Natural killer cell subpopulations in the peripheral blood of single ventricle/hypoplastic left heart syndrome patients via single-cell RNA sequencing.

Natural Killer (NK) cells are integral components of the innate immune system, recognizing and eliminating virus-infected cells. They may play a crucial role in the immune response and contribute to the complications associated with Single Ventricle/Hypoplastic Left Heart Syndrome (SV/HLHS). Utilizing single-cell RNA sequencing (scRNA-seq), NK cells from peripheral blood mononuclear cells (PBMCs) were analyzed in three de-identified SV/HLHS cases and three healthy controls.

Single-Cell RNA Sequencing of Peripheral Blood Mononuclear Cells in Patients With Single Ventricle/Hypoplastic Left Heart Syndrome.

Background: Single ventricle and hypoplastic left heart syndrome (SV/HLHS) has detrimental effects on multiple organ systems, including peripheral blood mononuclear cells (PBMCs), and can weaken the immune system, exacerbating the risk of infection and various cardiovascular complications.

Methods: Using single-cell RNA sequencing (scRNA-seq), we studied PBMCs from 33 pediatric patients (10 females and 23 males) with SV/HLHS. By a pair-wide study design, the SV/HLHS patients were compared to 33 controls without heart disease.

Clinical association between asthma and anxiety is unrelated to genetic risk factors.

Although asthma and anxiety are clinically associated, the genetic basis of their co-occurrence has not been established. This study investigates whether the two conditions share underlying genetic risk factors, providing a foundation for understanding their biological interplay. Pediatric patients diagnosed with anxiety or asthma (n = 2168; 1085 females and 1083 males) were compared to controls without either condition (n = 1960; 926 females and 1034 males).

Deep learning algorithms reveal genomic markers for anxiety disorder in a large cohort of children with down syndrome.

Despite a significant burden of neurobehavioral and psychiatric comorbidities in children with Down syndrome (DS), and the general increased risk for anxiety in individuals with intellectual disabilities (ID), children with DS have significantly lower odds of anxiety. Understanding the specific mechanisms of anxiety in DS could inform the development of new treatments. This study performed a comprehensive investigation of genomic variants that contribute to anxiety disorders in DS, as well as variants shared in other mental disorders.

VCL/ICAM-1 pathway is associated with lung inflammatory damage in SARS-CoV-2 Omicron infection.

SARS-CoV-2 variants present diverse clinical manifestations, necessitating deeper insights into their pathogenic effects. This study employs multi-omics approaches to investigate the molecular mechanisms underlying SARS-CoV-2 infection, focusing on vascular damage. Plasma proteomic analysis of unvaccinated participants infected with Omicron BA.

Risk of Alzheimer's disease in Down syndrome: Insights gained by multi-omics.

Individuals with Down syndrome (DS) are highly susceptible to Alzheimer's disease (AD). The integration of genomics, transcriptomics, epigenomics, proteomics, and metabolomics enables unprecedented understanding of DS-AD, offering a detailed picture of this complex issue. The vast -omics data also present challenges that reflect the complexity of genetic information flow.

Rare variants in cardiomyopathy genes predispose to cardiac injury in severe COVID-19 patients of African or Hispanic ancestry.

In one of the earliest reports from China during COVID-19, it was noted that over 20% of patients hospitalized with the disease had significant elevations of troponin, a marker of myocardial tissue damage, that put them at a higher risk. In a hypothesis-independent whole exome sequencing (WES) study in hospitalized COVID-19 patients of diverse ancestry, we observed putative enrichment in pathogenic variants in genes known to be involved in the pathogenesis of cardiomyopathy. This observation led us to hypothesize that the observed high morbidity and mortality in these patients might be due to the presence of rare genetic factors that had previously been silent but became relevant as a consequence of the severe stress inflicted by an infection with SARS-CoV-2.

Genetic Association of Juvenile Idiopathic Arthritis With Adult Rheumatic Disease.

Importance: Patients with juvenile idiopathic arthritis (JIA) may develop adult rheumatic diseases later in life, and prolonged or recurrent disease activity is often associated with substantial disability; therefore, it is important to identify patients with JIA at high risk of developing adult rheumatic diseases and provide specialized attention and preventive care to them.

Objective: To elucidate the full extent of the genetic association of JIA with adult rheumatic diseases, to improve treatment strategies and patient outcomes for patients at high risk of developing long-term rheumatic diseases.

Design, Setting, And Participants: In this genetic association study of 4 disease genome-wide association study (GWAS) cohorts from 2013 to 2024 (JIA, rheumatoid arthritis [RA], systemic lupus erythematosus [SLE], and systemic sclerosis [SSc]), patients in the JIA cohort were recruited from the US, Australia, and Norway (with a UK cohort included in the meta-analyzed cohort), while patients in the other 3 cohorts were recruited from US and Western European countries.

The Role of BAG3 Protein Interactions in Cardiomyopathies.

Bcl-2-associated athanogene 3 (BAG3) plays an important function in cellular protein quality control (PQC) maintaining proteome stability. Mutations in the gene result in cardiomyopathies. Due to its roles in cardiomyopathies and the complexity of BAG3-protein interactions, it is important to understand these protein interactions given the importance of the multifunctional cochaperone BAG3 in cardiomyocytes, using an in vitro cardiomyocyte model.

Navigating Complexity in Postural Orthostatic Tachycardia Syndrome.

Postural Orthostatic Tachycardia Syndrome (POTS) affects up to 1% of the US population, predominantly women, and is characterized by a complex, elusive etiology and heterogeneous phenotypes. This review delves into the intricate physiology and etiology of POTS, decoding the roles of the sinoatrial node, the autonomic nervous system, fluid dynamics, and the interplay between the immune and endocrine systems. It further examines key contributing factors such as dysautonomia, thoracic hypovolemia, autonomic neuropathies, sympathetic denervation, autoimmune responses, and associations with conditions such as small-fiber neuropathy and mast cell activation syndrome.

Copy number variations contribute to malignant tumor development in children with serious birth defects.

There are two key signatures of pediatric cancers: (a) higher prevalence of germline alterations and (b) heterogeneity in alteration types. Recent population-based assessments have demonstrated that children with birth defects (BDs) are more likely to develop cancer even without chromosomal anomalies; therefore, explorations of genetic alterations in children with BDs and cancers could provide new insights into the underlying mechanisms for pediatric tumor development. We performed whole-genome sequencing (WGS) on blood-derived DNA for 1556 individuals without chromosomal anomalies, including 454 BD probands with at least one type of malignant tumor, 757 cancer-free children with BDs, and 345 healthy individuals, focusing on copy number variation (CNV) analysis.

Single-Cell Omics for Transcriptome CHaracterization (SCOTCH): isoform-level characterization of gene expression through long-read single-cell RNA sequencing.

Recent development involving long-read single-cell transcriptome sequencing (lr-scRNA-Seq) represents a significant leap forward in single-cell genomics. With the recent introduction of R10 flowcells by Oxford Nanopore, we propose that previous computational methods designed to handle high sequencing error rates are less relevant, and that the traditional approach using short reads to compile "barcode space" (candidate barcode list) to de-multiplex long reads are no longer necessary. Instead, computational methods should now shift focus on harnessing the unique benefits of long reads to analyze transcriptome complexity.

Shared molecular mechanisms and transdiagnostic potential of neurodevelopmental disorders and immune disorders.

The co-occurrence and familial clustering of neurodevelopmental disorders and immune disorders suggest shared genetic risk factors. Based on genome-wide association summary statistics from five neurodevelopmental disorders and four immune disorders, we conducted genome-wide, local genetic correlation and polygenic overlap analysis. We further performed a cross-trait GWAS meta-analysis.

gene contributes to autism by epigenetic dysregulation of neural and immune pathways.

Background: Epigenetics makes substantial contribution to the aetiology of autism spectrum disorder (ASD) and may harbour a unique opportunity to prevent the development of ASD. We aimed to identify novel epigenetic genes involved in ASD aetiology.

Methods: Trio-based whole exome sequencing was conducted on ASD families.

CRISPR/Cas9 screenings unearth protein arginine methyltransferase 7 as a novel essential gene in prostate cancer metastasis.

Due to the limited effectiveness of current treatments, the survival rate of patients with metastatic castration-resistant prostate cancer (mCRPC) is significantly reduced. Consequently, it is imperative to identify novel therapeutic targets for managing these patients. Since the invasive ability of cells is crucial for establishing and maintaining metastasis, the aim of this study was to identify the essential regulators of invasive abilities of mCRPC cells by conducting two independent high-throughput CRISPR/Cas9 screenings.

Revealing novel genomic insights and therapeutic targets for juvenile idiopathic arthritis through omics.

Background: The genetic architecture of JIA remains only partially comprehended. There is a clear imperative for continued endeavours to uncover insights into the underlying causes of JIA.

Methods: This study encompassed a comprehensive spectrum of endeavours, including conducting a JIA genome-wide association study (GWAS) meta-analysis that incorporated data from 4550 JIA cases and 18 446 controls.

Target genes regulated by CLEC16A intronic region associated with common variable immunodeficiency.

Background: CLEC16A intron 19 has been identified as a candidate locus for common variable immunodeficiency (CVID).

Objectives: This study sought to elucidate the molecular mechanism by which variants at the CLEC16A intronic locus may contribute to the pathogenesis of CVID.

Methods: The investigators performed fine-mapping of the CLEC16A locus in a CVID cohort, then deleted the candidate functional SNP in T-cell lines by the CRISPR-Cas9 technique and conducted RNA-sequencing to identify target gene(s).

Mitochondrial DNA Haplogroup K Is Protective Against Autism Spectrum Disorder Risk in Populations of European Ancestry.

Objective: Accumulative evidence indicates a critical role of mitochondrial function in autism spectrum disorders (ASD), implying that ASD risk may be linked to mitochondrial dysfunction due to DNA (mtDNA) variations. Although a few studies have explored the association between mtDNA variations and ASD, the role of mtDNA in ASD is still unclear. Here, we aimed to investigate whether mitochondrial DNA haplogroups are associated with the risk of ASD.

High Comorbidity of Pediatric Cancers in Patients with Birth Defects: Insights from Whole Genome Sequencing Analysis of Copy Number Variations.

Background: Patients with birth defects (BD) exhibit an elevated risk of cancer. We aimed to investigate the potential link between pediatric cancers and BDs, exploring the hypothesis of shared genetic defects contributing to the coexistence of these conditions.

Methods: This study included 1454 probands with BDs (704 females and 750 males), including 619 (42.