MRD4U: A path to development for personalized liquid biopsy for children with central nervous system tumors.

Background: Liquid biopsy assays using cerebrospinal fluid (CSF) can revolutionize care for children with central nervous system (CNS) tumors by enabling precise monitoring of therapeutic responses and detecting recurrence or measurable residual disease (MRD). These assays can detect cell-free, circulating tumor DNA (ctDNA) via somatic alterations, though accurately measuring low-abundance ctDNA in CSF is challenging.

Methods: Our research focused on the optimization of next-generation sequencing library preparation from cell-free DNA (cfDNA), evaluating four commercial kits to address the low nucleic acid yield in CSF-derived cfDNA.

CAVaLRi: An Algorithm for Rapid Identification of Diagnostic Germline Variation.

Clinical exome and genome sequencing (ES/GS) have become indispensable diagnostic tools for rare genetic diseases (RGD). However, the interpretation of ES/GS presents a substantial operational challenge in clinical settings. Test interpretation requires the review of hundreds of genetic variants, a task that has become increasingly challenging given the rising use of ES/GS.

Novel pathogenic GATA6 variant associated with congenital heart disease, diabetes mellitus and necrotizing enterocolitis.

Background: Pathogenic GATA6 variants have been associated with congenital heart disease (CHD) and a spectrum of extracardiac abnormalities, including pancreatic agenesis, congenital diaphragmatic hernia, and developmental delay. However, the comprehensive genotype-phenotype correlation of pathogenic GATA6 variation in humans remains to be fully understood.

Methods: Exome sequencing was performed in a family where four members had CHD.

Comparative genomics and phenotypic studies to determine site-specificity of in the lower gastrointestinal tract of humans.

() is an important commensal in the human gut; however, it is unknown whether strains show site-specificity in the lower gut. To investigate this, we assessed genotypic and phenotypic differences in 37 clone pairs (two strains with very similar multiple locus variable-number-tandem-repeat analysis [MLVA] profiles) of isolated from mucosal biopsies of two different gut locations (terminal ileum and rectum). The clone pairs varied at the genomic level; single nucleotide polymorphisms (SNPs) were common, multiple nucleotide polymorphisms (MNPs) were observed but less common, and few indels (insertions and deletions) were detected.

Exome sequencing in multiplex families with left-sided cardiac defects has high yield for disease gene discovery.

Congenital heart disease (CHD) is a common group of birth defects with a strong genetic contribution to their etiology, but historically the diagnostic yield from exome studies of isolated CHD has been low. Pleiotropy, variable expressivity, and the difficulty of accurately phenotyping newborns contribute to this problem. We hypothesized that performing exome sequencing on selected individuals in families with multiple members affected by left-sided CHD, then filtering variants by population frequency, in silico predictive algorithms, and phenotypic annotations from publicly available databases would increase this yield and generate a list of candidate disease-causing variants that would show a high validation rate.

Molecular and metabolic characteristics of wastewater associated Escherichia coli strains.

We previously characterized the genetic diversity of Escherichia coli strains isolated from septic tanks in the Canberra region, Australia. In this study, we used repetitive element palindromic (REP) PCR fingerprinting to identify dominant REP-types belonging to phylogroups A and B1 strains across septic tanks. Subsequently, 76 E.

Use of machine learning to classify high-risk variants of uncertain significance in lamin A/C cardiac disease.

Background: Variation in lamin A/C results in a spectrum of clinical disease, including arrhythmias and cardiomyopathy. Benign variation is rare, and classification of LMNA missense variants via in silico prediction tools results in a high rate of variants of uncertain significance (VUSs).

Objective: The goal of this study was to use a machine learning (ML) approach for in silico prediction of LMNA pathogenic variation.

Prevalence, diversity and genetic structure of Escherichia coli isolates from septic tanks.

The present study investigated the diversity and genetic structure of Escherichia coli isolates from 100 septic tanks in the Canberra region, Australia. The physicochemical characteristics of the septic tanks were determined to examine the extent to which environmental factors might influence E. coli prevalence, diversity and population structure.

Maternal mosaicism for a missense variant in the gene that causes Snyder-Robinson syndrome.

There is increasing recognition for the contribution of genetic mosaicism to human disease, particularly as high-throughput sequencing has enabled detection of sequence variants at very low allele frequencies. Here, we describe an infant male who presented at 9 mo of age with hypotonia, dysmorphic features, congenital heart disease, hyperinsulinemic hypoglycemia, hypothyroidism, and bilateral sensorineural hearing loss. Whole-genome sequencing of the proband and the parents uncovered an apparent de novo mutation in the X-linked gene.

The E phylogroup of Escherichia coli is highly diverse and mimics the whole E. coli species population structure.

To get a global picture of the population structure of the Escherichia coli phylogroup E, encompassing the O157:H7 EHEC lineage, we analysed the whole genome of 144 strains isolated from various continents, hosts and lifestyles and representative of the phylogroup diversity. The strains possess 4331 to 5440 genes with a core genome of 2771 genes and a pangenome of 33 722 genes. The distribution of these genes among the strains shows an asymmetric U-shaped distribution.

Synonymous variants that disrupt messenger RNA structure are significantly constrained in the human population.

Background: The role of synonymous single-nucleotide variants in human health and disease is poorly understood, yet evidence suggests that this class of "silent" genetic variation plays multiple regulatory roles in both transcription and translation. One mechanism by which synonymous codons direct and modulate the translational process is through alteration of the elaborate structure formed by single-stranded mRNA molecules. While tools to computationally predict the effect of non-synonymous variants on protein structure are plentiful, analogous tools to systematically assess how synonymous variants might disrupt mRNA structure are lacking.

Genomic analysis of phylogenetic group B2 extraintestinal pathogenic E. coli causing infections in dogs in Australia.

This study investigated the prevalence of extraintestinal pathogenic E. coli (ExPEC)-associated sequence types (STs) from phylogenetic group B2 among 449 fluoroquinolone-susceptible dog clinical isolates from Australia. Isolates underwent PCR-based phylotyping and random amplified polymorphic DNA analysis to determine clonal relatedness.

Phenotypic characteristics contributing to the enhanced growth of Escherichia coli bloom strains.

During bloom events, Escherichia coli cell counts increase to between 10,000 and 100,000 cfu/100 ml of water. The strains responsible for bloom events belong to E. coli phylogenetic groups A and B1, and all have acquired a capsule from Klebsiella.

Genetic structure, antimicrobial resistance and frequency of human associated Escherichia coli sequence types among faecal isolates from healthy dogs and cats living in Canberra, Australia.

Extraintestinal pathogenic Escherichia coli (ExPEC) cause clinical infections in humans. Understanding the evolution and dissemination of ExPEC strains via potential reservoirs is important due to associated morbidity, health care costs and mortality. To further understanding this survey has examined isolates recovered from the faeces of 221 healthy dogs and 427 healthy cats.

Diversity and distribution of Klebsiella capsules in Escherichia coli.

E. coli strains responsible for elevated counts (blooms) in freshwater reservoirs in Australia carry a capsule originating from Klebsiella. The occurrence of Klebsiella capsules in E.

Dissemination and persistence of extended-spectrum cephalosporin-resistance encoding IncI1-bla plasmid among Escherichia coli in pigs.

This study investigated the ecology, epidemiology and plasmid characteristics of extended-spectrum cephalosporin (ESC)-resistant E. coli in healthy pigs over a period of 4 years (2013-2016) following the withdrawal of ESCs. High carriage rates of ESC-resistant E.

Factors affecting the presence, genetic diversity and antimicrobial sensitivity of Escherichia coli in poultry meat samples collected from Canberra, Australia.

To investigate the factors determining the clonal composition of Escherichia coli in poultry meat samples, 306 samples were collected from 16 shops, representing three supermarket chains and an independent butchery located in each of the four town centers of Canberra, Australia, during the summer, autumn and winter. A total of 3415 E. coli isolates were recovered and assigned to a phylogenetic group using the Clermont quadruplex PCR method, fingerprinted using repetitive element palindromic (REP) PCR and screened for their antimicrobial susceptibility profiles.

Within-host evolution versus immigration as a determinant of Escherichia coli diversity in the human gastrointestinal tract.

When a human host harbors two or more strains of Escherichia coli, the second strain is more likely to be a member of the same phylogroup rather than a different phylogroup. This outcome may be the consequence of a within host evolution event or an independent immigration/establishment event. To determine the relative importance of these two events in determining E.

AR-13, a Celecoxib Derivative, Directly Kills and Aids Clearance and Mouse Survival .

() is the causative agent of tularemia and is classified as a Tier 1 select agent. No licensed vaccine is currently available in the United States and treatment of tularemia is confined to few antibiotics. In this study, we demonstrate that AR-13, a derivative of the cyclooxygenase-2 inhibitor celecoxib, exhibits direct bactericidal killing activity against including a type A strain of (SchuS4) and the live vaccine strain (LVS), as well as toward the intracellular proliferation of LVS in macrophages, without causing significant host cell toxicity.

Fine-Scale Structure Analysis Shows Epidemic Patterns of Clonal Complex 95, a Cosmopolitan Lineage Responsible for Extraintestinal Infection.

The lineage known as clonal complex 95 (CC95) is a cosmopolitan human-associated lineage responsible for a significant fraction of extraintestinal infections of humans. Whole-genome sequence data of 200 CC95 strains from various origins enabled determination of the CC95 pangenome. The pangenome analysis revealed that strains of the complex could be assigned to one of five subgroups that vary in their serotype, extraintestinal virulence, virulence gene content, and antibiotic resistance gene profile.

Bilateral Orbital Pseudotumor in a 3-Year-Old Child: A Case Report.

Orbital pseudotumor is a rare, idiopathic, inflammatory process within the orbit. Early diagnosis is essential to prevent corneal, retinal and extraocular muscle damage. This article describes the presentation and clinical course of a 3-year-old male with bilateral orbital pseudotumor.

Genetic Attributes of E. coli Isolates from Chlorinated Drinking Water.

Escherichia coli, is intimately associated with both human health and water sanitation. E. coli isolates from water can either be (i) host associated commensals, indicating recent faecal contamination; (ii) diarrheal pathogens or (iii) extra-intestinal pathogens that pose a direct health risk; or (iv) free-living.