Systems biology dissection of PTSD and MDD across brain regions, cell types, and blood.

The molecular pathology of stress-related disorders remains elusive. Our brain multiregion, multiomic study of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) included the central nucleus of the amygdala, hippocampal dentate gyrus, and medial prefrontal cortex (mPFC). Genes and exons within the mPFC carried most disease signals replicated across two independent cohorts.

Exome sequencing implicates ancestry-related Mendelian variation at SYNE1 in childhood-onset essential hypertension.

Childhood-onset essential hypertension (COEH) is an uncommon form of hypertension that manifests in childhood or adolescence and, in the United States, disproportionately affects children of African ancestry. The etiology of COEH is unknown, but its childhood onset, low prevalence, high heritability, and skewed ancestral demography suggest the potential to identify rare genetic variation segregating in a Mendelian manner among affected individuals and thereby implicate genes important to disease pathogenesis. However, no COEH genes have been reported to date.

A first-generation genome-wide map of correlated DNA methylation demonstrates highly coordinated and tissue-independent clustering across regulatory regions.

Genome-wide DNA methylation studies have typically focused on quantitative assessments of CpG methylation at individual loci. Although methylation states at nearby CpG sites are known to be highly correlated, suggestive of an underlying coordinated regulatory network, the extent and consistency of inter-CpG methylation correlation across the genome, including variation between individuals, disease states, and tissues, remains unknown. Here, we leverage image conversion of correlation matrices to identify correlated methylation units (CMUs) across the genome, describe their variation across tissues, and annotate their regulatory potential using 35 public Illumina BeadChip datasets spanning more than 12,000 individuals and 26 different tissues.

SRCP: a comprehensive pipeline for accurate annotation and quantification of circRNAs.

Here we describe a new integrative approach for accurate annotation and quantification of circRNAs named Short Read circRNA Pipeline (SRCP). Our strategy involves two steps: annotation of validated circRNAs followed by a quantification step. We show that SRCP is more sensitive than other individual pipelines and allows for more comprehensive quantification of a larger number of differentially expressed circRNAs.

Edematous severe acute malnutrition is characterized by hypomethylation of DNA.

Edematous severe acute childhood malnutrition (edematous SAM or ESAM), which includes kwashiorkor, presents with more overt multi-organ dysfunction than non-edematous SAM (NESAM). Reduced concentrations and methyl-flux of methionine in 1-carbon metabolism have been reported in acute, but not recovered, ESAM, suggesting downstream DNA methylation changes could be relevant to differences in SAM pathogenesis. Here, we assess genome-wide DNA methylation in buccal cells of 309 SAM children using the 450 K microarray.

NovoGraph: Human genome graph construction from multiple long-read assemblies.

Genome graphs are emerging as an important novel approach to the analysis of high-throughput human sequencing data. By explicitly representing genetic variants and alternative haplotypes in a mappable data structure, they can enable the improved analysis of structurally variable and hyperpolymorphic regions of the genome. In most existing approaches, graphs are constructed from variant call sets derived from short-read sequencing.

Patient-Specific Quantitation of Mitral Valve Strain by Computer Analysis of Three-Dimensional Echocardiography: A Pilot Study.

Background: A paucity of data exists on mitral valve (MV) deformation during the cardiac cycle in man. Real-time 3-dimensional (3D) echocardiography now allows dynamic volumetric imaging of the MV, thus enabling computerized modeling of MV function directly in health and disease.

Methods And Results: MV imaging using 3D transesophageal echocardiography was performed in 10 normal subjects and 10 patients with moderate-to-severe or severe organic mitral regurgitation.