Discovery and characterisation of dietary patterns in two Nordic countries. Using non-supervised and supervised multivariate statistical techniques to analyse dietary survey data

This Nordic study encompasses multivariate data analysis (MDA) of preschool Danish as well as pre- and elementary school Swedish consumers. Contrary to other counterparts the study incorporates two separate MDA varieties - Pattern discovery (PD) and predictive modelling (PM). PD, i.e. hierarchical cluster analysis (HCA) and factor analysis (using PCA), helped identifying distinct consumer aggregations and relationships across food groups, respectively, whereas PM enabled the disclosure of deeply entrenched associations. 17 clusters - here defined as dietary prototypes - were identified by means of HCA in the entire bi-national data set. These prototypes underwent further processing, which disclosed several intriguing consumption data relationships: Striking disparity between consumption patterns of Danish and Swedish preschool children was unveiled and further dissected by PM. Two prudent and mutually similar dietary prototypes appeared among each of two Swedish elementary school children data subsets. Dietary prototypes rich in sweetened soft beverages appeared among Danish and Swedish children alike. The results suggest prototype-specific risk assessment and study design

EVALLER: a web server for in silico assessment of potential protein allergenicity

Bioinformatics testing approaches for protein allergenicity, involving amino acid sequence comparisons, have evolved appreciably over the last several years to increased sophistication and performance. EVALLER, the web server presented in this article is based on our recently published ‘Detection based on Filtered Length-adjusted Allergen Peptides’ (DFLAP) algorithm, which affords in silico determination of potential protein allergenicity of high sensitivity and excellent specificity. To strengthen bioinformatics risk assessment in allergology EVALLER provides a comprehensive outline of its judgment on a query protein's potential allergenicity. Each such textual output incorporates a scoring figure, a confidence numeral of the assignment and information on high- or low-scoring matches to identified allergen-related motifs, including their respective location in accordingly derived allergens. The interface, built on a modified Perl Open Source package, enables dynamic and color-coded graphic representation of key parts of the output. Moreover, pertinent details can be examined in great detail through zoomed views. The server can be accessed at http://bioinformatics.bmc.uu.se/evaller.html

Novel Computational Analyses of Allergens for Improved Allergenicity Risk Assessment and Characterization of IgE Reactivity Relationships

Immunoglobulin E (IgE) mediated allergy is a major and seemingly increasing health problem in the Western countries. The combined usage of databases of molecular and clinical information on allergens (allergenic proteins) as well as new experimental platforms capable of generating huge amounts of allergy-related data from a single blood test holds great potential to enhance our knowledge of this complex disease. To maximally benefit from this development, however, both novel and improved methods for computational analysis are urgently required. This thesis concerns two types of important and practical computational analyses of allergens: allergenicity/IgE-cross-reactivity risk assessment and characterization of IgE-reactivity patterns. Both directions rely on development and implementation of bioinformatics and statistical learning algorithms, which are applied to either amino acid sequence information of allergenic proteins or on quantified human blood serum levels of specific IgE-antibodies to allergen preparations (purified extracts of allergenic sources, such as e.g. peanut or birch). The main application for computational risk assessment of allergenicity is to prevent unintentional introduction of allergen-encoding transgenes in genetically modified (GM) food crops. Two separate classification procedures for potential protein allergenicity are introduced. Both protocols rely on multivariate classification algorithms that are educated to discriminate allergens from presumable non-allergens based on their amino acid sequence. Both classification procedures are thoroughly evaluated and the second protocol shows state-of-the-art performance in comparison to current top-ranked methods. Moreover, several pitfalls in performance estimation of classifiers are demonstrated and procedures to circumvent these are suggested. Visualization and characterization of IgE-reactivity patterns among allergen preparations are enabled by application of bioinformatics and statistical learning methods to a multivariate dataset holding recorded blood serum IgE-levels of over 1000 sensitized individuals, each measured to 89 allergen preparations. Moreover, a novel framework for divisive hierarchical clustering including graphical representation of the resulting output is introduced, which greatly simplifies analysis of the abovementioned dataset. Important IgE-reactivity relationships within several groups of allergen preparations are identified including well-known groups of clinically relevant cross-reactivities

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Abundance and Functional Roles of Intrinsic Disorder in Allergenic Proteins and Allergen Representative Peptides

The pathological process of allergies generally involves an initial activation of certain immune cells, tied to an ensuing inflammatory reaction on renewed contact with the allergen. In IgE-mediated hypersensitivity, this typically occurs in response to otherwise harmless food- or air-borne proteins. As some members of certain protein families carry special properties that make them allergenic, exploring protein allergens at the molecular level is instrumental to an improved understanding of the disease mechanisms, including the identification of relevant antigen features. For this purpose, we inspected a previously identified set of allergen representative peptides (ARPs) to scrutinize protein intrinsic disorder. The resulting study presented here focused on the association between these ARPs and protein intrinsic disorder. In addition, the connection between the disorder-enriched ARPs and UniProt functional keywords was considered. Our analysis revealed that ∼ 20% of the allergen peptides are highly disordered, and that ∼ 77% of ARPs are either located within disordered regions of corresponding allergenic proteins or show more disorder/flexibility than their neighbor regions. Furthermore, among the subset of allergenic proteins, ∼ 70% of the predicted molecular recognition features (MoRFs that consist of short interactive disordered regions undergoing disorder-to-order transitions at interaction with binding partners) were identified as ARPs. These results suggest that intrinsic disorder and MoRFs may play functional roles in IgE-mediated allergy. Proteins 2011; © 2011 Wiley-Liss, Inc

Assessing Relative Bioactivity of Chemical Substances Using Quantitative Molecular Network Topology Analysis

Structurally different chemical substances may cause similar systemic effects in mammalian cells. It is therefore necessary to go beyond structural comparisons to quantify similarity in terms of their bioactivities. In this work, we introduce a generic methodology to achieve this on the basis of Network Biology principles and using publicly available molecular network topology information. An implementation of this method, denoted QuantMap, is outlined and applied to antidiabetic drugs, NSAIDs, 17β-estradiol, and 12 substances known to disrupt estrogenic pathways. The similarity of any pair of compounds is derived from topological comparison of intracellular protein networks, directly and indirectly associated with the respective query chemicals, via a straightforward pairwise comparison of ranked proteins. Although output derived from straightforward chemical/structural similarity analysis provided some guidance on bioactivity, QuantMap produced substance interrelationships that align well with reports on their respective perturbation properties. We believe that QuantMap has potential to provide substantial assistance to drug repositioning, pharmacology evaluation, and toxicology risk assessment

Children living with HIV in Europe: do migrants have worse treatment outcomes?

International audienceTo assess the effect of migrant status on treatment outcomes among children living with HIV in Europe