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

Evidence of Bordetella pertussis infection in vaccinated 1-year-old Danish children

We measured IgA and IgG antibodies to pertussis toxin (PT) and filamentous hemagglutinin (FHA) in sera from 203 1-year-old children who had received one to three doses of a monocomponent PT toxoid vaccine. Ten children (5%) had IgA antibody to PT indicating recent infection; seven of these children had received three doses of vaccine. PT IgA responders did not have significantly longer coughing episodes than PT IgA non-responders. Since an IgA antibody response occurs in only ∼50% of infected children, the actual infection rate in our cohort is estimated to ∼10%. The apparent high Bordetella pertussis infection rate in Danish infants suggests that the monocomponent PT toxoid vaccine used in Denmark has limited efficacy against B. pertussis infection. A prospective immunization study comparing a multi-component vaccine with the present monocomponent PT toxoid vaccine should be undertaken

Infectious Disease Ontology

Technological developments have resulted in tremendous increases in the volume and diversity of the data and information that must be processed in the course of biomedical and clinical research and practice. Researchers are at the same time under ever greater pressure to share data and to take steps to ensure that data resources are interoperable. The use of ontologies to annotate data has proven successful in supporting these goals and in providing new possibilities for the automated processing of data and information. In this chapter, we describe different types of vocabulary resources and emphasize those features of formal ontologies that make them most useful for computational applications. We describe current uses of ontologies and discuss future goals for ontology-based computing, focusing on its use in the field of infectious diseases. We review the largest and most widely used vocabulary resources relevant to the study of infectious diseases and conclude with a description of the Infectious Disease Ontology (IDO) suite of interoperable ontology modules that together cover the entire infectious disease domain

Herpesvirus-Associated Acute Urticaria: An Age Matched Case-Control Study

Background Acute and recurrent acute urticaria are often associated with multiple factors including infections and recent data suggest a role for herpesviruses. Objective To test the null hypothesis, that is, there is no association of herpesvirus infections with urticaria. Methods Thirty-seven patients between one month and 15 years of age were age matched to 37 controls who were healthy or had mild acute respiratory infections but without urticaria. Patients and controls were followed for 1 to 6 years. Diagnostic studies included DNA detection by real-time PCR for herpes simplex virus (HSV) types 1 and 2, Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human herpesvirus-6 (HHV-6). Tests for other infections included adenovirus, parvovirus B 19, respiratory syncytial virus, influenza A, Group A streptococci, rotavirus, and parasites. Results Specific infections were diagnosed in 26 of 37 cases and among 9 of 37 control children (P=0.0002). Single or concomitant herpesvirus infections occurred in 24 cases and in 4 controls (65% vs 11 %, p=0.0003). Cases had 10 HHV-6 infections, 8 CMV infections, 5 EBV infections, and 4 HSV-1 infections. Conclusion Herpesvirus infections are associated with acute or recurrent acute urticaria

STORIES Statement: publication standards for healthcare education evidence synthesis

Fully copy of the STORIES statement - a checklist of reporting guidance for health education evidence synthesis Structured approach for Reporting In health education of Evidence Synthesis Background Evidence synthesis techniques in healthcare education have been enhanced through the activities of experts in the field and the Best Evidence Medical Education (BEME) collaborative. Despite this, significant heterogeneity in techniques and reporting of healthcare education systematic review still exist and limit the usefulness of such reports. The aim of this project was to produce the STORIES (STructured apprOach to the Reporting In healthcare education of Evidence Synthesis) statement to offer a guide for reporting evidence synthesis in health education for use by authors and journal editors. Methods A review of existing published evidence synthesis consensus statements was undertaken. A modified Delphi process was used. In stage one, expert participants were asked to state whether common existing items identified were relevant, to suggest relevant texts and specify any items they feel should be included. The results were analysed and a second stage commenced where all synthesised items were presented and participants asked to state whether they should be included or amend as needed. After further analysis, the full statement was sent for final review and comment. Results Nineteen experts participated in the panel from 35 invitations. Thirteen text sources were proposed, six existing items amended and twelve new items synthesised. After stage two, 25 amended consensus items were proposed for inclusion. The final statement contains several items unique to this context, including description of relevant conceptual frameworks or theoretical constructs, description of qualitative methodologies with rationale for their choice and presenting the implications for educators in practice of the results obtained. Conclusions An international expert panel has agreed upon a consensus statement of 25 items for the reporting of evidence synthesis within healthcare education. This unique set of items is focused on context, rather than a specific methodology. This statement can be used for those writing for publication and reviewing such manuscripts to ensure reporting supports and best informs the wider healthcare education community

Signatures of large composite Dark Matter states

We investigate the interactions of large composite dark matter (DM) states with the Standard Model (SM) sector. Elastic scattering with SM nuclei can be coherently enhanced by factors as large as A^2, where A is the number of constituents in the composite state (there exist models in which DM states of very large A > 10^8 may be realised). This enhancement, for a given direct detection event rate, weakens the expected signals at colliders by up to 1/A. Moreover, the spatially extended nature of the DM states leads to an additional, characteristic, form factor modifying the momentum dependence of scattering processes, altering the recoil energy spectra in direct detection experiments. In particular, energy recoil spectra with peaks and troughs are possible, and such features could be confirmed with only O(50) events, independently of the assumed halo velocity distribution. Large composite states also generically give rise to low-energy collective excitations potentially relevant to direct detection and indirect detection phenomenology. We compute the form factor for a generic class of such excitations - quantised surface modes - finding that they can lead to coherently-enhanced, but generally sub-dominant, inelastic scattering in direct detection experiments. Finally, we study the modifications to capture rates in astrophysical objects that follow from the elastic form factor, as well as the effects of inelastic interactions between DM states once captured. We argue that inelastic interactions may lead to the DM collapsing to a dense configuration at the centre of the object.Comment: 30 pages, 5 figures, v2; references and minor additional comments adde

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Seroprevalence of Immunoglobulin G antibodies against pertussis toxin among asymptomatic medical students in the west of Iran: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>Pertussis is a highly communicable, vaccine-preventable respiratory infection. Immune response against this disease can be induced by infection or vaccination. Protection after childhood vaccination is minimal after ten years. Our aim was to assess pertussis immunity state in a population of healthy young medical students.</p> <p>Methods</p> <p>In this seroepidemiological survey, blood samples were obtained from 163 first-year medical students in Hamedan University, Iran. Serum level of IgG against pertussis toxin (IgG-PT) was measured by Enzyme-Linked Immunosorbent Assay (ELISA) method. For qualitative assessment, IgG-PT levels more than 24 unit (U)/ml were considered positive. Data was analysed qualitatively and quantitatively considering gender and age groups.</p> <p>Results</p> <p>There were 83 males and 80 females, with a mean age of 19.48 years, Prevalence of IgG-PT was 47.6% with mean level of 71.7 u/ml (95% confidence interval: 68.1–75.3). No statistically significant difference was observed with respect to sero-positivity of IgG-PT between males and females (45 cases (54%) vs. 34 cases (42%); P = 0.06). Mean IgG-PT levels in males and females were 84 U/ml and 58.8 U/ml, respectively (P = 0.91).</p> <p>Conclusion</p> <p>A considerable proportion of our study population with a positive history of childhood vaccination for pertussis was not serologically immune to pertussis. A booster dose of acellular pertussis vaccine may be indicated in Iranian, medical students regarding their serologic conditions and outstanding role in health care systems.</p

Comparative epidemiologic characteristics of pertussis in 10 Central and Eastern European countries, 2000-2013

Publisher Copyright: © 2016 Heininger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.We undertook an epidemiological survey of the annual incidence of pertussis reported from 2000 to 2013 in ten Central and Eastern European countries to ascertain whether increased pertussis reports in some countries share common underlying drivers or whether there are specific features in each country. The annual incidence of pertussis in the participating countries was obtained from relevant government institutions and/or national surveillance systems. We reviewed the changes in the pertussis incidence rates in each country to explore differences and/or similarities between countries in relation to pertussis surveillance; case definitions for detection and confirmation of pertussis; incidence and number of cases of pertussis by year, overall and by age group; population by year, overall and by age group; pertussis immunization schedule and coverage, and switch from whole-cell pertussis vaccines (wP) to acellular pertussis vaccines (aP). There was heterogeneity in the reported annual incidence rates and trends observed across countries. Reported pertussis incidence rates varied considerably, ranging from 0.01 to 96 per 100,000 population, with the highest rates generally reported in Estonia and the lowest in Hungary and Serbia. The greatest burden appears for the most part in infants (<1 year) in Bulgaria, Hungary, Latvia, Romania, and Serbia, but not in the other participating countries where the burden may have shifted to older children, though surveillance of adults may be inappropriate. There was no consistent pattern associated with the switch from wP to aP vaccines on reported pertussis incidence rates. The heterogeneity in reported data may be related to a number of factors including surveillance system characteristics or capabilities, different case definitions, type of pertussis confirmation tests used, public awareness of the disease, as well as real differences in the magnitude of the disease, or a combination of these factors. Our study highlights the need to standardize pertussis detection and confirmation in surveillance programs across Europe, complemented with carefully-designed seroprevalence studies using the same protocols and methodologies.publishersversionPeer reviewe

How Genomics Is Changing What We Know About the Evolution and Genome of Bordetella pertussis

The evolution of Bordetella pertussis from a common ancestor similar to Bordetella bronchiseptica has occurred through large-scale gene loss, inactivation and rearrangements, largely driven by the spread of insertion sequence element repeats throughout the genome. B. pertussis is widely considered to be monomorphic, and recent evolution of the B. pertussis genome appears to, at least in part, be driven by vaccine-based selection. Given the recent global resurgence of whooping cough despite the wide-spread use of vaccination, a more thorough understanding of B. pertussis genomics could be highly informative. In this chapter we discuss the evolution of B. pertussis, including how vaccination is changing the circulating B. pertussis population at the gene-level, and how new sequencing technologies are revealing previously unknown levels of inter- and intra-strain variation at the genome-level