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.

Predicting the Disease Severity of Virus Infection.

The COVID-19 pandemic has resulted in unprecedented burden on global health and economic systems, promoting worldwide efforts to understand, control, and fight the disease. Due to the wide spectrum of clinical severity, effective risk factors, biomarkers, and models for predicting disease severity and mortality in COVID-19 patients are urgently needed to provide guidance for clinical intervention and management. In this chapter, we first describe the infection features of different COVID-19 strains and the potential of clinical features, cytokine storm and biomarkers in predicting the severity of COVID-19 patients. We focus on how scoring systems, mathematical models and artificial intelligence (AI)-based models can promote the classification of COVID-19 severity at the population or individual level. Moreover, the development perspective of biomarkers and models for predicting the severity of COVID-19 is prospected. Therefore, this chapter highlights the clinical significance of biomarkers and models related to COVID-19 severity and provides important clues for improving the outcomes of COVID-19 patients, thereby facilitating timely disease assessment and precision medicine for individual COVID-19 patients.

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/.

Heart Rate Variability Based Prediction of Personalized Drug Therapeutic Response: The Present Status and the Perspectives.

Heart rate variability (HRV) signals are reported to be associated with the personalized drug response in many diseases such as major depressive disorder, epilepsy, chronic pain, hypertension, etc. But the relationships between HRV signals and the personalized drug response in different diseases and patients are complex and remain unclear. With the fast development of modern smart sensor technologies and the popularization of big data paradigm, more and more data on the HRV and drug response will be available, it then provides great opportunities to build models for predicting the association of the HRV with personalized drug response precisely. We here review the present status of the HRV data resources and models for predicting and evaluating of personalized drug responses in different diseases. The future perspectives on the integration of knowledge and personalized data at different levels such as, genomics, physiological signals, etc. for the application of HRV signals to the precision prediction of drug therapy and their response will be provided.

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/.

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.

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.