Harnessing Big Data to Advance Treatment and Understanding of Pulmonary Hypertension

Rhodes, Christopher J.; Sweatt, Andrew J.; Maron, Bradley A.

doi:10.1161/circresaha.121.319969

Cited by 35 publications

(14 citation statements)

References 127 publications

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“…Here, we used network medicine to integrate various big data elements (i.e., metabolic pathways, transcriptomics, and protein-protein interactions) for experimental validation. In doing so, this work achieves a scientific benchmark ( 43 ) in which interconnecting omics optimize the specificity and rigor of outputs ( 44 , 45 ). Since an overarching objective of this study was to ignore a priori assumptions regarding potential links between specific aa and PAH, a strategy such as network medicine that could reduce the initial data set according to functionally relevant pathways was essential.…”

Section: Discussionmentioning

confidence: 99%

Proline and glucose metabolic reprogramming supports vascular endothelial and medial biomass in pulmonary arterial hypertension

Wertheim¹,

Wang²,

Guillermier³

et al. 2023

JCI Insight

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In pulmonary arterial hypertension (PAH), inflammation promotes a fibroproliferative pulmonary vasculopathy. Reductionist studies emphasizing single biochemical reactions suggest a shift toward glycolytic metabolism in PAH; however, key questions remain regarding the metabolic profile of specific cell types within PAH vascular lesions in vivo. We used RNA-seq to profile the transcriptome of pulmonary artery endothelial cells (PAECs) freshly isolated from an inflammatory vascular injury model of PAH ex vivo, and these data were integrated with information from human gene ontology pathways. Network medicine was then used to map all amino acid and glucose pathways to the consolidated human interactome, which includes data on 233,957 physical protein-protein interactions. Glucose and proline pathways were significantly close to the human PAH disease module, suggesting that these pathways are functionally relevant to PAH pathobiology. To test this observation in vivo, we used multi-isotope imaging mass spectrometry (MIMS) to map and quantify utilization of glucose and proline in the PAH pulmonary vasculature at subcellular resolution. Our findings suggest that elevated glucose and proline avidity underlies increased biomass in PAECs and the media of fibrosed PAH pulmonary arterioles. Overall, these data show that anabolic utilization of glucose and proline are fundamental to the vascular pathology of PAH.

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Section: Discussionmentioning

confidence: 99%

Proline and glucose metabolic reprogramming supports vascular endothelial and medial biomass in pulmonary arterial hypertension

Wertheim¹,

Wang²,

Guillermier³

et al. 2023

JCI Insight

Self Cite

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“…Despite the promises of ML, more work is required to validate performance characteristics, expand generalizability, and improve the transparency of ML algorithms. 164 NLP is a collection of automated methods that can be used to extract unstructured data (e.g., clinical notes, imaging reports) and translate them into structured data elements, substantially reducing the time required for manual expert review. NLP is particularly relevant for RWD sources, as more than 80% of EHR data are unstructured.…”

Section: Methods To Improve Rwd Analysis For Ph Populationsmentioning

confidence: 99%

Real‐world evidence to advance knowledge in pulmonary hypertension: Status, challenges, and opportunities. A consensus statement from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative's Real‐world Evidence Working Group

Morland,

Gerges,

Elwing

et al. 2023

Pulm. circ.

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This manuscript on real‐world evidence (RWE) in pulmonary hypertension (PH) incorporates the broad experience of members of the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative Real‐World Evidence Working Group. We aim to strengthen the research community's understanding of RWE in PH to facilitate clinical research advances and ultimately improve patient care. Herein, we review real‐world data (RWD) sources, discuss challenges and opportunities when using RWD sources to study PH populations, and identify resources needed to support the generation of meaningful RWE for the global PH community.

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“…With the wider availability of multiomics platforms as we described in the last section, reconciling information across these omics and other biological data sets has emerged as a contemporary goal defining the field of big data and cardiovascular medicine. 53 The importance of pursuing analyses that facilitate convergence of orthogonal data sets is rooted in several observations. For example, the precision of any individual omics data output hinges, in part, on the methods and analytical tools used to interpret the results.…”

Section: Network Medicine-based Integration Of Multiomics Datamentioning

confidence: 99%

Multiomics Network Medicine Approaches to Precision Medicine and Therapeutics in Cardiovascular Diseases

Wang

Maron

Loscalzo

2023

ATVB

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Cardiovascular diseases (CVD) are the leading cause of death worldwide and display complex phenotypic heterogeneity caused by many convergent processes, including interactions between genetic variation and environmental factors. Despite the identification of a large number of associated genes and genetic loci, the precise mechanisms by which these genes systematically influence the phenotypic heterogeneity of CVD are not well understood. In addition to DNA sequence, understanding the molecular mechanisms of CVD requires data from other omics levels, including the epigenome, the transcriptome, the proteome, as well as the metabolome. Recent advances in multiomics technologies have opened new precision medicine opportunities beyond genomics that can guide precise diagnosis and personalized treatment. At the same time, network medicine has emerged as an interdisciplinary field that integrates systems biology and network science to focus on the interactions among biological components in health and disease, providing an unbiased framework through which to integrate systematically these multiomics data. In this review, we briefly present such multiomics technologies, including bulk omics and single-cell omics technologies, and discuss how they can contribute to precision medicine. We then highlight network medicine-based integration of multiomics data for precision medicine and therapeutics in CVD. We also include a discussion of current challenges, potential limitations, and future directions in the study of CVD using multiomics network medicine approaches.

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Harnessing Big Data to Advance Treatment and Understanding of Pulmonary Hypertension

Cited by 35 publications

References 127 publications

Proline and glucose metabolic reprogramming supports vascular endothelial and medial biomass in pulmonary arterial hypertension

Proline and glucose metabolic reprogramming supports vascular endothelial and medial biomass in pulmonary arterial hypertension

Real‐world evidence to advance knowledge in pulmonary hypertension: Status, challenges, and opportunities. A consensus statement from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative's Real‐world Evidence Working Group

Multiomics Network Medicine Approaches to Precision Medicine and Therapeutics in Cardiovascular Diseases

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