Serum IgE Reactivity Profiling in an Asthma Affected Cohort

BACKGROUND: Epidemiological evidence indicates that atopic asthma correlates with high serum IgE levels though the contribution of allergen specific IgE to the pathogenesis and the severity of the disease is still unclear. METHODS: We developed a microarray immunoassay containing 103 allergens to study the IgE reactivity profiles of 485 asthmatic and 342 non-asthmatic individuals belonging to families whose members have a documented history of asthma and atopy. We employed k-means clustering, to investigate whether a particular IgE reactivity profile correlated with asthma and other atopic conditions such as rhinitis, conjunctivitis and eczema. RESULTS: Both case-control and parent-to-siblings analyses demonstrated that while the presence of specific IgE against individual allergens correlated poorly with pathological conditions, particular reactivity profiles were significantly associated with asthma (p<10E-09). An artificial neural network (ANN)-based algorithm, calibrated with the profile reactivity data, correctly classified as asthmatic or non-asthmatic 78% of the individual examined. Multivariate statistical analysis demonstrated that the familiar relationships of the study population did not affect the observed correlations. CONCLUSIONS: These findings indicate that asthma is a higher-order phenomenon related to patterns of IgE reactivity rather than to single antibody reactions. This notion sheds new light on the pathogenesis of the disease and can be readily employed to distinguish asthmatic and non-asthmatic individuals on the basis of their serum reactivity profile

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

MC1R variants in childhood and adolescent melanoma: a retrospective pooled analysis of a multicentre cohort.

BACKGROUND: Germline variants in the melanocortin 1 receptor gene (MC1R) might increase the risk of childhood and adolescent melanoma, but a clear conclusion is challenging because of the low number of studies and cases. We assessed the association of MC1R variants with childhood and adolescent melanoma in a large study comparing the prevalence of MC1R variants in child or adolescent patients with melanoma to that in adult patients with melanoma and in healthy adult controls. METHODS: In this retrospective pooled analysis, we used the M-SKIP Project, the Italian Melanoma Intergroup, and other European groups (with participants from Australia, Canada, France, Greece, Italy, the Netherlands, Serbia, Spain, Sweden, Turkey, and the USA) to assemble an international multicentre cohort. We gathered phenotypic and genetic data from children or adolescents diagnosed with sporadic single-primary cutaneous melanoma at age 20 years or younger, adult patients with sporadic single-primary cutaneous melanoma diagnosed at age 35 years or older, and healthy adult individuals as controls. We calculated odds ratios (ORs) for childhood and adolescent melanoma associated with MC1R variants by multivariable logistic regression. Subgroup analysis was done for children aged 18 or younger and 14 years or younger. FINDINGS: We analysed data from 233 young patients, 932 adult patients, and 932 healthy adult controls. Children and adolescents had higher odds of carrying MC1R r variants than did adult patients (OR 1·54, 95% CI 1·02-2·33), including when analysis was restricted to patients aged 18 years or younger (1·80, 1·06-3·07). All investigated variants, except Arg160Trp, tended, to varying degrees, to have higher frequencies in young patients than in adult patients, with significantly higher frequencies found for Val60Leu (OR 1·60, 95% CI 1·05-2·44; p=0·04) and Asp294His (2·15, 1·05-4·40; p=0·04). Compared with those of healthy controls, young patients with melanoma had significantly higher frequencies of any MC1R variants. INTERPRETATION: Our pooled analysis of MC1R genetic data of young patients with melanoma showed that MC1R r variants were more prevalent in childhood and adolescent melanoma than in adult melanoma, especially in patients aged 18 years or younger. Our findings support the role of MC1R in childhood and adolescent melanoma susceptibility, with a potential clinical relevance for developing early melanoma detection and preventive strategies. FUNDING: SPD-Pilot/Project-Award-2015; AIRC-MFAG-11831

Pollination and selection on an introduced island plant

Raw data (floral trait measurements, pollinator measurements, pollinator visits

Data from: A hurricane alters pollinator relationships and natural selection on an introduced island plant

Novel relationships between the floral morphology of introduced plants and the trophic morphology of native pollinators have been hypothesized to cause strong natural selection on both parties, but evidence for such selection is rare. We capitalized on a natural disturbance to examine selection on an introduced plant, Heliconia wagneriana, on the island of Dominica, before and after Hurricane Maria. Prior to the hurricane, female Anthracothorax jugularis hummingbirds, which have longer bills than males, were the main visitor to H. wagneriana, and directional selection on corolla length was insignificant. After the hurricane, shorter-billed male A. jugularis were the main visitor to H. wagneriana. The absence of trait-matching between a short-billed pollinator and a long-flowered plant resulted in directional selection for shorter flowers because males preferentially visited plants with shorter flowers. The amount of nectar removed by male A. jugularis was negatively associated with flower length, with flowers > 53 mm containing nearly five times the nectar than flowers < 53 mm. We estimate a roughly 75% decrease in the population size of A. jugularis, and results suggest the heaviest mortality occurred among short-billed male hummingbirds and larger-bodied individuals of both sexes, which would have higher nectar requirements and the most difficulty obtaining nectar. Our results indicate that hurricanes may alter relationships between plants and pollinators, and that lack of trait-matching resulting from such disturbances may lead to selection on both plant and pollinator

Data from: Bees go up, flowers go down: Increased resource limitation from late spring to summer in agricultural landscapes

&lt;p&gt;Data underlying the publication "Bees go up, flowers go down: Increased resource limitation from late spring to summer in agricultural landscapes". Site coordinates are excluded from this dataset for data protection.&lt;/p&gt;Additional funding was received from the Dutch Minitry of Agriculture, Nature Conservation and Food Quality (BO-43-011.06-007), farmers collective Natuurrijk Limburg, the province of Limburg, and Syngenta. This dataset reflects only the views of the authors. The funding sources had no role in the completion of the study or the creation of the dataset and are not responsible for any use that may be made of the information this dataset contains