Supplementary Material for: Epitope-Specific IgE at 1 Year of Age Can Predict Peanut Allergy Status at 5 Years

Background: Currently, there is no laboratory test that can accurately identify children at risk of developing peanut allergy. Utilizing a subset of children randomized to the peanut avoidance arm of the LEAP trial, we monitored the development of epitope-specific (ses-)IgE and ses-IgG4 from 4–11 months to 5 years of age. Objective: The aim of the study was to evaluate the prognostic ability of epitope-specific antibodies to predict the result of an oral food challenge (OFC) at 5 years. Methods: A Bead-Based Epitope Assay was used to quantitate IgE and IgG4 to 64 sequential (linear) epitopes from Ara h 1–3 proteins at 4–11 months, 1 and 2.5 years of age in 74 subjects (38 of them with a positive OFC at 5 years). Specific IgE (sIgE) to peanut and component proteins was measured using ImmunoCAP. Machine learning methods were used to identify the earliest time point to predict 5-year outcome, developing prognostic algorithms based only on 4–11 month samples, 1-year or 2.5-year, and a combination of them. Data from 74 children were iteratively split 3:1 into training and validation sets, and machine learning models were developed to predict the 5-year outcome. A test set (n = 90) from an independent cohort was used for final evaluation. Results: Elastic-Net algorithm combining ses-IgE and IgE to Ara h 1, 2, 3, and 9 proteins could predict the 5-year peanut allergy status of LEAP participants with an average validation accuracy of 64% at baseline. Samples taken at 1 year accurately predicted a 5-year OFC outcome with 83% accuracy. This performance remained consistent when evaluated on an independent CoFAR2 cohort with an accuracy of 78% for the 1-year model. Conclusion: IgE antibody profiles at 1 year of age are predictive of peanut OFC at 5 years in children avoiding peanuts. If further confirmed, this model may enable early identification of infants who may benefit from early immunotherapeutic interventions

FuntooNorm: An R package for normalization of DNA methylation data when there are multiple cell or tissue types

Development Psychopathology in context: famil

funtooNorm: an R package for normalization of DNA methylation data when there are multiple cell or tissue types

Motivation: DNA methylation patterns are well known to vary substantially across cell types or tissues. Hence, existing normalization methods may not be optimal if they do not take this into account. We therefore present a new R package for normalization of data from the Illumina Infinium Human Methylation450 BeadChip (Illumina 450 K) built on the concepts in the recently published funNorm method, and introducing cell-type or tissue-type flexibility. Results: funtooNorm is relevant for data sets containing samples from two or more cell or tissue types. A visual display of cross-validated errors informs the choice of the optimal number of components in the normalization. Benefits of cell (tissue)-specific normalization are demonstrated in three data sets. Improvement can be substantial; it is strikingly better on chromosome X, where methylation patterns have unique inter-tissue variability. Availability and Implementation: An R package is available at https://github.com/GreenwoodLab/funtooNorm, and has been submitted to Bioconductor at http://bioconductor.org. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online