Through the developments of Omics technologies and dissemination of large-scale datasets, such as those from The Cancer Genome Atlas, Alzheimer’s Disease Neuroimaging Initiative, and Genotype-Tissue Expression, it is becoming increasingly possible to study complex biological processes and disease mechanisms more holistically. However, to obtain a comprehensive view of these complex systems, it is crucial to integrate data across various Omics modalities, and also leverage external knowledge available in biological databases. This review aims to provide an overview of multi-Omics data integration methods with different statistical approaches, focusing on unsupervised learning tasks, including disease onset prediction, biomarker discovery, disease subtyping, module discovery, and network/pathway analysis. We also briefly review feature selection methods, multi-Omics data sets, and resources/tools that constitute critical components for carrying out the integration.
Background Cardiovascular diseases (CVDs) are the number one cause of global mortality representing about one third of all deaths across the world. The objective of the present study was to model the global trend in disability-adjusted life years (DALY) and its components due to CVD over the past three decades. We also aimed to evaluate the longitudinal relationship between CVD DALY and Human Development Index (HDI) in this period of time. Methods The age-standardized rates of years lost due to disability (YLD), years of life lost (YLL) and DALY were extracted for cardiovascular diseases from the Global Burden of Disease (GBD) Study 2019 in years 1990 to 2019. Additionally, the United Nations Development Programme (UNDP) database was used to retrieve HDI values for all world countries at the same period time. The trend analysis was performed using the joinpoint regression model. Results The obtained revealed a significant downward trend for DALY and its components with the average annual percent change of − 1.0, − 0.3 and − 1.1 per 100,000 population, respectively for DALY, YLD and YLL. We also found that countries with high/very high levels of HDI have remarkably experienced steeper declining slope of trend than those in lower levels of HDI over the study period. Conclusions Although the observed decreasing trend of CVD burden is a hopeful message for all world countries, the considerable gap in slope of trend between richer and poorer parts of the world is a serious alarm for health policy makers. Regarding this, there is an urgent need to put more efforts on implementing preventive programs, improving the level of patients’ care and providing efficient treatment, especially in regions with lower levels of HDI.
Heart failure with preserved ejection fraction (HFpEF) patients who develop pulmonary hypertension (PH) have an increased risk of death, with combined pre- and post-capillary PH (CpcPH) having the highest risk. However, the mechanism behind PH development in HFpEF is poorly understood. We aimed to identify transcriptomic associations with PH development in HFpEF. Blood was collected from 30 HFpEF patients: 10 without PH, 10 with isolated post-capillary PH, and 10 with CpcPH. Gene expression measurements were completed using transcriptome-wide RNA sequencing. Gene expression differences were compared using a quasi-likelihood method adjusting for age, sex, race, and smoking-status. Biological pathways were compared using global gene expression differences. A replication in 34 additional heart failure patients and a validation in lung tissue from a representative mouse model were completed using quantitative PCR. Six differentially expressed genes were identified when comparing transcriptomics between subjects with CpcPH and those without PH. When tested in additional subjects, only the association with ID2 replicated. Consistent with clinical findings, Id2 expression was also upregulated in mice with HFpEF and PH. Pathway analysis identified proliferative and mitochondrial pathways associated with CpcPH. Thus, these patients may possess systemic pathophysiological differences similar to those observed in pulmonary arterial hypertension patients.
As of November 12, 2020, the mortality to incidence ratio (MIR) of COVID-19 was 5.8% in the US. A longitudinal model-based clustering system on the disease trajectories over time was used to identify “vulnerable” clusters of counties that would benefit from allocating additional resources by federal, state and county policymakers. County-level COVID-19 cases and deaths, together with a set of potential risk factors were collected for 3050 U.S. counties during the 1st wave of COVID-19 (Mar25–Jun3, 2020), followed by similar data for 1344 counties (in the “sunbelt” region of the country) during the 2nd wave (Jun4–Sep2, 2020), and finally for 1055 counties located broadly in the great plains region of the country during the 3rd wave (Sep3–Nov12, 2020). We used growth mixture models to identify clusters of counties exhibiting similar COVID-19 MIR growth trajectories and risk-factors over time. The analysis identifies “more vulnerable” clusters during the 1st, 2nd and 3rd waves of COVID-19. Further, tuberculosis (OR 1.3–2.1–3.2), drug use disorder (OR 1.1), hepatitis (OR 13.1), HIV/AIDS (OR 2.3), cardiomyopathy and myocarditis (OR 1.3), diabetes (OR 1.2), mesothelioma (OR 9.3) were significantly associated with increased odds of being in a more vulnerable cluster. Heart complications and cancer were the main risk factors increasing the COVID-19 MIR (range 0.08–0.52% MIR↑). We identified “more vulnerable” county-clusters exhibiting the highest COVID-19 MIR trajectories, indicating that enhancing the capacity and access to healthcare resources would be key to successfully manage COVID-19 in these clusters. These findings provide insights for public health policymakers on the groups of people and locations they need to pay particular attention while managing the COVID-19 epidemic.
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