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

MOTIVATION: Heart failure (HF) is a cardiovascular disease with a high incidence around the world. Accumulating studies have focused on the identification of biomarkers for HF precision medicine. To understand the HF heterogeneity and provide biomarker information for the personalized diagnosis and treatment of HF, a knowledge database collecting the distributed and multiple-level biomarker information is necessary. RESULTS: In this study, the HF biomarker knowledge database (HFBD) was established by manually collecting the data and knowledge from literature in PubMed. HFBD contains 2618 records and 868 HF biomarkers (731 single and 137 combined) extracted from 1237 original articles. The biomarkers were classified into proteins, RNAs, DNAs and the others at molecular, image, cellular and physiological levels. The biomarkers were annotated with biological, clinical and article information as well as the experimental methods used for the biomarker discovery. With its user-friendly interface, this knowledge database provides a unique resource for the systematic understanding of HF heterogeneity and personalized diagnosis and treatment of HF in the era of precision medicine. AVAILABILITY AND IMPLEMENTATION: The platform is openly available at http://sysbio.org.cn/HFBD/.

RARPKB: a knowledge-guide decision support platform for personalized robot-assisted surgery in prostate cancer.

BACKGROUND: Robot-assisted radical prostatectomy (RARP) has emerged as a pivotal surgical intervention for the treatment of prostate cancer (PCa). However, the complexity of clinical cases, heterogeneity of PCa, and limitations in physician expertise pose challenges to rational decision-making in RARP. To address these challenges, the authors aimed to organize the knowledge of previously complex cohorts and establish an online platform named the RARP knowledge base (RARPKB) to provide reference evidence for personalized treatment plans. MATERIALS AND METHODS: PubMed searches over the past two decades were conducted to identify publications describing RARP. The authors collected, classified, and structured surgical details, patient information, surgical data, and various statistical results from the literature. A knowledge-guided decision-support tool was established using MySQL, DataTable, ECharts, and JavaScript. ChatGPT-4 and two assessment scales were used to validate and compare the platform. RESULTS: The platform comprised 583 studies, 1589 cohorts, 1 911 968 patients, and 11 986 records, resulting in 54 834 data entries. The knowledge-guided decision support tool provide personalized surgical plan recommendations and potential complications on the basis of patients' baseline and surgical information. Compared with ChatGPT-4, RARPKB outperformed in authenticity (100% vs. 73%), matching (100% vs. 53%), personalized recommendations (100% vs. 20%), matching of patients (100% vs. 0%), and personalized recommendations for complications (100% vs. 20%). Postuse, the average System Usability Scale score was 88.88±15.03, and the Net Promoter Score of RARPKB was 85. The knowledge base is available at: http://rarpkb.bioinf.org.cn . CONCLUSIONS: The authors introduced the pioneering RARPKB, the first knowledge base for robot-assisted surgery, with an emphasis on PCa. RARPKB can assist in personalized and complex surgical planning for PCa to improve its efficacy. RARPKB provides a reference for the future applications of artificial intelligence in clinical practice.

Myocardial infarction unveiled: Key miRNA players screened by a novel lncRNA-miRNA-mRNA network model.

BACKGROUND: Myocardial infarction (MI) is a major contributor to global mortality, and microRNAs (miRNAs) are important in its pathogenesis. Identifying blood miRNAs with clinical application potential for the early detection and treatment of MI is crucial. METHODS: We obtained MI-related miRNA and miRNA microarray datasets from MI Knowledge Base (MIKB) and Gene Expression Omnibus (GEO), respectively. A new feature called target regulatory score (TRS) was proposed to characterize the RNA interaction network. MI-related miRNAs were characterized using TRS, transcription factor (TF) gene proportion (TFP), and ageing-related gene (AG) proportion (AGP) via the lncRNA-miRNA-mRNA network. A bioinformatics model was then developed to predict MI-related miRNAs, which were verified by literature and pathway enrichment analysis. RESULTS: The TRS-characterized model outperformed previous methods in identifying MI-related miRNAs. MI-related miRNAs had high TRS, TFP, and AGP values, and combining the three features improved prediction accuracy to 0.743. With this method, 31 candidate MI-related miRNAs were screened from the specific-MI lncRNA-miRNA-mRNA network, associated with key MI pathways like circulatory system processes, inflammatory response, and oxygen level adaptation. Most candidate miRNAs were directly associated with MI according to literature evidence, except hsa-miR-520c-3p and hsa-miR-190b-5p. Furthermore, CAV1, PPARA and VEGFA were identified as MI key genes, and were targeted by most of the candidate miRNAs. CONCLUSIONS: This study proposed a novel bioinformatics model based on multivariate biomolecular network analysis to identify putative key miRNAs of MI, which deserve further experimental and clinical validation for translational applications.

From multi-omics approaches to personalized medicine in myocardial infarction.

Myocardial infarction (MI) is a prevalent cardiovascular disease characterized by myocardial necrosis resulting from coronary artery ischemia and hypoxia, which can lead to severe complications such as arrhythmia, cardiac rupture, heart failure, and sudden death. Despite being a research hotspot, the etiological mechanism of MI remains unclear. The emergence and widespread use of omics technologies, including genomics, transcriptomics, proteomics, metabolomics, and other omics, have provided new opportunities for exploring the molecular mechanism of MI and identifying a large number of disease biomarkers. However, a single-omics approach has limitations in understanding the complex biological pathways of diseases. The multi-omics approach can reveal the interaction network among molecules at various levels and overcome the limitations of the single-omics approaches. This review focuses on the omics studies of MI, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, and other omics. The exploration extended into the domain of multi-omics integrative analysis, accompanied by a compilation of diverse online resources, databases, and tools conducive to these investigations. Additionally, we discussed the role and prospects of multi-omics approaches in personalized medicine, highlighting the potential for improving diagnosis, treatment, and prognosis of MI.

NDDRF: A risk factor knowledgebase for personalized prevention of neurodegenerative diseases.

INTRODUCTION: Neurodegenerative diseases (NDDs) are a series of chronic diseases, which are associated with progressive loss of neuronal structure or function. The complex etiologies of the NDDs remain unclear, thus the prevention and early diagnosis of NDDs are critical to reducing the mortality and morbidity of these diseases. OBJECTIVES: To provide a systematic understanding of the heterogeneity of the risk factors associated with different NDDs (pan-neurodegenerative diseases or pan-NDDs), the knowledgebase is established to facilitate the personalized and knowledge-guided diagnosis, prevention and prediction of NDDs. METHODS: Before data collection, the medical, lifescienceand informatics experts as well as the potential users of the database were consulted and discussed for the scope of data and the classification of risk factors. The PubMed database was used as the resource of the data and knowledge extraction. Risk factors of NDDs were manually collected from literature published between 1975 and 2020. RESULTS: The comprehensive risk factors database for NDDs (NDDRF) was established including 998 single or combined risk factors, 2293 records and 1071 articles relevant to the 14 most common NDDs. The single risk factors are classified into 3 categories, i.e. epidemiological factors (469), genetic factors (324) and biochemical factors (153). Among all the factors, 179 factors are positive and protective, while 880 factors have negative influence for NDDs. The knowledgebase is available at http://sysbio.org.cn/NDDRF/. CONCLUSION: NDDRF provides the structured information and knowledge resource on risk factors of NDDs. It could benefit the future systematic and personalized investigation of pan-NDDs genesis and progression. Meanwhile it may be used for the future explainable artificial intelligence modeling for smart diagnosis and prevention of NDDs.

MIKB: A manually curated and comprehensive knowledge base for myocardial infarction.

Myocardial infarction knowledge base (MIKB; http://www.sysbio.org.cn/mikb/; latest update: December 31, 2020) is an open-access and manually curated database dedicated to integrating knowledge about MI to improve the efficiency of translational MI research. MIKB is an updated and expanded version of our previous MI Risk Knowledge Base (MIRKB), which integrated MI-related risk factors and risk models for providing help in risk assessment or diagnostic prediction of MI. The updated MIRKB includes 9701 records with 2054 single factors, 209 combined factors, 243 risk models, 37 MI subtypes and 3406 interactions between single factors and MIs collected from 4817 research articles. The expanded functional module, i.e. MIGD, is a database including not only MI associated genetic variants, but also the other multi-omics factors and the annotations for their functional alterations. The goal of MIGD is to provide a multi-omics level understanding of the molecular pathogenesis of MI. MIGD includes 1782 omics factors, 28 MI subtypes and 2347 omics factor-MI interactions as well as 1253 genes and 6 chromosomal alterations collected from 2647 research articles. The functions of MI associated genes and their interaction with drugs were analyzed. MIKB will be continuously updated and optimized to provide precision and comprehensive knowledge for the study of heterogeneous and personalized MI.

Early Detection of Sudden Cardiac Death by Using Ensemble Empirical Mode Decomposition-Based Entropy and Classical Linear Features From Heart Rate Variability Signals.

Sudden cardiac death (SCD), which can deprive a person of life within minutes, is a destructive heart abnormality. Thus, providing early warning information for patients at risk of SCD, especially those outside hospitals, is essential. In this study, we investigated the performances of ensemble empirical mode decomposition (EEMD)-based entropy features on SCD identification. EEMD-based entropy features were obtained by using the following technology: (1) EEMD was performed on HRV beats to decompose them into intrinsic mode functions (IMFs), (2) five entropy parameters, namely Rényi entropy (RenEn), fuzzy entropy (FuEn), dispersion Entropy (DisEn), improved multiscale permutation entropy (IMPE), and Renyi distribution entropy(RdisEn), were computed from the first four IMFs obtained, which were named EEMD-based entropy features. Additionally, an automated scheme combining EEMD-based entropy and classical linear (time and frequency domains) features was proposed with the intention of detecting SCD early by analyzing 14 min (at seven successive intervals of 2 min) heart rate variability (HRV) in signals from a normal population and subjects at risk of SCD. Firstly, EEMD-based entropy and classical linear measurements were extracted from HRV beats, and then the integrated measurements were ranked by various methodologies, i.e., t-test, entropy, receiver-operating characteristics (ROC), Wilcoxon, and Bhattacharyya. Finally, these ranked features were fed into a k-Nearest Neighbor algorithm for classification. Compared with several state-of-the-art methods, the proposed scheme firstly predicted subjects at risk of SCD up to 14 min earlier with an accuracy of 96.1%, a sensitivity of 97.5%, and a specificity of 94.4% 14 min before SCD onset. The simulation results exhibited that EEMD-based entropy estimators showed significant difference between SCD patients and normal individuals and outperformed the classical linear estimators in SCD detection, the EEMD-based FuEn and IMPE indexes were particularly useful assessments for identification of patients at risk of SCD and can be used as novel indices to reveal the disorders of rhythm variations of the autonomic nervous system when affected by SCD.

Phenotype-genotype network construction and characterization: a case study of cardiovascular diseases and associated non-coding RNAs.

The phenotype-genotype relationship is a key for personalized and precision medicine for complex diseases. To unravel the complexity of the clinical phenotype-genotype network, we used cardiovascular diseases (CVDs) and associated non-coding RNAs (ncRNAs) (i.e. miRNAs, long ncRNAs, etc.) as the case for the study of CVDs at a systems or network level. We first integrated a database of CVDs and ncRNAs (CVDncR, http://sysbio.org.cn/cvdncr/) to construct CVD-ncRNA networks and annotate their clinical associations. To characterize the networks, we then separated the miRNAs into two groups, i.e. universal miRNAs associated with at least two types of CVDs and specific miRNAs related only to one type of CVD. Our analyses indicated two interesting patterns in these CVD-ncRNA networks. First, scale-free features were present within both CVD-miRNA and CVD-lncRNA networks; second, universal miRNAs were more likely to be CVDs biomarkers. These results were confirmed by computational functional analyses. The findings offer theoretical guidance for decoding CVD-ncRNA associations and will facilitate the screening of CVD ncRNA biomarkers. Database URL: http://sysbio.org.cn/cvdncr/.

Renyi Distribution Entropy Analysis of Short-Term Heart Rate Variability Signals and Its Application in Coronary Artery Disease Detection.

Coronary artery disease (CAD) is a life-threatening condition that, unless treated at an early stage, can lead to congestive heart failure, ischemic heart disease, and myocardial infarction. Early detection of diagnostic features underlying electrocardiography signals is crucial for the identification and treatment of CAD. In the present work, we proposed novel entropy called Renyi Distribution Entropy (RdisEn) for the analysis of short-term heart rate variability (HRV) signals and the detection of CAD. Our simulation experiment with synthetic, physiological, and pathological signals demonstrated that RdisEn could distinguish effectively among different subject groups. Compared to the values of sample entropy or approximation entropy, the RdisEn value was less affected by the parameter choice, and it remained stable even in short-term HRV. We have developed a combined CAD detection scheme with RdisEn and wavelet packet decomposition (WPD): (1) Normal and CAD HRV beats obtained were divided into two equal parts. (2) Feature acquisition: RdisEn and WPD-based statistical features were calculated from one part of HRV beats, and student's t-test was performed to select clinically significant features. (3) Classification: selected features were computed from the remaining part of HRV beats and fed into K-nearest neighbor and support vector machine, to separate CAD from normal subjects. The proposed scheme automatically detected CAD with 97.5% accuracy, 100% sensitivity and 95% specificity and performed better than most of the existing schemes.

MIRKB: a myocardial infarction risk knowledge base.

Myocardial infarction (MI) is a common cardiovascular disease and a leading cause of death worldwide. The etiology of MI is complicated and not completely understood. Many risk factors are reported important for the development of MI, including lifestyle factors, environmental factors, psychosocial factors, genetic factors, etc. Identifying individuals with an increased risk of MI is urgent and a major challenge for improving prevention. The MI risk knowledge base (MIRKB) is developed for facilitating MI research and prevention. The goal of MIRKB is to collect risk factors and models related to MI to increase the efficiency of systems biological level understanding of the disease. MIRKB contains 8436 entries collected from 4366 articles in PubMed before 5 July 2019 with 7902 entries for 1847 single factors, 195 entries for 157 combined factors and 339 entries for 174 risk models. The single factors are classified into the following five categories based on their characteristics: molecular factor (2356 entries, 649 factors), imaging (821 entries, 252 factors), physiological factor (1566 entries, 219 factors), clinical factor (2523 entries, 561 factors), environmental factor (46 entries, 26 factors), lifestyle factor (306 entries, 65 factors) and psychosocial factor (284 entries, 75 factors). MIRKB will be helpful to the future systems level unraveling of the complex mechanism of MI genesis and progression.