal adverse effects being the most frequently reported. The literature is limited by small study sizes (studies size ranged from 23 to 68 patients) and heterogeneity of dosing, form of vitamin D tested (vitamin D3 in four trials, and vitamin D2 in one), and outcome clinical measures. Therefore, a meta-analysis was not performed.
Conclusions
The evidence for vitamin D as a treatment for MS is inconclusive. Larger studies are warranted to assess the effect of vitamin D on clinical outcomes in patients with MS. We further encourage researchers to also test the effect of vitamin D on the health-related quality of life experienced by patients and their families.
doi:10.1159/000345122
PMCID: PMC3649517  PMID: 23257784
Multiple sclerosis; treatment; systematic review; vitamin D
5.  EBI metagenomics—a new resource for the analysis and archiving of metagenomic data 
Nucleic Acids Research  2013;42(D1):D600-D606.
Metagenomics is a relatively recently established but rapidly expanding field that uses high-throughput next-generation sequencing technologies to characterize the microbial communities inhabiting different ecosystems (including oceans, lakes, soil, tundra, plants and body sites). Metagenomics brings with it a number of challenges, including the management, analysis, storage and sharing of data. In response to these challenges, we have developed a new metagenomics resource (http://www.ebi.ac.uk/metagenomics/) that allows users to easily submit raw nucleotide reads for functional and taxonomic analysis by a state-of-the-art pipeline, and have them automatically stored (together with descriptive, standards-compliant metadata) in the European Nucleotide Archive.
doi:10.1093/nar/gkt961
PMCID: PMC3965009  PMID: 24165880
6.  Are depressive symptoms more common among British South Asian patients compared with British White patients with cancer? A cross-sectional survey 
BMJ Open  2013;3(6):e002650.
Objectives
This cross-sectional survey investigated whether there were ethnic differences in depressive symptoms among British South Asian (BSA) patients with cancer compared with British White (BW) patients during 9 months following presentation at a UK Cancer Centre. We examined associations between depressed mood, coping strategies and the burden of symptoms.
Design
Questionnaires were administered to 94 BSA and 185 BW recently diagnosed patients with cancer at baseline and at 3 and 9 months. In total, 53.8% of the BSA samples were born in the Indian subcontinent, 33% in Africa and 12.9% in the UK. Three screening tools for depression were used to counter concerns about ethnic bias and validity in linguistic translation. The Hospital Anxiety and Depression Scale (HADS-D), Patient Health Questionnaire-9 (both validated in Gujarati), Emotion Thermometers (including the Distress Thermometer (DT), Mini-MAC and the newly developed Cancer Insight and Denial questionnaire (CIDQ) were completed.
Setting
Leicestershire Cancer Centre, UK.
Participants
94 BSA and 185 BW recently diagnosed patients with cancer.
Results
BSA self-reported significantly higher rates of depressive symptoms compared with BW patients longitudinally (HADS-D ≥8: baseline: BSA 35.1% vs BW 16.8%, p=0.001; 3 months BSA 45.6% vs BW 20.8%, p=0.001; 9 months BSA 40.6% vs BW 15.3%, p=0.004). BSA patients used potentially maladaptive coping strategies more frequently than BW patients at baseline (hopelessness/helplessness p=0.005, fatalism p=0.0005, avoidance p=0.005; the CIDQ denial statement ‘I do not really believe I have cancer’ p=0.0005). BSA patients experienced more physical symptoms (DT checklist), which correlated with ethnic differences in depressive symptoms especially at 3 months.
Conclusions
Health professionals need to be aware of a greater probability of depressive symptomatology (including somatic symptoms) and how this may present clinically in the first 9 months after diagnosis if this ethnic disparity in mental well-being is to be addressed.
doi:10.1136/bmjopen-2013-002650
PMCID: PMC3686160  PMID: 23794580
Mental Health; Ethnicity; Depression
7.  Discounting of delayed rewards and executive dysfunction in individuals infected with hepatitis C 
Objective
Determine whether adults with hepatitis C, regardless of substance use disorder, are more likely to discount delayed rewards than adults without hepatitis C, and explore the relationship between delay discounting and neuropsychological functioning.
Methods
Procedures included clinical interviews, neuropsychological testing, and a delay discounting task.
Results
Regardless of substance abuse history, adults with hepatitis C were significantly more likely to choose smaller immediate rewards over larger delayed rewards. Delay discounting correlated with performance on executive functioning tasks.
Conclusions
Increased discounting is associated with broad executive dysfunction, suggesting that HCV associated executive dysfunction may lead to altered decision making style.
doi:10.1080/13803395.2010.499355
PMCID: PMC3615977  PMID: 20694872
hepatitis C; neuropsychology; impulsive behavior; substance-related disorders; delay discounting
8.  Efficiency of a Two-Item Pre-Screen to Reduce the Burden of Depression Screening in Pregnancy and Postpartum: An IMPLICIT Network Study 
Objective
Systems for efficient case finding of women with major depression during pregnancy and postpartum are needed. Here we assess the diagnostic accuracy of a modified 2-item patient health questionnaire (PHQ-2) as a pre-screen in assessing depression.
Methods
Cross-sectional assessments at 15 weeks’ gestation (n = 414), 30 weeks’ gestation (n = 334), and 6 to 16 weeks postpartum (n = 193) among women from a diverse set of races/ethnicities, participating in the IMPLICIT maternal care quality improvement network. The Edinburgh Postnatal Depression Scale score (≥13) was used as the criterion measure for the PHQ-2.
Results
A positive 2-item screen had sensitivity of 93%, 82%, and 80% and specificity of 75%, 80%, and 86% for Edinburgh Postnatal Depression Scale score of ≥13 for assessment at 15 and 30 weeks gestational age and postpartum, respectively. The positive/negative predictive values for the PHQ-2 were 44/98, 24/91, and 30/98 for each time point, respectively. Areas under the receiver operating characteristic curve analysis suggested that 2-item assessments at each time point had approximately equal diagnostic validity.
Conclusions
Two questions were efficient to rule out depression and reduced the need for further screening of approximately 60% to 80% of women, depending on the point in pregnancy or postpartum. A diagnostic interview follow-up of women screening positive is still required.
doi:10.3122/jabfm.2008.04.080048
PMCID: PMC3606919  PMID: 18612058
9.  A review of the potential therapeutic role of statins in the treatment of Alzheimer’s disease: current research and opinion 
Alzheimer’s disease is one of the most prevalent neurodegenerative disorders. However, there is no current treatment, which definitively influences disease progression over a sustained period. Numerous studies linking an increase in serum cholesterol, mainly during midlife, with the pathogenic process of Alzheimer’s disease have been published. Therefore, the role of statins as a therapy in this disorder may be of great interest. The aim of the present review is to summarize of the role of statins in the treatment of Alzheimer’s disease.
doi:10.2147/NDT.S29105
PMCID: PMC3540910  PMID: 23319866
animal models; epidemiology; HMGCoA-inhibitors; clinical trials; prevention; cognitive function
10.  Case identification of depression in patients with chronic physical health problems: a diagnostic accuracy meta-analysis of 113 studies 
The British Journal of General Practice  2011;61(593):e808-e820.
Background
Depression is more likely in patients with chronic physical illness, and is associated with increased rates of disability and mortality. Effective treatment of depression may reduce morbidity and mortality. The use of two stem questions for case finding in diabetes and coronary heart disease is advocated in the Quality and Outcomes Framework, and has become normalised into primary care.
Aim
To define the most effective tool for use in consultations to detect depression in people with chronic physical illness.
Design
Meta-analysis.
Method
The following data sources were searched: CENTRAL, CINAHL, Embase, HMIC, MEDLINE, PsycINFO, Web of Knowledge, from inception to July 2009. Three authors selected studies that examined identification tools and used an interview-based ICD (International Classification of Diseases) or DSM (Diagnostic and statistical Manual of Mental Disorders) diagnosis of depression as reference standard. At least two authors independently extracted study characteristics and outcome data and assessed methodological quality.
Results
A total of 113 studies met the eligibility criteria, providing data on 20 826 participants. It was found that two stem questions, PHQ-9 (Patient Health Questionnaire), the Zung, and GHQ-28 (General Health Questionnaire) were the optimal measures for case identification, but no method was sufficiently accurate to recommend as a definitive case-finding tool. Limitations were the moderate-to-high heterogeneity for most scales and the facts that few studies used ICD diagnoses as the reference standard, and that a variety of methods were used to determine DSM diagnoses.
Conclusion
Assessing both validity and ease of use, the two stem questions are the preferred method. However, clinicians should not rely on the two-questions approach alone, but should be confident to engage in a more detailed clinical assessment of patients who score positively.
doi:10.3399/bjgp11X613151
PMCID: PMC3223779  PMID: 22137418
depression; diagnosis; meta-analysis; primary care
11.  Genome3D: a UK collaborative project to annotate genomic sequences with predicted 3D structures based on SCOP and CATH domains 
Nucleic Acids Research  2012;41(D1):D499-D507.
Genome3D, available at http://www.genome3d.eu, is a new collaborative project that integrates UK-based structural resources to provide a unique perspective on sequence–structure–function relationships. Leading structure prediction resources (DomSerf, FUGUE, Gene3D, pDomTHREADER, Phyre and SUPERFAMILY) provide annotations for UniProt sequences to indicate the locations of structural domains (structural annotations) and their 3D structures (structural models). Structural annotations and 3D model predictions are currently available for three model genomes (Homo sapiens, E. coli and baker’s yeast), and the project will extend to other genomes in the near future. As these resources exploit different strategies for predicting structures, the main aim of Genome3D is to enable comparisons between all the resources so that biologists can see where predictions agree and are therefore more trusted. Furthermore, as these methods differ in whether they build their predictions using CATH or SCOP, Genome3D also contains the first official mapping between these two databases. This has identified pairs of similar superfamilies from the two resources at various degrees of consensus (532 bronze pairs, 527 silver pairs and 370 gold pairs).
doi:10.1093/nar/gks1266
PMCID: PMC3531217  PMID: 23203986
12.  GLOBAL AND LOCAL MORPHOMETRIC DIFFERENCES IN RECENTLY ABSTINENT METHAMPHETAMINE-DEPENDENT INDIVIDUALS 
NeuroImage  2010;50(4):1392-1401.
Methamphetamine (MA) is associated with behavioral and cognitive deficits that may be related to macrostructural abnormalities. Quantitative anatomical comparisons between controls and methamphetamine-dependent individuals have produced conflicting results. We examined local and global differences in brain structure in 61 abstinent methamphetamine-dependent individuals and 44 controls with voxel-based morphometry and tissue segmentation. We related regional differences in gray matter density and whole brain segmentation volumes to performance on a behavioral measure of impulsivity and group membership using multiple linear regression. Within the MA group, we related cortical and subcortical gray matter density to MA use history, length of abstinence and age of first use. Controls had greater density relative to MA in bilateral insula and left middle frontal gyrus. Impulsivity was higher in the MA group and, within all subjects, impulsivity was positively correlated with gray matter density in posterior cingulate cortex and ventral striatum and negatively correlated in left superior frontal gyrus. Length of abstinence from MA was associated with greater amygdalar density. Earlier age of first use of MA (in subjects who initiated use before age 21) was associated with smaller intracranial volume. The findings are consistent with multiple possible mechanisms including neuroadaptations due to addictive behavior, neuroinflammation as well as dopaminergic and serotonergic neurotoxicity.
doi:10.1016/j.neuroimage.2010.01.056
PMCID: PMC3478236  PMID: 20096794
13.  Metagenomic analysis: the challenge of the data bonanza 
Briefings in Bioinformatics  2012;13(6):743-746.
Several thousand metagenomes have already been sequenced, and this number is set to grow rapidly in the forthcoming years as the uptake of high-throughput sequencing technologies continues. Hand-in-hand with this data bonanza comes the computationally overwhelming task of analysis. Herein, we describe some of the bioinformatic approaches currently used by metagenomics researchers to analyze their data, the issues they face and the steps that could be taken to help overcome these challenges.
doi:10.1093/bib/bbs020
PMCID: PMC3504930  PMID: 22962339
metagenomics; next-generation sequencing (NGS); high-throughput sequencing (HTS); functional analysis; environmental bioinformatics
15.  The PRINTS database: a fine-grained protein sequence annotation and analysis resource—its status in 2012 
The PRINTS database, now in its 21st year, houses a collection of diagnostic protein family ‘fingerprints’. Fingerprints are groups of conserved motifs, evident in multiple sequence alignments, whose unique inter-relationships provide distinctive signatures for particular protein families and structural/functional domains. As such, they may be used to assign uncharacterized sequences to known families, and hence to infer tentative functional, structural and/or evolutionary relationships. The February 2012 release (version 42.0) includes 2156 fingerprints, encoding 12 444 individual motifs, covering a range of globular and membrane proteins, modular polypeptides and so on. Here, we report the current status of the database, and introduce a number of recent developments that help both to render a variety of our annotation and analysis tools easier to use and to make them more widely available.
Database URL: www.bioinf.manchester.ac.uk/dbbrowser/PRINTS/
doi:10.1093/database/bas019
PMCID: PMC3326521  PMID: 22508994
16.  International comparison of clinicians' ability to identify depression in primary care: meta-analysis and meta-regression of predictors 
Background
There are international differences in the epidemiology of depression and the performance of primary care physicians but the factors underlying these national differences are uncertain.
Aim
To examine the international variability in diagnostic performance of primary care physicians when diagnosing depression in primary care.
Design of study
A meta-analysis of unassisted clinical diagnoses against semi-structured interviews.
Method
A systematic literature search, critical appraisal, and pooled analysis were conducted and 25 international studies were identified involving 8917 individuals. A minimum of three independent studies per country were required to aid extrapolation.
Results
Clinicians in the Netherlands performed best at case finding (the ability to rule in cases of depression with minimal false positives) (AUC+ 0.735) and this was statistically significantly better than the ability of clinicians in Australia (AUC+ 0.622) and the US (AUC+ 0.653), who were the worst performers. Clinicians from Italy had intermediate case-finding abilities. Regarding screening (the ability to rule out cases of no depression with minimal false negatives) there were no strong differences. Looking at overall accuracy, primary care physicians in Italy and the Netherlands were most successful in their diagnoses and physicians from the US and Australia least successful (83.5%, 81.9%, 74.3%, and 67.0%, respectively). GPs in the UK appeared to have the lowest ability to detect depression, as a proportion of all cases of depression (45.6%; 95% CI = 27.7% to 64.2%). Several factors influenced detection accuracy including: collecting data on clinical outcomes; routinely comparing the clinical performance of staff; working in small practices; and having long waits to see a specialist.
Conclusion
Assuming these differences are representative, there appear to be international variations in the ability of primary care physicians to diagnose depression, but little differences in screening success. These might be explained by organisational factors.
doi:10.3399/bjgp11X556227
PMCID: PMC3026173  PMID: 21276327
depression; diagnostic accuracy; international; screening; sensitivity
17.  Manual GO annotation of predictive protein signatures: the InterPro approach to GO curation 
InterPro amalgamates predictive protein signatures from a number of well-known partner databases into a single resource. To aid with interpretation of results, InterPro entries are manually annotated with terms from the Gene Ontology (GO). The InterPro2GO mappings are comprised of the cross-references between these two resources and are the largest source of GO annotation predictions for proteins. Here, we describe the protocol by which InterPro curators integrate GO terms into the InterPro database. We discuss the unique challenges involved in integrating specific GO terms with entries that may describe a diverse set of proteins, and we illustrate, with examples, how InterPro hierarchies reflect GO terms of increasing specificity. We describe a revised protocol for GO mapping that enables us to assign GO terms to domains based on the function of the individual domain, rather than the function of the families in which the domain is found. We also discuss how taxonomic constraints are dealt with and those cases where we are unable to add any appropriate GO terms. Expert manual annotation of InterPro entries with GO terms enables users to infer function, process or subcellular information for uncharacterized sequences based on sequence matches to predictive models.
Database URL: http://www.ebi.ac.uk/interpro. The complete InterPro2GO mappings are available at: ftp://ftp.ebi.ac.uk/pub/databases/GO/goa/external2go/interpro2go
doi:10.1093/database/bar068
PMCID: PMC3270475  PMID: 22301074
18.  Schizophrenia: a multisystem disease? 
doi:10.1177/1359786810382059
PMCID: PMC2951587  PMID: 20923915
19.  Do deficits in cardiac care influence high mortality rates in schizophrenia? A systematic review and pooled analysis 
Journal of Psychopharmacology (Oxford, England)  2010;24(4_supplement):69-80.
We have previously documented inequalities in the quality of medical care provided to those with mental ill health but the implications for mortality are unclear. We aimed to test whether disparities in medical treatment of cardiovascular conditions, specifically receipt of medical procedures and receipt of prescribed medication, are linked with elevated rates of mortality in people with schizophrenia and severe mental illness. We undertook a systematic review of studies that examined medical procedures and a pooled analysis of prescribed medication in those with and without comorbid mental illness, focusing on those which recruited individuals with schizophrenia and measured mortality as an outcome. From 17 studies of treatment adequacy in cardiovascular conditions, eight examined cardiac procedures and nine examined adequacy of prescribed cardiac medication. Six of eight studies examining the adequacy of cardiac procedures found lower than average provision of medical care and two studies found no difference. Meta-analytic pooling of nine medication studies showed lower than average rates of prescribing evident for the following individual classes of medication; angiotensin converting enzyme inhibitors (n = 6, aOR = 0.779, 95% CI = 0.638–0.950, p = 0.0137), beta-blockers (n = 9, aOR = 0.844, 95% CI = 0.690–1.03, p = 0.1036) and statins (n = 5, aOR = 0.604, 95% CI = 0.408–0.89, p = 0.0117). No inequality was evident for aspirin (n = 7, aOR = 0.986, 95% CI = 0.7955–1.02, p = 0.382). Interestingly higher than expected prescribing was found for older non-statin cholesterol-lowering agents (n = 4, aOR = 1.55, 95% CI = 1.04–2.32, p = 0.0312). A search for outcomes in this sample revealed ten studies linking poor quality of care and possible effects on mortality in specialist settings. In half of the studies there was significantly higher mortality in those with mental ill health compared with controls but there was inadequate data to confirm a causative link. Nevertheless, indirect evidence supports the observation that deficits in quality of care are contributing to higher than expected mortality in those with severe mental illness (SMI) and schizophrenia. The quality of medical treatment provided to those with cardiac conditions and comorbid schizophrenia is often suboptimal and may be linked with avoidable excess mortality. Every effort should be made to deliver high-quality medical care to people with severe mental illness.
doi:10.1177/1359786810382056
PMCID: PMC2951596  PMID: 20923922
Mortality; quality of care; schizophrenia; severe mental illness; substance abuse
20.  PHQ-9 and PHQ-2 in Western Kenya 
doi:10.1007/s11606-009-0985-x
PMCID: PMC2695528  PMID: 19396499
21.  NICE may be discouraging detection of postpartum depression 
BMJ : British Medical Journal  2007;334(7593):550.
doi:10.1136/bmj.39150.424896.BE
PMCID: PMC1828305  PMID: 17363791
22.  InterPro: the integrative protein signature database 
Nucleic Acids Research  2008;37(Database issue):D211-D215.
The InterPro database (http://www.ebi.ac.uk/interpro/) integrates together predictive models or ‘signatures’ representing protein domains, families and functional sites from multiple, diverse source databases: Gene3D, PANTHER, Pfam, PIRSF, PRINTS, ProDom, PROSITE, SMART, SUPERFAMILY and TIGRFAMs. Integration is performed manually and approximately half of the total ∼58 000 signatures available in the source databases belong to an InterPro entry. Recently, we have started to also display the remaining un-integrated signatures via our web interface. Other developments include the provision of non-signature data, such as structural data, in new XML files on our FTP site, as well as the inclusion of matchless UniProtKB proteins in the existing match XML files. The web interface has been extended and now links out to the ADAN predicted protein–protein interaction database and the SPICE and Dasty viewers. The latest public release (v18.0) covers 79.8% of UniProtKB (v14.1) and consists of 16 549 entries. InterPro data may be accessed either via the web address above, via web services, by downloading files by anonymous FTP or by using the InterProScan search software (http://www.ebi.ac.uk/Tools/InterProScan/).
doi:10.1093/nar/gkn785
PMCID: PMC2686546  PMID: 18940856
23.  Do ultra-short screening instruments accurately detect depression in primary care? 
Background
Guidance from the National Institute for Health and Clinical Excellence recommends one or two questions as a possible screening method for depression. Ultra-short (one-, two-, three- or four-item) tests have appeal due to their simple administration but their accuracy has not been established.
Aim
To determine whether ultra-short screening instruments accurately detect depression in primary care.
Design of study
Pooled analysis and meta analysis.
Method
A literature search revealed 75 possible studies and from these, 22 STARD-compliant studies (Standards for Reporting of Diagnostic Accuracy) involving ultra-short tests were entered in the analysis.
Results
Meta-analysis revealed a performance accuracy better than chance (P<0.001). More usefully for clinicians, pooled analysis of single-question tests revealed an overall sensitivity of 32.0% and specificity of 97.0% (positive predictive value [PPV] was 55.6% and negative predictive value [NPV] was 92.3%). For two- and three- item tests, overall sensitivity on pooled analysis was 73.7% and specificity was 74.7% with a PPV of only 38.3% but a pooled NPV of 93.0%. The Youden index for single-item and multiple item tests was 0.289 and 0.47 respectively, suggesting superiority of multiple item tests. Re-analysis examining only ‘either or’ strategies improved the ‘rule in’ ability of two- and three-question tests (sensitivity 79.4% and NPV 94.7%) but at the expense of being able to rule out a possible diagnosis if the result was negative.
Conclusion
A one-question test identifies only three out of every 10 patients with depression in primary care, thus unacceptable if relied on alone. Ultra-short two- or three-question tests perform better, identifying eight out of 10 cases. This is at the expense of a high false-positive rate (only four out of 10 cases with a positive score are actually depressed). Ultra-short tests appear to be, at best, a method for ruling out a diagnosis and should only be used when there are sufficient resources for second-stage assessment of those who screen positive.
PMCID: PMC2034175  PMID: 17263931
depression; diagnostic techniques and procedures; meta-analysis; screening; sensitivity and specificity
24.  Comparison of protein coding gene contents of the fungal phyla Pezizomycotina and Saccharomycotina 
BMC Genomics  2007;8:325.
Background
Several dozen fungi encompassing traditional model organisms, industrial production organisms and human and plant pathogens have been sequenced recently and their particular genomic features analysed in detail. In addition comparative genomics has been used to analyse specific sub groups of fungi. Notably, analysis of the phylum Saccharomycotina has revealed major events of evolution such as the recent genome duplication and subsequent gene loss. However, little has been done to gain a comprehensive comparative view to the fungal kingdom. We have carried out a computational genome wide comparison of protein coding gene content of Saccharomycotina and Pezizomycotina, which include industrially important yeasts and filamentous fungi, respectively.
Results
Our analysis shows that based on genome redundancy, the traditional model organisms Saccharomyces cerevisiae and Neurospora crassa are exceptional among fungi. This can be explained by the recent genome duplication in S. cerevisiae and the repeat induced point mutation mechanism in N. crassa.
Interestingly in Pezizomycotina a subset of protein families related to plant biomass degradation and secondary metabolism are the only ones showing signs of recent expansion. In addition, Pezizomycotina have a wealth of phylum specific poorly characterised genes with a wide variety of predicted functions. These genes are well conserved in Pezizomycotina, but show no signs of recent expansion. The genes found in all fungi except Saccharomycotina are slightly better characterised and predicted to encode mainly enzymes. The genes specific to Saccharomycotina are enriched in transcription and mitochondrion related functions. Especially mitochondrial ribosomal proteins seem to have diverged from those of Pezizomycotina. In addition, we highlight several individual gene families with interesting phylogenetic distributions.
Conclusion
Our analysis predicts that all Pezizomycotina unlike Saccharomycotina can potentially produce a wide variety of secondary metabolites and secreted enzymes and that the responsible gene families are likely to evolve fast. Both types of fungal products can be of commercial value, or on the other hand cause harm to humans. In addition, a great number of novel predicted and known enzymes are found from all fungi except Saccharomycotina. Therefore further studies and exploitation of fungal metabolism appears very promising.
doi:10.1186/1471-2164-8-325
PMCID: PMC2045113  PMID: 17868481
25.  New developments in the InterPro database 
Nucleic Acids Research  2007;35(Database issue):D224-D228.
InterPro is an integrated resource for protein families, domains and functional sites, which integrates the following protein signature databases: PROSITE, PRINTS, ProDom, Pfam, SMART, TIGRFAMs, PIRSF, SUPERFAMILY, Gene3D and PANTHER. The latter two new member databases have been integrated since the last publication in this journal. There have been several new developments in InterPro, including an additional reading field, new database links, extensions to the web interface and additional match XML files. InterPro has always provided matches to UniProtKB proteins on the website and in the match XML file on the FTP site. Additional matches to proteins in UniParc (UniProt archive) are now available for download in the new match XML files only. The latest InterPro release (13.0) contains more than 13 000 entries, covering over 78% of all proteins in UniProtKB. The database is available for text- and sequence-based searches via a webserver (), and for download by anonymous FTP (). The InterProScan search tool is now also available via a web service at .
doi:10.1093/nar/gkl841
PMCID: PMC1899100  PMID: 17202162

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