Proteomics of left ventricular structure in the Multi-Ethnic Study of Atherosclerosis.

Aims: Proteomic profiling offers an expansive approach to biomarker discovery and mechanistic hypothesis generation for LV remodelling, a critical component of heart failure (HF). We sought to identify plasma proteins cross-sectionally associated with left ventricular (LV) size and geometry in a diverse population-based cohort without known cardiovascular disease (CVD).

Methods And Results: Among participants of the Multi-Ethnic Study of Atherosclerosis (MESA), we quantified plasma abundances of 1305 proteins using an aptamer-based platform at exam 1 (2000-2002) and exam 5 (2010-2011) and assessed LV structure by cardiac magnetic resonance (CMR) at the same time points.

Dynamic and prognostic proteomic associations with FEV decline in chronic obstructive pulmonary disease.

Rationale: Identification and validation of circulating biomarkers for lung function decline in COPD remains an unmet need.

Objective: Identify prognostic and dynamic plasma protein biomarkers of COPD progression.

Methods: We measured plasma proteins using SomaScan from two COPD-enriched cohorts, the Subpopulations and Intermediate Outcomes Measures in COPD Study (SPIROMICS) and Genetic Epidemiology of COPD (COPDGene), and one population-based cohort, Multi-Ethnic Study of Atherosclerosis (MESA) Lung.

An end is in sight: a perspective on PCR as an endpoint for Chagas disease treatment trials.

Novel therapies for chronic indeterminate Chagas disease (CICD) are needed, but trials are limited by the absence of tests to detect infection and early treatment efficacy. This perspective highlights the shortfalls and strengths of polymerase chain reaction (PCR) as a study endpoint for anti-parasitic drug development. Serologic reversion, the gold standard test of cure, may take decades to occur in adults and therefore is challenging as an endpoint for drug development.

Protein-metabolite association studies identify novel proteomic determinants of metabolite levels in human plasma.

Although many novel gene-metabolite and gene-protein associations have been identified using high-throughput biochemical profiling, systematic studies that leverage human genetics to illuminate causal relationships between circulating proteins and metabolites are lacking. Here, we performed protein-metabolite association studies in 3,626 plasma samples from three human cohorts. We detected 171,800 significant protein-metabolite pairwise correlations between 1,265 proteins and 365 metabolites, including established relationships in metabolic and signaling pathways such as the protein thyroxine-binding globulin and the metabolite thyroxine, as well as thousands of new findings.

Large scale proteomic studies create novel privacy considerations.

Privacy protection is a core principle of genomic but not proteomic research. We identified independent single nucleotide polymorphism (SNP) quantitative trait loci (pQTL) from COPDGene and Jackson Heart Study (JHS), calculated continuous protein level genotype probabilities, and then applied a naïve Bayesian approach to link SomaScan 1.3K proteomes to genomes for 2812 independent subjects from COPDGene, JHS, SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) and Multi-Ethnic Study of Atherosclerosis (MESA).

Protein Markers of Diabetes Discovered in an African American Cohort.

Proteomics has been used to study type 2 diabetes, but the majority of available data are from White participants. Here, we extend prior work by analyzing a large cohort of self-identified African Americans in the Jackson Heart Study (n = 1,313). We found 325 proteins associated with incident diabetes after adjusting for age, sex, and sample batch (false discovery rate q < 0.

Development and validation of a metabolite index for obstructive sleep apnea across race/ethnicities.

Obstructive sleep apnea (OSA) is a common disorder characterized by recurrent episodes of upper airway obstruction during sleep resulting in oxygen desaturation and sleep fragmentation, and associated with increased risk of adverse health outcomes. Metabolites are being increasingly used for biomarker discovery and evaluation of disease processes and progression. Studying metabolomic associations with OSA in a diverse community-based cohort may provide insights into the pathophysiology of OSA.

Differences in Metabolomic Profiles Between Black and White Women and Risk of Coronary Heart Disease: an Observational Study of Women From Four US Cohorts.

Background: Racial differences in metabolomic profiles may reflect underlying differences in social determinants of health by self-reported race and may be related to racial disparities in coronary heart disease (CHD) among women in the United States. However, the magnitude of differences in metabolomic profiles between Black and White women in the United States has not been well-described. It also remains unknown whether such differences are related to differences in CHD risk.

Nontargeted and Targeted Metabolomic Profiling Reveals Novel Metabolite Biomarkers of Incident Diabetes in African Americans.

Nontargeted metabolomics methods have increased potential to identify new disease biomarkers, but assessments of the additive information provided in large human cohorts by these less biased techniques are limited. To diversify our knowledge of diabetes-associated metabolites, we leveraged a method that measures 305 targeted or "known" and 2,342 nontargeted or "unknown" compounds in fasting plasma samples from 2,750 participants (315 incident cases) in the Jackson Heart Study (JHS)-a community cohort of self-identified African Americans-who are underrepresented in omics studies. We found 307 unique compounds (82 known) associated with diabetes after adjusting for age and sex at a false discovery rate of <0.

Proteomics and Population Biology in the Cardiovascular Health Study (CHS): design of a study with mentored access and active data sharing.

Background: In the last decade, genomic studies have identified and replicated thousands of genetic associations with measures of health and disease and contributed to the understanding of the etiology of a variety of health conditions. Proteins are key biomarkers in clinical medicine and often drug-therapy targets. Like genomics, proteomics can advance our understanding of biology.

Influence of Increasing Age and Body Mass Index of Gender in COVID-19 Patients.

The impact of gender on outcomes in patients suffering from coronavirus disease 2019 (COVID-19) is frequently debated. However, the synchronous influence of additional risk factors is seldom mentioned. With increasing emphasis on identifying patients who are at risk of complications from COVID-19, we decided to conduct a retrospective review to assess the influence of age and body mass index (BMI) on gender-based differences in outcomes.

Metabolomic Analysis of Coronary Heart Disease in an African American Cohort From the Jackson Heart Study.

Importance: African American individuals have disproportionate rates of coronary heart disease (CHD) but lower levels of coronary artery calcium (CAC), a marker of subclinical CHD, than non-Hispanic White individuals. African American individuals may have distinct metabolite profiles associated with incident CHD risk compared with non-Hispanic White individuals, and examination of these differences could highlight important processes that differ between them.

Objectives: To identify novel biomarkers of incident CHD and CAC among African American individuals and to replicate incident CHD findings in a multiethnic cohort.

Soluble Urokinase Plasminogen Activator Receptor: Genetic Variation and Cardiovascular Disease Risk in Black Adults.

Background: suPAR (Soluble urokinase plasminogen activator receptor) has emerged as an important biomarker of coagulation, inflammation, and cardiovascular disease (CVD) risk. The contribution of suPAR to CVD risk and its genetic influence in Black populations have not been evaluated.

Methods: We measured suPAR in 3492 Black adults from the prospective, community-based JHS (Jackson Heart Study).

ADAMTSL2 protein and a soluble biomarker signature identify at-risk non-alcoholic steatohepatitis and fibrosis in adults with NAFLD.

Background & Aims: Identifying fibrosis in non-alcoholic fatty liver disease (NAFLD) is essential to predict liver-related outcomes and guide treatment decisions. A protein-based signature of fibrosis could serve as a valuable, non-invasive diagnostic tool. This study sought to identify circulating proteins associated with fibrosis in NAFLD.

Tie2 activation protects against prothrombotic endothelial dysfunction in COVID-19.

Endothelial dysfunction accompanies the microvascular thrombosis commonly observed in severe COVID-19. Constitutively, the endothelial surface is anticoagulant, a property maintained at least in part via signaling through the Tie2 receptor. During inflammation, the Tie2 antagonist angiopoietin-2 (Angpt-2) is released from endothelial cells and inhibits Tie2, promoting a prothrombotic phenotypic shift.

Tie2 activation protects against prothrombotic endothelial dysfunction in COVID-19.

Profound endothelial dysfunction accompanies the microvascular thrombosis commonly observed in severe COVID-19. In the quiescent state, the endothelial surface is anticoagulant, a property maintained at least in part via constitutive signaling through the Tie2 receptor. During inflammation, the Tie2 antagonist angiopoietin-2 (Angpt-2) is released from activated endothelial cells and inhibits Tie2, promoting a prothrombotic phenotypic shift.

Multiomic Profiling in Black and White Populations Reveals Novel Candidate Pathways in Left Ventricular Hypertrophy and Incident Heart Failure Specific to Black Adults.

Background: Increased left ventricular (LV) mass is associated with adverse cardiovascular events including heart failure (HF). Both increased LV mass and HF disproportionately affect Black individuals. To understand the underlying mechanisms, we undertook a proteomic screen in a Black cohort and compared the findings to results from a White cohort.

Longitudinal proteomic analysis of severe COVID-19 reveals survival-associated signatures, tissue-specific cell death, and cell-cell interactions.

Mechanisms underlying severe coronavirus disease 2019 (COVID-19) disease remain poorly understood. We analyze several thousand plasma proteins longitudinally in 306 COVID-19 patients and 78 symptomatic controls, uncovering immune and non-immune proteins linked to COVID-19. Deconvolution of our plasma proteome data using published scRNA-seq datasets reveals contributions from circulating immune and tissue cells.