HFBD: a biomarker knowledge database for heart failure heterogeneity and personalized applications

He, Hongxin; Shi, Manhong; Lin, Yuxin; Zhan, Chaoying; Bi, Cheng; Liu, Xingyun; Ren, Shumin; Shen, Bairong

doi:10.1093/bioinformatics/btab470

Cited by 11 publications

(5 citation statements)

References 33 publications

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“…We surveyed the literature and existing databases that list known RNA biomarkers to identify additional evidence for genes that we found in our analyses (Additional file 3 : Table S2). For example, we checked the Heart Failure database for known RNA biomarkers (HFBD) [ 43 ], but none of the 49 ncRNAs listed there overlapped ours.…”

Section: Resultsmentioning

confidence: 99%

CVD-associated SNPs with regulatory potential reveal novel non-coding disease genes

Zhu¹,

Baumgarten²,

Wu³

et al. 2023

Hum Genomics

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Background Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Genome-wide association studies (GWAS) have identified many single nucleotide polymorphisms (SNPs) appearing in non-coding genomic regions in CVDs. The SNPs may alter gene expression by modifying transcription factor (TF) binding sites and lead to functional consequences in cardiovascular traits or diseases. To understand the underlying molecular mechanisms, it is crucial to identify which variations are involved and how they affect TF binding. Methods The SNEEP (SNP exploration and analysis using epigenomics data) pipeline was used to identify regulatory SNPs, which alter the binding behavior of TFs and link GWAS SNPs to their potential target genes for six CVDs. The human-induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs), monoculture cardiac organoids (MCOs) and self-organized cardiac organoids (SCOs) were used in the study. Gene expression, cardiomyocyte size and cardiac contractility were assessed. Results By using our integrative computational pipeline, we identified 1905 regulatory SNPs in CVD GWAS data. These were associated with hundreds of genes, half of them non-coding RNAs (ncRNAs), suggesting novel CVD genes. We experimentally tested 40 CVD-associated non-coding RNAs, among them RP11-98F14.11, RPL23AP92, IGBP1P1, and CTD-2383I20.1, which were upregulated in hiPSC-CMs, MCOs and SCOs under hypoxic conditions. Further experiments showed that IGBP1P1 depletion rescued expression of hypertrophic marker genes, reduced hypoxia-induced cardiomyocyte size and improved hypoxia-reduced cardiac contractility in hiPSC-CMs and MCOs. Conclusions IGBP1P1 is a novel ncRNA with key regulatory functions in modulating cardiomyocyte size and cardiac function in our disease models. Our data suggest ncRNA IGBP1P1 as a potential therapeutic target to improve cardiac function in CVDs.

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Section: Resultsmentioning

confidence: 99%

CVD-associated SNPs with regulatory potential reveal novel non-coding disease genes

Zhu¹,

Baumgarten²,

Wu³

et al. 2023

Hum Genomics

View full text Add to dashboard Cite

show abstract

“…We surveyed the literature and existing databases that list known RNA biomarkers to identify additional evidence for genes that we found in our analyses (Table S2). For example, we checked the Heart Failure database for known RNA biomarkers (HFBD), 39 but none of the 49 ncRNAs listed there overlapped ours.…”

Section: Resultsmentioning

confidence: 99%

CVD-associated SNPs with regulatory potential drive pathologic non-coding RNA expression

Zhu

Baumgarten

et al. 2023

Preprint

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Background: Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Genome-wide association studies (GWAS) have identified many single nucleotide polymorphisms (SNPs) appearing in non-coding genomic regions in CVDs. The SNPs may alter gene expression by modifying transcription factor (TF) binding sites and lead to functional consequences in cardiovascular traits or diseases. To understand the underlying molecular mechanisms, it is crucial to identify which variations are involved and how they affect TF binding. Methods: The SNEEP (SNP exploration and analysis using epigenomics data) pipeline was used to identify regulatory SNPs, which alter the binding behavior of TFs and link GWAS SNPs to their potential target genes for six CVDs. The human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs), monoculture cardiac organoids (MCOs) and self-organized cardiac organoids (SCOs) were used in the study. Gene expression, cardiomyocyte size and cardiac contractility were assessed. Results: By using our integrative computational pipeline, we identified 1905 regulatory SNPs in CVD GWAS data. These were associated with hundreds of genes, half of them non-coding RNAs (ncRNAs), suggesting novel CVD genes. We experimentally tested 40 CVD-associated non-coding RNAs, among them RP11-98F14.11, RPL23AP92, IGBP1P1, and CTD-2383I20.1, which were upregulated in hiPSC-CMs, MCOs and SCOs under hypoxic conditions. Further experiments showed that IGBP1P1 depletion rescued expression of hypertrophic marker genes, reduced hypoxia-induced cardiomyocyte size and improved hypoxia-reduced cardiac contractility in hiPSC-CMs and MCOs. Conclusions: IGBP1P1 is a novel ncRNA with key regulatory functions in modulating cardiomyocyte size and cardiac function in our disease models. Our data suggest ncRNA IGBP1P1 as a potential therapeutic target to improve cardiac function in CVDs.

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“…There are several biomarker databases for human complex diseases: CBD for colorectal cancers ( Zhang et al 2018 ), HFBD for Heart failure ( He et al 2021 ), and IDBD for infectious diseases ( Yang et al 2008 ). Our study fills the gap of a missing biomarker database for ophthalmology.…”

Section: Discussionmentioning

confidence: 99%

EBD: an eye biomarker database

et al. 2023

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Motivation Many ophthalmic disease biomarkers have been identified through comprehensive multi-omics profiling, and hold significant potential in advancing the diagnosis, prognosis, and management of diseases. Meanwhile, the eye itself serves as a natural biomarker for several systemic diseases including neurological, renal and cardiovascular systems. We aimed to collect and standardize these eye biomarkers information and construct the eye biomarker database (EBD) to provide ophthalmologists with a platform to search, analyse and download these eye biomarker data. Results Data were collected from published papers, and the database was constructed based on the MySQL server. Biological network and functional analysis were conducted to analyse biomarkers in-network and pathway levels. In this study, we present the Eye Biomarker Database (EBD) <http://www.eyeseeworld.com/ebd/index.html>, a world-first online compilation comprising 889 biomarkers for 26 ocular diseases and 939 eye biomarkers for 181 systemic diseases. The EBD also includes the information of 78 “non-biomarkers”—the objects that have been proven cannot be biomarkers. Biological function and network analysis were conducted for these ocular disease biomarkers, and several hub pathways and common network topology characteristics were newly identified, which may promote future ocular disease biomarker discovery and characterizes the landscape of biomarkers for eye diseases at the pathway and network level. The EBD is expected to yield broader utility among developmental biologists and clinical scientists in and outside of the eye field by assisting in the identification of biomarkers linked to eye disorders and related systemic diseases. Availability EBD is available at http://www.eyeseeworld.com/ebd/index.html Supplementary information Supplementary data are available at Bioinformatics online.

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HFBD: a biomarker knowledge database for heart failure heterogeneity and personalized applications

Cited by 11 publications

References 33 publications

CVD-associated SNPs with regulatory potential reveal novel non-coding disease genes

CVD-associated SNPs with regulatory potential reveal novel non-coding disease genes

CVD-associated SNPs with regulatory potential drive pathologic non-coding RNA expression

EBD: an eye biomarker database

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