Finding a Needle in a Haystack

Michelhaugh, Sam A.; Januzzi, James L.

doi:10.1016/j.jacbts.2020.07.007

Cited by 22 publications

(7 citation statements)

References 52 publications

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“…Recent HCM and DCM genome-wide association studies (GWAS) of common DNA variants (with individually small effects on disease) have identified overlapping loci for cardiomyopathies. Tadros, Francis, Xu, Vermeer, et al (2021) [155] showed an opposing relationship between HCM-and DCM-associated common DNA variants and left ventricular measures of structure and function through analyses of the common variants [155]. Genetic correlation between the left ventricular measures of structure and function had divergent relationships with HCM and DCM (most strikingly with end-systolic volume [LVESV; DCM+, HCM-], ejection fraction [LVEF; HCM+, DCM-], and measures of strain [HCM+, DCM-]).…”

Section: Overlapping and Opposing Genetic Factors Of Hcm And Dcmmentioning

confidence: 99%

The Genetic Factors Influencing Cardiomyopathies and Heart Failure across the Allele Frequency Spectrum

Mukhopadhyay,

Dixit,

Khanom

et al. 2024

J. of Cardiovasc. Trans. Res.

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Heart failure (HF) remains a major cause of mortality and morbidity worldwide. Understanding the genetic basis of HF allows for the development of disease-modifying therapies, more appropriate risk stratification, and personalised management of patients. The advent of next-generation sequencing has enabled genome-wide association studies; moving beyond rare variants identified in a Mendelian fashion and detecting common DNA variants associated with disease. We summarise the latest GWAS and rare variant data on mixed and refined HF aetiologies, and cardiomyopathies. We describe the recent understanding of the functional impact of titin variants and highlight FHOD3 as a novel cardiomyopathy-associated gene. We describe future directions of research in this field and how genetic data can be leveraged to improve the care of patients with HF. Graphical Abstract

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Section: Overlapping and Opposing Genetic Factors Of Hcm And Dcmmentioning

confidence: 99%

The Genetic Factors Influencing Cardiomyopathies and Heart Failure across the Allele Frequency Spectrum

Mukhopadhyay,

Dixit,

Khanom

et al. 2024

J. of Cardiovasc. Trans. Res.

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“…Global measures of protein abundance and modifications (proteomics) provide a complementary view to that of transcriptomics, with advantages including proximity to cellular function and the utility of proteins as clinical biomarkers. A variety of proteomics technologies have been applied for heart failure proteomics, including mass spectrometry, protein microarray, aptamers and proximity extension arrays, each of which has its advantages (Michelhaugh & Januzzi, 2020). In a wide survey of the field, an American Heart Association consensus statement noted the broad potential of proteomics to establish cause‐and‐effect mechanisms and signalling networks of cardiovascular disease (Lindsey et al., 2015).…”

Section: Technical Innovations To Assess Biological Diversitymentioning

confidence: 99%

Diversity of cells and signals in the cardiovascular system

Grandi

Navedo

Saucerman

et al. 2023

The Journal of Physiology

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support-information-section). Ele Grandi is a Professor in the Department of Pharmacology, the Chair of the Biophysics Graduate Group, and a Chancellor's Fellow at the University of California Davis. Her research utilizes mathematical modelling and simulation as an interpretative and predictive science to investigate the mechanisms of cardiac arrhythmias. Manuel F. Navedo is a Professor in the Department of Pharmacology and the Chair of the Molecular, Cellular and Integrative Physiology Graduate Group at UC Davis. He is an established physiologist and vascular biologist examining mechanisms regulating vascular smooth muscle function in health and disease. Jeffrey J. Saucerman is a Professor of Biomedical Engineering and Cardiovascular Medicine at the University of Virginia. His research develops experimental and computational methods to discover molecular networks that regulate cardiac remodelling.

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“…In the last decade, high-throughput proteomics technologies using affinity reagents have emerged that have the potential to respond to the stated need [ 5 ]. These affinity-based technologies rely on different methods to measure a large number of proteins: one method which currently targets approximately 7000 human proteins uses slow off-rate modified aptamers (SOMAmer) which are modified short, single-stranded oligonucleotides as protein-binding reagents which are quantifiable by nucleic acid microarrays [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Proteomics for heart failure risk stratification: a systematic review

Kuku,

Oyetoro,

Hashemian

et al. 2024

BMC Med

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Background Heart failure (HF) is a complex clinical syndrome with persistently high mortality. High-throughput proteomic technologies offer new opportunities to improve HF risk stratification, but their contribution remains to be clearly defined. We aimed to systematically review prognostic studies using high-throughput proteomics to identify protein signatures associated with HF mortality. Methods We searched four databases and two clinical trial registries for articles published from 2012 to 2023. HF proteomics studies measuring high numbers of proteins using aptamer or antibody-based affinity platforms on human plasma or serum with outcomes of all-cause or cardiovascular death were included. Two reviewers independently screened articles, extracted data, and assessed the risk of bias. A third reviewer resolved conflicts. We assessed the risk of bias using the Risk Of Bias In Non-randomized Studies—of Exposure tool. Results Out of 5131 unique articles identified, nine articles were included in the review. The nine studies were observational; three used the aptamer platform, and six used the antibody platform. We found considerable heterogeneity across studies in measurement panels, HF definitions, ejection fraction categorization, follow-up duration, and outcome definitions, and a lack of risk estimates for most protein associations. Hence, we proceeded with a systematic review rather than a meta-analysis. In two comparable aptamer studies in patients with HF with reduced ejection fraction, 21 proteins were identified in common for the association with all-cause death. Among these, one protein, WAP four-disulfide core domain protein 2 was also reported in an antibody study on HFrEF and for the association with CV death. We proposed standardized reporting criteria to facilitate the interpretation of future studies. Conclusions In this systematic review of nine studies evaluating the association of proteomics with mortality in HF, we identified a limited number of proteins common across several studies. Heterogeneity across studies compromised drawing broad inferences, underscoring the importance of standardized approaches to reporting.

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Finding a Needle in a Haystack

Cited by 22 publications

References 52 publications

The Genetic Factors Influencing Cardiomyopathies and Heart Failure across the Allele Frequency Spectrum

The Genetic Factors Influencing Cardiomyopathies and Heart Failure across the Allele Frequency Spectrum

Diversity of cells and signals in the cardiovascular system

Proteomics for heart failure risk stratification: a systematic review

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