Defining genetic diversity of rhesus macaque Fcγ receptors with long-read RNA sequencing.

Fcγ receptors (FcγRs) are membrane-bound glycoproteins that bind to the fragment crystallizable (Fc) constant regions of IgG antibodies. Interactions between IgG immune complexes and FcγRs can initiate signal transduction that mediates important components of the immune response including activation of immune cells for clearance of opsonized pathogens or infected host cells. In humans, many studies have identified associations between FcγR gene polymorphisms and risk of infection, or progression of disease, suggesting a gene-level impact on FcγR-dependent immune responses.

Multivariate analysis of FcR-mediated NK cell functions identifies unique clustering among humans and rhesus macaques.

Rhesus macaques (RMs) are a common pre-clinical model used to test HIV vaccine efficacy and passive immunization strategies. Yet, it remains unclear to what extent the Fc-Fc receptor (FcR) interactions impacting antiviral activities of antibodies in RMs recapitulate those in humans. Here, we evaluated the FcR-related functionality of natural killer cells (NKs) from peripheral blood of uninfected humans and RMs to identify intra- and inter-species variation.

Functional Homology for Antibody-Dependent Phagocytosis Across Humans and Rhesus Macaques.

Analyses of human clinical HIV-1 vaccine trials and preclinical vaccine studies performed in rhesus macaque (RM) models have identified associations between non-neutralizing Fc Receptor (FcR)-dependent antibody effector functions and reduced risk of infection. Specifically, antibody-dependent phagocytosis (ADP) has emerged as a common correlate of reduced infection risk in multiple RM studies and the human HVTN505 trial. This recurrent finding suggests that antibody responses with the capability to mediate ADP are most likely a desirable component of vaccine responses aimed at protecting against HIV-1 acquisition.

A novel nonsense mutation in TNNT2 in a Chinese pedigree with hypertrophic cardiomyopathy: A case report.

Rationale: Hypertrophic cardiomyopathy (HCM) is an inherited myocardial disease and a common cause of sudden cardiac death, heart failure, atrial fibrillation and stroke. In families affected by HCM, genotyping is useful for identifying susceptible relatives. In the present study, we investigated the disease-causing mutations in a three-generation Chinese family with HCM using whole exome sequencing (WES).

Variant Interpretation for Cancer (VIC): a computational tool for assessing clinical impacts of somatic variants.

Background: Clinical laboratories implement a variety of measures to classify somatic sequence variants and identify clinically significant variants to facilitate the implementation of precision medicine. To standardize the interpretation process, the Association for Molecular Pathology (AMP), American Society of Clinical Oncology (ASCO), and College of American Pathologists (CAP) published guidelines for the interpretation and reporting of sequence variants in cancer in 2017. These guidelines classify somatic variants using a four-tiered system with ten criteria.

Tumoral expression of drug and xenobiotic metabolizing enzymes in breast cancer patients of different ethnicities with implications to personalized medicine.

Drug and xenobiotic metabolizing enzymes (DXME) play important roles in drug responses and carcinogenesis. Recent studies have found that expression of DXME in cancer cells significantly affects drug clearance and the onset of drug resistance. In this study we compared the expression of DXME in breast tumor tissue samples from patients representing three ethnic groups: Caucasian Americans (CA), African Americans (AA), and Asian Americans (AS).

Big Data Analytics for Genomic Medicine.

Genomic medicine attempts to build individualized strategies for diagnostic or therapeutic decision-making by utilizing patients' genomic information. Big Data analytics uncovers hidden patterns, unknown correlations, and other insights through examining large-scale various data sets. While integration and manipulation of diverse genomic data and comprehensive electronic health records (EHRs) on a Big Data infrastructure exhibit challenges, they also provide a feasible opportunity to develop an efficient and effective approach to identify clinically actionable genetic variants for individualized diagnosis and therapy.

Integrative Comparison of mRNA Expression Patterns in Breast Cancers from Caucasian and Asian Americans with Implications for Precision Medicine.

Asian Americans (AS) have significantly lower incidence and mortality rates of breast cancer than Caucasian Americans (CA). Although this racial disparity has been documented, the underlying pathogenetic factors explaining it are obscure. We addressed this issue by an integrative genomics approach to compare mRNA expression between AS and CA cases of breast cancer.

The Decay of Disease Association with Declining Linkage Disequilibrium: A Fine Mapping Theorem.

Several important and fundamental aspects of disease genetics models have yet to be described. One such property is the relationship of disease association statistics at a marker site closely linked to a disease causing site. A complete description of this two-locus system is of particular importance to experimental efforts to fine map association signals for complex diseases.

Pathogenic Mutations in Cancer-Predisposing Genes: A Survey of 300 Patients with Whole-Genome Sequencing and Lifetime Electronic Health Records.

Background: It is unclear whether and how whole-genome sequencing (WGS) data can be used to implement genomic medicine. Our objective is to retrospectively evaluate whether WGS can facilitate improving prevention and care for patients with susceptibility to cancer syndromes.

Methods And Findings: We analyzed genetic mutations in 60 autosomal dominant cancer-predisposition genes in 300 deceased patients with WGS data and nearly complete long-term (over 30 years) medical records.

SparkText: Biomedical Text Mining on Big Data Framework.

Background: Many new biomedical research articles are published every day, accumulating rich information, such as genetic variants, genes, diseases, and treatments. Rapid yet accurate text mining on large-scale scientific literature can discover novel knowledge to better understand human diseases and to improve the quality of disease diagnosis, prevention, and treatment.

Results: In this study, we designed and developed an efficient text mining framework called SparkText on a Big Data infrastructure, which is composed of Apache Spark data streaming and machine learning methods, combined with a Cassandra NoSQL database.

Performing Concomitant Tricuspid Valve Repair at the Time of Mitral Valve Operations Is Not Associated With Increased Operative Mortality.

Background: The performance of concomitant tricuspid valve repair (TVr) at the time of mitral valve repair or replacement (MVRR) has previously been associated with elevated short-term risk. Outcomes were assessed at incremental grades of tricuspid regurgitation (TR) to quantify the contemporary risk of concomitant TVr.

Methods: Between July 2011 and June 2014, 88,473 patients undergoing MVRR were examined using The Society of Thoracic Surgeons database.

3DSEM++: Adaptive and intelligent 3D SEM surface reconstruction.

Structural analysis of microscopic objects is a longstanding topic in several scientific disciplines, such as biological, mechanical, and materials sciences. The scanning electron microscope (SEM), as a promising imaging equipment has been around for decades to determine the surface properties (e.g.

Challenges of Identifying Clinically Actionable Genetic Variants for Precision Medicine.

Advances in genomic medicine have the potential to change the way we treat human disease, but translating these advances into reality for improving healthcare outcomes depends essentially on our ability to discover disease- and/or drug-associated clinically actionable genetic mutations. Integration and manipulation of diverse genomic data and comprehensive electronic health records (EHRs) on a big data infrastructure can provide an efficient and effective way to identify clinically actionable genetic variants for personalized treatments and reduce healthcare costs. We review bioinformatics processing of next-generation sequencing (NGS) data, bioinformatics infrastructures for implementing precision medicine, and bioinformatics approaches for identifying clinically actionable genetic variants using high-throughput NGS data and EHRs.

Association of Arrhythmia-Related Genetic Variants With Phenotypes Documented in Electronic Medical Records.

Importance: Large-scale DNA sequencing identifies incidental rare variants in established Mendelian disease genes, but the frequency of related clinical phenotypes in unselected patient populations is not well established. Phenotype data from electronic medical records (EMRs) may provide a resource to assess the clinical relevance of rare variants.

Objective: To determine the clinical phenotypes from EMRs for individuals with variants designated as pathogenic by expert review in arrhythmia susceptibility genes.

Evaluation of The Society of Thoracic Surgeons Online Risk Calculator for Assessment of Risk in Patients Presenting for Aortic Valve Replacement After Prior Coronary Artery Bypass Graft: An Analysis Using the STS Adult Cardiac Surgery Database.

Background: Accurate risk assessment in patients presenting for aortic valve replacement (AVR) after prior coronary artery bypass grafting (CABG) is essential for appropriate selection of surgical versus percutaneous therapy.

Methods: We included 6,534 patients in The Society for Thoracic Surgeons (STS) Adult Cardiac Surgery Database (October 2009 through December 2013) who underwent elective, isolated reoperative AVR for aortic stenosis after prior CABG. Case-specific PROM was calculated and observed-to-expected ratios were inspected across the spectrum of risk.

Prevalence estimation for monogenic autosomal recessive diseases using population-based genetic data.

Genetic methods can complement epidemiological surveys and clinical registries in determining prevalence of monogenic autosomal recessive diseases. Several large population-based genetic databases, such as the NHLBI GO Exome Sequencing Project, are now publically available. By assuming Hardy-Weinberg equilibrium, the frequency of individuals homozygous in the general population for a particular pathogenic allele can be directly calculated from a sample of chromosomes where some harbor the pathogenic allele.

Epidemiology and outcomes after in-hospital cardiac arrest after pediatric cardiac surgery.

Background: Multicenter data regarding cardiac arrest in children undergoing heart operations are limited. We describe epidemiology and outcomes associated with postoperative cardiac arrest in a large multiinstitutional cohort.

Methods: Patients younger than 18 years in the Society of Thoracic Surgeons Congenital Heart Surgery Database (2007 through 2012) were included.

The expanding role of mitral valve repair in triple valve operations: contemporary North American outcomes in 8,021 patients.

Background: Although the operative risk of multivalve operations has historically been high, current outcomes are poorly understood. We sought to evaluate factors influencing contemporary results of triple-valve operations using The Society of Thoracic Surgeons Adult Cardiac Surgery Database.

Methods: Among patients undergoing combined mitral, aortic, and tricuspid valve (triple- valve) operations between 1993 and 2011, aortic valve repair patients were excluded and those having aortic valve replacement were analyzed according to whether they underwent repair vs replacement of the mitral valve (MV) and tricuspid valve (TV).

LncRNA profile study reveals a three-lncRNA signature associated with the survival of patients with oesophageal squamous cell carcinoma.

Background: Oesophageal cancer is one of the most deadly forms of cancer worldwide. Long non-coding RNAs (lncRNAs) are often found to have important regulatory roles.

Objective: To assess the lncRNA expression profile of oesophageal squamous cell carcinoma (OSCC) and identify prognosis-related lncRNAs.

Incidence and survival of hospitalized acute decompensated heart failure in four US communities (from the Atherosclerosis Risk in Communities Study).

Most population-based estimates of incident hospitalized heart failure (HF) have not differentiated acute decompensated heart failure (ADHF) from chronic stable HF nor included racially diverse populations. The Atherosclerosis Risk in Communities Study conducted surveillance of hospitalized HF events (age ≥55 years) in 4 US communities. We estimated hospitalized ADHF incidence and survival by race and gender.

Isocitrate dehydrogenase 1 is a novel plasma biomarker for the diagnosis of non-small cell lung cancer.

Purpose: Effective biomarkers for the diagnosis of non-small cell lung cancer (NSCLC) are needed. We previously showed that isocitrate dehydrogenase 1 (IDH1) is significantly increased in NSCLC tumors. This study aimed to examine the plasma levels of IDH1 in a large patient population to evaluate its effectiveness in NSCLC diagnosis.

Prediction of incident heart failure in general practice: the Atherosclerosis Risk in Communities (ARIC) Study.

Background: A simple and effective heart failure (HF) risk score would facilitate the primary prevention and early diagnosis of HF in general practice. We examined the external validity of existing HF risk scores, optimized a 10-year HF risk function, and examined the incremental value of several biomarkers, including N-terminal pro-brain natriuretic peptide.

Methods And Results: During 15.

Common carotid artery intima-media thickness is as good as carotid intima-media thickness of all carotid artery segments in improving prediction of coronary heart disease risk in the Atherosclerosis Risk in Communities (ARIC) study.

Aims: Carotid intima-media thickness (CIMT) and plaque information can improve coronary heart disease (CHD) risk prediction when added to traditional risk factors (TRF). However, obtaining adequate images of all carotid artery segments (A-CIMT) may be difficult. Of A-CIMT, the common carotid artery intima-media thickness (CCA-IMT) is relatively more reliable and easier to measure.

Genetic variants in TLR2 and TLR4 are associated with markers of monocyte activation: the Atherosclerosis Risk in Communities MRI Study.

Markers of monocyte activation play a critical role in atherosclerosis, but little is known about the genetic influences on cellular levels. Therefore, we investigated the influence of genetic variants in monocyte differentiation antigen (CD14), toll-like receptor-4 (TLR4), toll-like receptor-2 (TLR2), and myeloperoxidase (MPO) on monocyte surface receptor levels. The study sample consisted of 1,817 members of a biracial cohort of adults from the Atherosclerosis Risk in Communities Carotid MRI Study.