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JUMPn: A Streamlined Application for Protein Co-Expression Clustering and Network Analysis in Proteomics
Published on: October 19, 2021
Platelet systems biology using integrated genetic and proteomic platforms
1Department of Medicine, Stony Brook University, Stony Brook, NY 11794-8151, USA. wadie.bahou@sbumed.org
Abstract:
Platelets retain megakaryocyte-derived mRNA, an abundant and diverse array of miRNAs, and have evolved unique adaptive signals for maintenance of genetic and protein diversity. Quiescent platelets generally display minimal translational activity, although maximally-activated platelets retain the capacity for protein synthesis. Progressive data using multiple platelet activation models clearly demonstrate that platelet responses to the majority (if not all) agonists are highly variable within the population, demonstrating considerable heritability in siblings, twins, and families with premature coronary artery disease. Research from our laboratory has adapted global profiling strategies to close the knowledge gap currently existing between genetic variability and platelet phenotypic responsiveness. We have applied iterative algorithms for genetic biomarker discovery and class prediction models of platelet phenotypes, with the goal of systematically analyzing integrated mRNA/miRNA/proteomic datasets for identification of regulatory networks that define phenotypic variability in platelet responses. This approach has the potential to define platelet genetic biomarkers predictive of thrombohemorrhagic outcomes in both normal and widely disparate clinical conditions.
Insights
Platelets contain diverse genetic material and show variable responses to stimuli, influenced by heritability. This study identifies genetic biomarkers to predict platelet function and clinical outcomes.
Area of Science:
- * Hematology and Molecular Biology
- * Genomics and Proteomics
- * Cardiovascular Research
Background:
- * Platelets store mRNA and microRNAs (miRNAs) from megakaryocytes, contributing to genetic and protein diversity.
- * Platelet translational activity is minimal in quiescent states but present upon maximal activation.
- * Platelet responses to agonists exhibit significant population variability and heritability, particularly in cardiovascular disease contexts.
Purpose of the Study:
- * To bridge the knowledge gap between genetic variability and platelet functional responsiveness.
- * To identify genetic biomarkers for predicting platelet phenotypes and clinical outcomes.
- * To systematically analyze integrated omics data for regulatory networks governing platelet response variability.
Main Methods:
- * Adaptation of global profiling strategies for comprehensive platelet analysis.
- * Application of iterative algorithms for genetic biomarker discovery.
- * Development of class prediction models for platelet phenotypes.
- * Integrated analysis of mRNA, miRNA, and proteomic datasets.
Main Results:
- * Demonstrated significant heritability in platelet responses across different populations.
- * Identified potential regulatory networks underlying phenotypic variability in platelet function.
- * Established a framework for analyzing integrated omics data in platelets.
Conclusions:
- * Platelet response variability is substantially influenced by genetic factors.
- * Integrated omics analysis can uncover key regulatory networks in platelet function.
- * This approach holds potential for discovering platelet genetic biomarkers predictive of thrombohemorrhagic events.
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