BioPartsDB: a synthetic biology workflow web-application for education and research

Synthetic biology has become a widely used technology, and expanding applications in research, education and industry require progress tracking for team-based DNA synthesis projects. Although some vendors are beginning to supply multi-kilobase sequence-verified constructs, synthesis workflows starting with short oligos remain important for cost savings and pedagogical benefit. We developed BioPartsDB as an open source, extendable workflow management system for synthetic biology projects with entry points for oligos and larger DNA constructs and ending with sequence-verified clones

MCL-CAw: A refinement of MCL for detecting yeast complexes from weighted PPI networks by incorporating core-attachment structure

Abstract Background The reconstruction of protein complexes from the physical interactome of organisms serves as a building block towards understanding the higher level organization of the cell. Over the past few years, several independent high-throughput experiments have helped to catalogue enormous amount of physical protein interaction data from organisms such as yeast. However, these individual datasets show lack of correlation with each other and also contain substantial number of false positives (noise). Over these years, several affinity scoring schemes have also been devised to improve the qualities of these datasets. Therefore, the challenge now is to detect meaningful as well as novel complexes from protein interaction (PPI) networks derived by combining datasets from multiple sources and by making use of these affinity scoring schemes. In the attempt towards tackling this challenge, the Markov Clustering algorithm (MCL) has proved to be a popular and reasonably successful method, mainly due to its scalability, robustness, and ability to work on scored (weighted) networks. However, MCL produces many noisy clusters, which either do not match known complexes or have additional proteins that reduce the accuracies of correctly predicted complexes. Results Inspired by recent experimental observations by Gavin and colleagues on the modularity structure in yeast complexes and the distinctive properties of "core" and "attachment" proteins, we develop a core-attachment based refinement method coupled to MCL for reconstruction of yeast complexes from scored (weighted) PPI networks. We combine physical interactions from two recent "pull-down" experiments to generate an unscored PPI network. We then score this network using available affinity scoring schemes to generate multiple scored PPI networks. The evaluation of our method (called MCL-CAw) on these networks shows that: (i) MCL-CAw derives larger number of yeast complexes and with better accuracies than MCL, particularly in the presence of natural noise; (ii) Affinity scoring can effectively reduce the impact of noise on MCL-CAw and thereby improve the quality (precision and recall) of its predicted complexes; (iii) MCL-CAw responds well to most available scoring schemes. We discuss several instances where MCL-CAw was successful in deriving meaningful complexes, and where it missed a few proteins or whole complexes due to affinity scoring of the networks. We compare MCL-CAw with several recent complex detection algorithms on unscored and scored networks, and assess the relative performance of the algorithms on these networks. Further, we study the impact of augmenting physical datasets with computationally inferred interactions for complex detection. Finally, we analyse the essentiality of proteins within predicted complexes to understand a possible correlation between protein essentiality and their ability to form complexes. Conclusions We demonstrate that core-attachment based refinement in MCL-CAw improves the predictions of MCL on yeast PPI networks. We show that affinity scoring improves the performance of MCL-CAw.http://deepblue.lib.umich.edu/bitstream/2027.42/78256/1/1471-2105-11-504.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78256/2/1471-2105-11-504-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78256/3/1471-2105-11-504-S2.ZIPhttp://deepblue.lib.umich.edu/bitstream/2027.42/78256/4/1471-2105-11-504.pdfPeer Reviewe

Fluorescence-Based Methods for Detecting Caries Lesions: Systematic Review, Meta-Analysis and Sources of Heterogeneity

Background Fluorescence-based methods have been proposed to aid caries lesion detection. Summarizing and analysing findings of studies about fluorescence-based methods could clarify their real benefits. Objective We aimed to perform a comprehensive systematic review and meta-analysis to evaluate the accuracy of fluorescence-based methods in detecting caries lesions. Data Source Two independent reviewers searched PubMed, Embase and Scopus through June 2012 to identify papers/articles published. Other sources were checked to identify non-published literature. Study Eligibility Criteria, Participants and Diagnostic Methods The eligibility criteria were studies that: (1) have assessed the accuracy of fluorescence-based methods of detecting caries lesions on occlusal, approximal or smooth surfaces, in both primary or permanent human teeth, in the laboratory or clinical setting; (2) have used a reference standard; and (3) have reported sufficient data relating to the sample size and the accuracy of methods. Study Appraisal and Synthesis Methods A diagnostic 2×2 table was extracted from included studies to calculate the pooled sensitivity, specificity and overall accuracy parameters (Diagnostic Odds Ratio and Summary Receiver-Operating curve). The analyses were performed separately for each method and different characteristics of the studies. The quality of the studies and heterogeneity were also evaluated. Results Seventy five studies met the inclusion criteria from the 434 articles initially identified. The search of the grey or non-published literature did not identify any further studies. In general, the analysis demonstrated that the fluorescence-based method tend to have similar accuracy for all types of teeth, dental surfaces or settings. There was a trend of better performance of fluorescence methods in detecting more advanced caries lesions. We also observed moderate to high heterogeneity and evidenced publication bias. Conclusions Fluorescence-based devices have similar overall performance; however, better accuracy in detecting more advanced caries lesions has been observed

Diagnostic and preventive service trends in private general practice: 1983-1984 to 1998-1999

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: Aggregate trends have indicated increases in the provision of diagnostic and preventive services but there have been few reports based on their component sub-categories. The aims of this study were to investigate time trends in the provision of sub-categories of diagnostic and preventive services across a 15-year period. Methods: A random sample of Australian dentists was surveyed by mailed questionnaire in 1983-1984, 1988-1989, 1993-1994 and 1998-1999 (response rates 71-75 per cent). Data were weighted to provide representative estimates for the age by sex distribution of private general practitioners in 1983, 1988, 1993 and 1998. Results: Rates per visit were higher, Poisson regression, P<0.05, in 1998-1999 compared to baseline for examinations, radiographs, prophylaxis and topical fluoride. Diagnostic and preventive service rates varied by age of patient: compared to patients aged 65+ years, examinations were higher among children aged <5 years to adults aged 25-44 years, radiographs were lower among children <5 years and 5-11 years but higher among adults aged from 18-24 years to 45-64 years, prophylaxis services were lower among children <5 years but higher among adolescents 12-17 years to adults aged 45-64 years, while topical fluoride was higher among children 5-11 years and adolescents 12-17 years. Conclusions: Examination, radiograph, prophylaxis, and topical fluoride rates increased over the study period. While examination rates increased for both children and adults, and prophylaxis rates increased for adolescents and adults, rates for radiographs and topical fluoride only increased for adults. Agespecific changes in service rates over time indicate the effect of changing oral health status and population demographics on service provision.DS Brennan, AJ Spence

Longitudinal comparison of factors influencing choice of dental treatment by private general practitioners

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: Service rate variations and appropriateness of care issues have focused attention on factors that influence treatment decisions. The aims of this study were to examine what factors dentists consider in choosing alternative treatments, the stability of these factors over time and whether stability of treatment choice was related to age of dentist. Methods: Baseline data were collected by mailed self-complete questionnaires from a random sample of Australian dentists (response rate=60.3 per cent, n=345 private general practitioners provided service data from a typical day) in 1997–1998 and followup data were collected in 2004 (response rate=76.8 per cent, n=177 matched longitudinal cases). Results: The most frequent factors considered important across six alternative treatment pair choice scenarios were caries rate for ‘exam v. x-ray’, age of patient for ‘preventive v. restorative intervention’, cost of treatment for ‘crown v. buildup’, ‘root canal v. extraction’ and ‘bridge v. denture’, and calculus for ‘prophylaxis v. scaling’. The only differences over time were (t-test, P<0.05): higher proportions of responses in the mouth status group at follow-up for ‘exam v. x-ray’; higher proportions of responses in the visit history group at follow-up for ‘preventive v. restorative intervention’; a lower proportion of responses in the caries group at follow-up for ‘crown v. build-up’; and a higher proportion of responses in the treatment constraints group at follow-up for ‘prophylaxis v. scaling’. Conclusions: While a wide range of responses were offered as factors influencing the choice of alternative treatments, cost of treatment was a major consideration in situations where significantly cheaper alternatives existed, while patient preference was commonly included as a secondary consideration across a wide range of treatment choice scenarios. The treatment choice responses showed a high degree of stability over time across all age groups of dentists, suggesting that if routines are developed these are established before or soon after graduation as a dentist.DS Brennan, AJ Spence

Reducing Alaska Native paediatric oral health disparities: a systematic review of oral health interventions and a case study on multilevel strategies to reduce sugar-sweetened beverage intake

Background. Tooth decay is the most common paediatric disease and there is a serious paediatric tooth decay epidemic in Alaska Native communities. When untreated, tooth decay can lead to pain, infection, systemic health problems, hospitalisations and in rare cases death, as well as school absenteeism, poor grades and low quality-of-life. The extent to which population-based oral health interventions have been conducted in Alaska Native paediatric populations is unknown. Objective. To conduct a systematic review of oral health interventions aimed at Alaska Native children below age 18 and to present a case study and conceptual model on multilevel intervention strategies aimed at reducing sugar-sweetened beverage (SSB) intake among Alaska Native children. Design. Based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Statement, the terms &#x201C;Alaska Native&#x201D;, &#x201C;children&#x201D; and &#x201C;oral health&#x201D; were used to search Medline, Embase, Web of Science, GoogleScholar and health foundation websites (1970&#x2013;2012) for relevant clinical trials and evaluation studies. Results. Eighty-five studies were found in Medline, Embase and Web of Science databases and there were 663 hits in GoogleScholar. A total of 9 publications were included in the qualitative review. These publications describe 3 interventions that focused on: reducing paediatric tooth decay by educating families and communities; providing dental chemotherapeutics to pregnant women; and training mid-level dental care providers. While these approaches have the potential to improve the oral health of Alaska Native children, there are unique challenges regarding intervention acceptability, reach and sustainability. A case study and conceptual model are presented on multilevel strategies to reduce SSB intake among Alaska Native children. Conclusions. Few oral health interventions have been tested within Alaska Native communities. Community-centred multilevel interventions are promising approaches to improve the oral and systemic health of Alaska Native children. Future investigators should evaluate the feasibility of implementing multilevel interventions and policies within Alaska Native communities as a way to reduce children&#x0027;s health disparities

Dormancy within Staphylococcus epidermidis biofilms : a transcriptomic analysis by RNA-seq

The proportion of dormant bacteria within Staphylococcus epidermidis biofilms may determine its inflammatory profile. Previously, we have shown that S. epidermidis biofilms with higher proportions of dormant bacteria have reduced activation of murine macrophages. RNA-sequencing was used to identify the major transcriptomic differences between S. epidermidis biofilms with different proportions of dormant bacteria. To accomplish this goal, we used an in vitro model where magnesium allowed modulation of the proportion of dormant bacteria within S. epidermidis biofilms. Significant differences were found in the expression of 147 genes. A detailed analysis of the results was performed based on direct and functional gene interactions. Biological processes among the differentially expressed genes were mainly related to oxidation-reduction processes and acetyl-CoA metabolic processes. Gene set enrichment revealed that the translation process is related to the proportion of dormant bacteria. Transcription of mRNAs involved in oxidation-reduction processes was associated with higher proportions of dormant bacteria within S. epidermidis biofilm. Moreover, the pH of the culture medium did not change after the addition of magnesium, and genes related to magnesium transport did not seem to impact entrance of bacterial cells into dormancy.The authors thank Stephen Lorry at Harvard Medical School for providing CLC Genomics software. This work was funded by Fundacao para a Ciencia e a Tecnologia (FCT) and COMPETE grants PTDC/BIA-MIC/113450/2009, FCOMP-01-0124-FEDER-014309, FCOMP-01-0124-FEDER-022718 (FCT PEst-C/SAU/LA0002/2011), QOPNA research unit (project PEst-C/QUI/UI0062/2011), and CENTRO-07-ST24-FEDER-002034. The following authors had an individual FCT fellowship: VC (SFRH/BD/78235/2011) and AF (2SFRH/BD/62359/2009)

Managing caries:the need to close the gap between the evidence base and current practice

Underpinned by a changing knowledge of the aetiology of caries and its sequelae, and assisted by established and advancing dental materials, there is growing evidence supporting less invasive management of dental caries based on the principles of minimal intervention dentistry. This narrative review assesses both the evidence and the adoption of less invasive caries management strategies and describes ways in which the gap between evidence and practice might be overcome. While there is increasing data supporting less invasive management of carious lesions, these are not standard in most dental practices worldwide. Usually, clinical studies focused on efficacy as outcome, and did not take into consideration the views and priorities of other stakeholders, such as primary care dentists, educators, patients and those financing services. Involving these stakeholders into study design and demonstrating the broader advantages of new management strategies might improve translation of research into practice. In theory, clinical dentists can rely on a growing evidence in cariology regarding less invasive management options. In practice, further factors seem to impede adoption of these strategies. Future research should address these factors by involving major stakeholders and investigating their prioritised outcomes to narrow or close the evidence gap.</p

Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesOver the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) <1.15).We conducted a large-scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls).We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P = 9 × 10(-6)). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a 'neurodevelopmental hub' on chromosome 8p11.23.This study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental-related genes such as EXT1, ASTN2, MACROD2, and HDAC4.National Institutes of Mental Health (NIMH, USA) ACE Network Autism Genetic Resource Exchange (AGRE) is a program of Autism Speaks (USA) The Autism Genome Project (AGP) from Autism Speaks (USA) Canadian Institutes of Health Research (CIHR), Genome Canada Health Research Board (Ireland) Hilibrand Foundation (USA) Medical Research Council (UK) National Institutes of Health (USA) Ontario Genomics Institute University of Toronto McLaughlin Centre Simons Foundation Johns Hopkins Autism Consortium of Boston NLM Family foundation National Institute of Health grants National Health Medical Research Council Scottish Rite Spunk Fund, Inc. Rebecca and Solomon Baker Fund APEX Foundation National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD) endowment fund of the Nancy Pritzker Laboratory (Stanford) Autism Society of America Janet M. Grace Pervasive Developmental Disorders Fund The Lundbeck Foundation universities and university hospitals of Aarhus and Copenhagen Stanley Foundation Centers for Disease Control and Prevention (CDC) Netherlands Scientific Organization Dutch Brain Foundation VU University Amsterdam Trinity Centre for High Performance Computing through Science Foundation Ireland Autism Genome Project (AGP) from Autism Speak