Whole exome-seq and RNA-seq data reveal unique neoantigen profiles in Kenyan breast cancer patients.

Background: The immune response against tumors relies on distinguishing between self and non-self, the basis of cancer immunotherapy. Neoantigens from somatic mutations are central to many immunotherapeutic strategies and understanding their landscape in breast cancer is crucial for targeted interventions. We aimed to profile neoantigens in Kenyan breast cancer patients using genomic DNA and total RNA from paired tumor and adjacent non-cancerous tissue samples of 23 patients.

Self-assembling SARS-CoV-2 spike-HBsAg nanoparticles elicit potent and durable neutralizing antibody responses via genetic delivery.

While several COVID-19 vaccines have been in use, more effective and durable vaccines are needed to combat the ongoing COVID-19 pandemic. Here, we report highly immunogenic self-assembling SARS-CoV-2 spike-HBsAg nanoparticles displaying a six-proline-stabilized WA1 (wild type, WT) spike S6P on a HBsAg core. These S6P-HBsAgs bound diverse domain-specific SARS-CoV-2 monoclonal antibodies.

Whole Exome Sequencing in a Population With Severe Congenital Anomalies of Kidney and Urinary Tract.

Fetal and neonatal interventions (e.g., amnioinfusions, amniotic shunting, and infant dialysis) have increased survival of infants with severe Congenital Anomalies of the Kidney and Urinary Tract (CAKUT), however, outcomes vary dramatically.

Monoallelic IFT140 pathogenic variants are an important cause of the autosomal dominant polycystic kidney-spectrum phenotype.

Autosomal dominant polycystic kidney disease (ADPKD), characterized by progressive cyst formation/expansion, results in enlarged kidneys and often end stage kidney disease. ADPKD is genetically heterogeneous; PKD1 and PKD2 are the common loci (∼78% and ∼15% of families) and GANAB, DNAJB11, and ALG9 are minor genes. PKD is a ciliary-associated disease, a ciliopathy, and many syndromic ciliopathies have a PKD phenotype.

Programmed Death Ligand 1 Expression and Related Markers in Pleuropulmonary Blastoma.

Introduction: Pleuropulmonary blastoma (PPB), a rare childhood neoplasm of the lung, is linked to pathogenic variants. We investigated checkpoint inhibitor markers including Programmed Death Ligand 1 (PD-L1), PD1, CD8 and tumor mutational burden (TMB) in PPB.

Material And Methods: Cases were collected from departmental archives and the International PPB/ Registry.

Optimizing clinical cytology touch preparations for next generation sequencing.

Intraoperative diagnosis is routinely performed on cytology touch preparations (TPs) from core needle biopsies (CNBs). Current interest promotes their utility as an important source of patient tissue for clinical genomic testing. Herein we present whole genome structural variant analysis (SVA) from mate-pair sequencing (MPseq) and whole exome sequencing (WES) mutation calling in DNA directly whole genome amplified (WGA) from TPs.

Evaluation of esthetic parameters related to a single implant restoration by laypeople and dentists.

Statement Of Problem: Currently available assessment tools for evaluating the esthetic outcome of implant restorations consist of objective indices created for dentists. The investigation of esthetic parameters according to the patient's perspective is lacking.

Purpose: The purpose of this observational study was to evaluate and compare the importance of different soft-tissue and restoration-related esthetic parameters for patients and clinicians.

PKD1 Duplicated regions limit clinical Utility of Whole Exome Sequencing for Genetic Diagnosis of Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited monogenic renal disease characterised by the accumulation of clusters of fluid-filled cysts in the kidneys and is caused by mutations in PKD1 or PKD2 genes. ADPKD genetic diagnosis is complicated by PKD1 pseudogenes located proximal to the original gene with a high degree of homology. The next generation sequencing (NGS) technology including whole exome sequencing (WES) and whole genome sequencing (WGS), is becoming more affordable and its use in the detection of ADPKD mutations for diagnostic and research purposes more widespread.

Lobular Carcinomas Display Intralesion Genetic Heterogeneity and Clonal Evolution in the Progression to Invasive Lobular Carcinoma.

Purpose: Lobular carcinoma (LCIS) is a preinvasive lesion of the breast. We sought to define its genomic landscape, whether intralesion genetic heterogeneity is present in LCIS, and the clonal relatedness between LCIS and invasive breast cancers. We reanalyzed whole-exome sequencing (WES) data and performed a targeted amplicon sequencing validation of mutations identified in 43 LCIS and 27 synchronous more clinically advanced lesions from 24 patients [9 ductal carcinomas (DCIS), 13 invasive lobular carcinomas (ILC), and 5 invasive ductal carcinomas (IDC)].

Characterization of three ciliopathy pedigrees expands the phenotype associated with biallelic C2CD3 variants.

Whole exome sequencing (WES) is utilized in diagnostic odyssey cases to identify the underlying genetic cause associated with complex phenotypes. Recent publications suggest that WES reveals the genetic cause in ~25% of these cases and is most successful when applied to children with neurological disease. The residual 75% of cases remain genetically elusive until more information becomes available in the literature or functional studies are pursued.

Monoallelic Mutations to DNAJB11 Cause Atypical Autosomal-Dominant Polycystic Kidney Disease.

Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by the progressive development of kidney cysts, often resulting in end-stage renal disease (ESRD). This disorder is genetically heterogeneous with ∼7% of families genetically unresolved. We performed whole-exome sequencing (WES) in two multiplex ADPKD-like pedigrees, and we analyzed a further 591 genetically unresolved, phenotypically similar families by targeted next-generation sequencing of 65 candidate genes.

Whole-exome sequencing for mutation detection in pediatric disorders of insulin secretion: Maturity onset diabetes of the young and congenital hyperinsulinism.

Background: To assess the utility of whole-exome sequencing (WES) for mutation detection in maturity-onset diabetes of the young (MODY) and congenital hyperinsulinism (CHI). MODY and CHI are the two commonest monogenic disorders of glucose-regulated insulin secretion in childhood, with 13 causative genes known for MODY and 10 causative genes identified for CHI. The large number of potential genes makes comprehensive screening using traditional methods expensive and time-consuming.

Whole-exome sequencing in amyotrophic lateral sclerosis suggests NEK1 is a risk gene in Chinese.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurological disease characterised by the degeneration of motor neurons, which are responsible for voluntary movement. There remains limited understanding of disease aetiology, with median survival of ALS of three years and no effective treatment. Identifying genes that contribute to ALS susceptibility is an important step towards understanding aetiology.

Exome sequences versus sequential gene testing in the UK highly specialised Service for Limb Girdle Muscular Dystrophy.

Background: Limb girdle muscular dystrophies are a group of rare and genetically heterogeneous diseases that share proximal weakness as a common feature; however they are often lacking very specific phenotypic features to allow an accurate differential diagnosis based on the clinical signs only, limiting the diagnostic rate using phenotype driven genetic testing. Next generation sequencing provides an opportunity to obtain molecular diagnoses for undiagnosed patients, as well as identifying novel genetic causes of muscle diseases. We performed whole exome sequencing (WES) on 104 affected individuals from 75 families in who standard gene by gene testing had not yielded a diagnosis.

Clinical and neuroimaging findings in two brothers with limb girdle muscular dystrophy due to LAMA2 mutations.

Recessive mutations in LAMA2 commonly cause congenital muscular dystrophy (MDC1A) and, rarely, limb girdle muscular dystrophy (LGMD). We report 2 brothers who presented in adulthood with LGMD due to novel mutations in LAMA2 identified by whole exome sequencing (WES). Muscle biopsy more than 30 years ago demonstrated dystrophic changes but was not available for immunoanalysis.

Protein detection by Simple Western™ analysis.

Protein Simple© has taken a well-known protein detection method, the western blot, and revolutionized it. The Simple Western™ system uses capillary electrophoresis to identify and quantitate a protein of interest. Protein Simple© provides multiple detection apparatuses (Wes, Sally Sue, or Peggy Sue) that are suggested to save scientists valuable time by allowing the researcher to prepare the protein sample, load it along with necessary antibodies and substrates, and walk away.

Whole exome sequencing is an efficient, sensitive and specific method for determining the genetic cause of short-rib thoracic dystrophies.

Short-rib thoracic dystrophies (SRTDs) are congenital disorders due to defects in primary cilium function. SRTDs are recessively inherited with mutations identified in 14 genes to date (comprising 398 exons). Conventional mutation detection (usually by iterative Sanger sequencing) is inefficient and expensive, and often not undertaken.

COL1A1 C-propeptide cleavage site mutation causes high bone mass, bone fragility and jaw lesions: a new cause of gnathodiaphyseal dysplasia?

Gnathodiaphyseal dysplasia (GDD) is a rare autosomal dominant condition characterized by bone fragility, irregular bone mineral density (BMD) and fibro-osseous lesions in the skull and jaw. Mutations in Anoctamin-5 (ANO5) have been identified in some cases. We aimed to identify the causative mutation in a family with features of GDD but no mutation in ANO5, using whole exome capture and massive parallel sequencing (WES).

Whole-exome sequencing supports genetic heterogeneity in childhood apraxia of speech.

Background: Childhood apraxia of speech (CAS) is a rare, severe, persistent pediatric motor speech disorder with associated deficits in sensorimotor, cognitive, language, learning and affective processes. Among other neurogenetic origins, CAS is the disorder segregating with a mutation in FOXP2 in a widely studied, multigenerational London family. We report the first whole-exome sequencing (WES) findings from a cohort of 10 unrelated participants, ages 3 to 19 years, with well-characterized CAS.

Stakeholders' opinions on the implementation of pediatric whole exome sequencing: implications for informed consent.

Advances in whole genome and whole exome sequencing (WGS/WES) technologies have led to increased availability in clinical settings. Currently, there are few guidelines relating to the process and content of informed consent for WGS/WES, nor to which results should be returned to families. To address this gap, we conducted focus groups to assess the views of professionals, parents, and adolescents for the future implementation of WES.

Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

Objective: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART.

Design: Observational cohort study of patients initiating ART between January 2000 and December 2005.

Setting: The Antiretroviral Therapy Cohort Collaboration (ART-CC) is a collaboration of 15 HIV cohort studies from Canada, Europe, and the United States.

Alcohol as a primary risk factor in oral squamous carcinoma.

This case-control study investigates the role of alcohol as a primary risk factor in the development of oral cancer. A total of 181 patients diagnosed as having squamous carcinoma of the oral cavity were interviewed, and 497 controls. The relative risk for drinkers adjusted for smoking was 3.