Multimedia Vocabularies on the Semantic Web

This document gives an overview on the state-of-the-art of multimedia metadata formats. Initially, practical relevant vocabularies for developers of Semantic Web applications are listed according to their modality scope. In the second part of this document, the focus is set on the integration of the multimedia vocabularies into the Semantic Web, that is to say, formal representations of the vocabularies are discussed

A genome-wide DNA methylation signature for SETD1B-related syndrome

SETD1B is a component of a histone methyltransferase complex that specifically methylates Lys-4 of histone H3 (H3K4) and is responsible for the epigenetic control of chromatin structure and gene expression. De novo microdeletions encompassing this gene as well as de novo missense mutations were previously linked to syndromic intellectual disability (ID). Here, we identify a specific hypermethylation signature associated with loss of function mutations in the SETD1B gene which may be used as an epigenetic marker supporting the diagnosis of syndromic SETD1B-related diseases. We demonstrate the clinical utility of this unique epi-signature by reclassifying previously identified SETD1B VUS (variant of uncertain significance) in two patients

A genome-wide DNA methylation signature for SETD1B-related syndrome

SETD1B is a component of a histone methyltransferase complex that specifically methylates Lys-4 of histone H3 (H3K4) and is responsible for the epigenetic control of chromatin structure and gene expression. De novo microdeletions encompassing this gene as well as de novo missense mutations were previously linked to syndromic intellectual disability (ID). Here, we identify a specific hypermethylation signature associated with loss of function mutations in the SETD1B gene which may be used as an epigenetic marker supporting the diagnosis of syndromic SETD1B-related diseases. We demonstrate the clinical utility of this unique epi-signature by reclassifying previously identified SETD1B VUS (variant of uncertain significance) in two patients

Genetic Analyses in Small for Gestational Age Newborns

Context: Small for gestational age (SGA) can be a result of fetal growth restriction, associated with perinatal morbidity and mortality. Mechanisms that control prenatal growth are poorly understood. Objective: The aim of the present study was to gain more insight into prenatal growth failure and determine an effective diagnostic approach in SGA newborns. We hypothesized that one or more CNVs and disturbed methylation and sequence variants may be present in genes known to be associated with fetal growth. Design: A prospective cohort study of subjects with a low birthweight for gestational age. Setting: The study was conducted at an academic pediatric research institute. Patients: A total of 21 SGA newborns with a mean birthweight below the 1st centile and a control cohort of 24 appropriate for gestational age newborns were studied. Intervention: Array comparative genomic hybridization, genome-wide methylation studies and exome sequencing were performed. Main Outcome Measures The numbers of copy number variations, methylation disturbances and sequence variants. Results: The genetic analyses demonstrated three CNVs, one systematically disturbed methylation pattern and one sequence variant explaining the SGA. Additional methylation disturbances and sequence variants were present 20 patients. In 19 patients, multiple abnormalities were found. Conclusion: Our results confirm the influence of a large number of mechanisms explaining dysregulation of fetal growth. We conclude that copy number variations, methylation disturbances and sequence variants all contribute to prenatal growth failure. Such genetic workup can be an effective diagnostic approach in SGA newborns

Correction: Clinical epigenomics: genome-wide DNA methylation analysis for the diagnosis of Mendelian disorders (Genetics in Medicine, (2021), 23, 6, (1065-1074), 10.1038/s41436-020-01096-4)

A Correction to this paper has been published: https://doi.org/10.1038/s41436-021-01130-z