Pathway-GPS and SIGORA: identifying relevant pathways based on the over-representation of their gene-pair signatures

peer-reviewedMotivation. Predominant pathway analysis approaches treat pathways as collections of individual genes and consider all pathway members as equally informative. As a result, at times spurious and misleading pathways are inappropriately identified as statistically significant, solely due to components that they share with the more relevant pathways. Results. We introduce the concept of Pathway Gene-Pair Signatures (Pathway-GPS) as pairs of genes that, as a combination, are specific to a single pathway. We devised and implemented a novel approach to pathway analysis, Signature Over-representation Analysis (SIGORA), which focuses on the statistically significant enrichment of Pathway-GPS in a user-specified gene list of interest. In a comparative evaluation of several published datasets, SIGORA outperformed traditional methods by delivering biologically more plausible and relevant results. Availability. An efficient implementation of SIGORA, as an R package with precompiled GPS data for several human and mouse pathway repositories is available for download from http://sigora.googlecode.com/svn/

InnateDB: systems biology of innate immunity and beyond—recent updates and continuing curation

peer-reviewedInnateDB (http://www.innatedb.com) is an integrated analysis platform that has been specifically designed to facilitate systems-level analyses of mammalian innate immunity networks, pathways and genes. In this article, we provide details of recent updates and improvements to the database. InnateDB now contains >196 000 human, mouse and bovine experimentally validated molecular interactions and 3000 pathway annotations of relevance to all mammalian cellular systems (i.e. not just immune relevant pathways and interactions). In addition, the InnateDB team has, to date, manually curated in excess of 18 000 molecular interactions of relevance to innate immunity, providing unprecedented insight into innate immunity networks, pathways and their component molecules. More recently, InnateDB has also initiated the curation of allergy- and asthma-related interactions. Furthermore, we report a range of improvements to our integrated bioinformatics solutions including web service access to InnateDB interaction data using Proteomics Standards Initiative Common Query Interface, enhanced Gene Ontology analysis for innate immunity, and the availability of new network visualizations tools. Finally, the recent integration of bovine data makes InnateDB the first integrated network analysis platform for this agriculturally important model organism.This work was supported by Genome BC through the Pathogenomics of Innate Immunity (PI2) project and by the Foundation for the National Institutes of Health and the Canadian Institutes of Health Research under the Grand Challenges in Global Health Research Initiative [Grand Challenges ID: 419]. Further funding was also provided by AllerGen grants 12ASI1 and 12B&B2. D.J.L. was funded in part during this project by a postdoctoral trainee award from the Michael Smith Foundation for Health Research (MSFHR). F.S.L.B. is a MSFHR Senior Scholar and R.E.W.H. holds a Canada Research Chair (CRC). Funding to enable bovine systems biology in InnateDB is provided by Teagasc [RMIS6018] and the Teagasc Walsh Fellowship scheme. IMEx is funded by the European Commission under the PSIMEx project [contract number FP7-HEALTH-2007-223411]. Funding for open access charge: Teagasc [RMIS6018]

Switching from a traditional undergraduate programme in (clinical) pharmacology and therapeutics to a problem-based learning programme

Purpose: The pharmacology and clinical pharmacology and therapeutics (CPT) education during the undergraduate medical curriculum of NOVA Medical School, Lisbon, Portugal, was changed from a traditional programme (i.e. discipline-based, lectures) to a problem-based learning (PBL) programme (i.e. integrated, case-based discussions) without an increase in teaching hours. The aim of this study was to investigate whether this change improved the prescribing competencies of final-year medical students. Methods: Final-year students from both programmes (2015 and 2019) were invited to complete a validated prescribing assessment and questionnaire. The assessment comprised 24 multiple-choice questions in three subdomains (working mechanism, side-effects and interactions/contraindications), and five clinical case scenarios of common diseases. The questionnaire focused on self-reported prescribing confidence, preparedness for future prescribing task and education received. Results: In total, 36 (22%) final-year medical students from the traditional programme and 54 (23%) from the PBL programme participated. Overall, students in the PBL programme had significantly higher knowledge scores than students in the traditional programme (76% (SD 9) vs 67% (SD 15); p = 0.002). Additionally, students in the PBL programme made significantly fewer inappropriate therapy choices (p = 0.023) and fewer erroneous prescriptions than did students in the traditional programme (p = 0.27). Students in the PBL programme felt more confident in prescribing, felt better prepared for prescribing as junior doctor and completed more drug prescriptions during their medical training. Conclusion: Changing from a traditional programme to an integrated PBL programme in pharmacology and CPT during the undergraduate medical curriculum may improve the prescribing competencies of final-year students.publishersversionpublishe

Bioinformatics advances in saliva diagnostics

There is a need recognized by the National Institute of Dental & Craniofacial Research and the National Cancer Institute to advance basic, translational and clinical saliva research. The goal of the Salivaomics Knowledge Base (SKB) is to create a data management system and web resource constructed to support human salivaomics research. To maximize the utility of the SKB for retrieval, integration and analysis of data, we have developed the Saliva Ontology and SDxMart. This article reviews the informatics advances in saliva diagnostics made possible by the Saliva Ontology and SDxMart

The clustering of intermediate redshift quasars as measured by the Baryon Oscillation Spectroscopic Survey

We measure the quasar two-point correlation function over the redshift range 2.2<z<2.8 using data from the Baryon Oscillation Spectroscopic Survey. We use a homogeneous subset of the data consisting of 27,129 quasars with spectroscopic redshifts---by far the largest such sample used for clustering measurements at these redshifts to date. The sample covers 3,600 square degrees, corresponding to a comoving volume of 9.7(Gpc/h)^3 assuming a fiducial LambdaCDM cosmology, and it has a median absolute i-band magnitude of -26, k-corrected to z=2. After accounting for redshift errors we find that the redshift space correlation function is fit well by a power-law of slope -2 and amplitude s_0=(9.7\pm 0.5)Mpc/h over the range 3<s<25Mpc/h. The projected correlation function, which integrates out the effects of peculiar velocities and redshift errors, is fit well by a power-law of slope -1 and r_0=(8.4\pm 0.6)Mpc/h over the range 4<R<16Mpc/h. There is no evidence for strong luminosity or redshift dependence to the clustering amplitude, in part because of the limited dynamic range in our sample. Our results are consistent with, but more precise than, previous measurements at similar redshifts. Our measurement of the quasar clustering amplitude implies a bias factor of b~3.5 for our quasar sample. We compare the data to models to constrain the manner in which quasars occupy dark matter halos at z~2.4 and infer that such quasars inhabit halos with a characteristic mass of ~10^{12}Msun/h with a duty cycle for the quasar activity of 1 per cent.Comment: 20 pages, 18 figures. Minor modifications to match version accepted by journa

An emerging field of research: challenges in pediatric decision making

There is growing interest in pediatric decision science, spurred by policies advocating for children's involvement in medical decision making. Challenges specific to pediatric decision research include the dynamic nature of child participation in decisions due to the growth and development of children, the family context of all pediatric decisions, and the measurement of preferences and outcomes that may inform decision making in the pediatric setting. The objectives of this article are to describe each of these challenges, to provide decision researchers with insight into pediatric decision making, and to establish a blueprint for future research that will contribute to high-quality pediatric medical decision making. Much work has been done to address gaps in pediatric decision science, but substantial work remains. Understanding and addressing the challenges that exist in pediatric decision making may foster medical decision-making science across the age spectrum

Key Learning Outcomes for Clinical Pharmacology and Therapeutics Education in Europe:A Modified Delphi Study

Harmonizing clinical pharmacology and therapeutics (CPT) education in Europe is necessary to ensure that the prescribing competency of future doctors is of a uniform high standard. As there are currently no uniform requirements, our aim was to achieve consensus on key learning outcomes for undergraduate CPT education in Europe. We used a modified Delphi method consisting of three questionnaire rounds and a panel meeting. A total of 129 experts from 27 European countries were asked to rate 307 learning outcomes. In all, 92 experts (71%) completed all three questionnaire rounds, and 33 experts (26%) attended the meeting. 232 learning outcomes from the original list, 15 newly suggested and 5 rephrased outcomes were included. These 252 learning outcomes should be included in undergraduate CPT curricula to ensure that European graduates are able to prescribe safely and effectively. We provide a blueprint of a European core curriculum describing when and how the learning outcomes might be acquired.</p

The breakdown of the Nagaoka phase in the 2D t-J model

In the limit of weak exchange, J, at low hole concentration, the ground state of the 2D t-J model is believed to be ferromagnetic. We study the leading instability of this Nagaoka state, which emerges with increasing J. Both exact diagonalization of small clusters, and a semiclassical analytical calculation of larger systems show that above a certain critical value of the exchange, Nagaoka's state is unstable to phase separation. In a finite-size system a bubble of antiferromagnetic Mott insulator appears in the ground state above this threshold. The size of this bubble depends on the hole concentration and scales as a power of the system size, N