36 research outputs found

    Predicting Hypertension Subtypes with Machine Learning Using Targeted Metabolites and Their Ratios

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    Hypertension is a major global health problem with high prevalence and complex associated health risks. Primary hypertension (PHT) is most common and the reasons behind primary hypertension are largely unknown. Endocrine hypertension (EHT) is another complex form of hypertension with an estimated prevalence varying from 3 to 20% depending on the population studied. It occurs due to underlying conditions associated with hormonal excess mainly related to adrenal tumours and sub-categorised: primary aldosteronism (PA), Cushing's syndrome (CS), pheochromocytoma or functional paraganglioma (PPGL). Endocrine hypertension is often misdiagnosed as primary hypertension, causing delays in treatment for the underlying condition, reduced quality of life, and costly antihypertensive treatment that is often ineffective. This study systematically used targeted metabolomics and high-throughput machine learning methods to predict the key biomarkers in classifying and distinguishing the various subtypes of endocrine and primary hypertension. The trained models successfully classified CS from PHT and EHT from PHT with 92% specificity on the test set. The most prominent targeted metabolites and metabolite ratios for hypertension identification for different disease comparisons were C18:1, C18:2, and Orn/Arg. Sex was identified as an important feature in CS vs. PHT classification

    Whole blood methylome-derived features to discriminate endocrine hypertension

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    BACKGROUND Arterial hypertension represents a worldwide health burden and a major risk factor for cardiovascular morbidity and mortality. Hypertension can be primary (primary hypertension, PHT), or secondary to endocrine disorders (endocrine hypertension, EHT), such as Cushing's syndrome (CS), primary aldosteronism (PA), and pheochromocytoma/paraganglioma (PPGL). Diagnosis of EHT is currently based on hormone assays. Efficient detection remains challenging, but is crucial to properly orientate patients for diagnostic confirmation and specific treatment. More accurate biomarkers would help in the diagnostic pathway. We hypothesized that each type of endocrine hypertension could be associated with a specific blood DNA methylation signature, which could be used for disease discrimination. To identify such markers, we aimed at exploring the methylome profiles in a cohort of 255 patients with hypertension, either PHT (n = 42) or EHT (n = 213), and at identifying specific discriminating signatures using machine learning approaches. RESULTS Unsupervised classification of samples showed discrimination of PHT from EHT. CS patients clustered separately from all other patients, whereas PA and PPGL showed an overall overlap. Global methylation was decreased in the CS group compared to PHT. Supervised comparison with PHT identified differentially methylated CpG sites for each type of endocrine hypertension, showing a diffuse genomic location. Among the most differentially methylated genes, FKBP5 was identified in the CS group. Using four different machine learning methods-Lasso (Least Absolute Shrinkage and Selection Operator), Logistic Regression, Random Forest, and Support Vector Machine-predictive models for each type of endocrine hypertension were built on training cohorts (80% of samples for each hypertension type) and estimated on validation cohorts (20% of samples for each hypertension type). Balanced accuracies ranged from 0.55 to 0.74 for predicting EHT, 0.85 to 0.95 for predicting CS, 0.66 to 0.88 for predicting PA, and 0.70 to 0.83 for predicting PPGL. CONCLUSIONS The blood DNA methylome can discriminate endocrine hypertension, with methylation signatures for each type of endocrine disorder

    Efficient Image Registration using Fast Principal Component Analysis

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    Incorporating spatial features with mutual information (MI) has demonstrated superior image registration performance compared with traditional MI-based methods, particularly in the presence of noise and intensity non-uniformities (INU). This paper presents a new efficient MI-based similarity measure which applies Expectation Maximisation for Principal Component Analysis (EMPCA-MI), to afford significantly lower computational complexity, while providing analogous image registration performance with other feature-based MI solutions. Experimental analysis corroborates both the improved robustness and faster runtimes of EMPCA-MI, for different test datasets containing both INU and noise artefacts

    Multimodal retinal image registration using a fast principal component analysis hybrid-based similarity measure

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    Multimodal retinal images (RI) are extensively used for analysing various eye diseases and conditions such as myopia and diabetic retinopathy. The incorporation of either two or more RI modalities provides complementary structure information in the presence of non-uniform illumination and low-contrast homogeneous regions. It also presents significant challenges for retinal image registration (RIR). This paper investigates how the Expectation Maximization for Principal Component Analysis with Mutual Information (EMPCA-MI) algorithm can effectively achieve multimodal RIR. This iterative hybrid-based similarity measure combines spatial features with mutual information to provide enhanced registration without recourse to either segmentation or feature extraction. Experimental results for clinical multimodal RI datasets comprising colour fundus and scanning laser ophthalmoscope images confirm EMPCA-MI is able to consistently afford superior numerical and qualitative registration performance compared with existing RIR techniques, such as the bifurcation structures method

    Why finance professors should be teaching Nietzsche

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    <p><strong>Abstract:</strong> Retinal images (RI) are widely used to diagnose a variety of eye conditions and diseases such as myopia and diabetic retinopathy. They are inherently characterised by having nonuniform illumination and low-contrast homogeneous regions which represent a unique set of challenges for retinal image registration (RIR). This paper investigates using the expectation maximization for principal component analysis based mutual information (EMPCA-MI) algorithm in RIR. It combines spatial features with mutual information to efficiently achieve improved registration performance. Experimental results for mono-modal RI datasets verify that EMPCA-MI<br>together with Powell-Brent optimization affords superior robustness in comparison with existing RIR methods, including the geometrical features method.</p> <p><br><strong>Index Terms</strong>— Image registration, principal component analysis, mutual information, expectation-maximization algorithms, retinopathy.</p> <p> </p> <p><strong>Poster presented at</strong>: 38th International Conference on Acoustics, Speech, and Signal Processing<br>(ICASSP), 26th to 31st May 2013, Vancouver, Canada.<br>doi: 10.1109/ICASSP.2013.6637824</p

    Targeted metabolomics as a tool in discriminating endocrine from primary hypertension

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    Context Identification of patients with endocrine forms of hypertension (EHT) (primary hyperaldosteronism [PA], pheochromocytoma/paraganglioma [PPGL], and Cushing syndrome [CS]) provides the basis to implement individualized therapeutic strategies. Targeted metabolomics (TM) have revealed promising results in profiling cardiovascular diseases and endocrine conditions associated with hypertension. Objective Use TM to identify distinct metabolic patterns between primary hypertension (PHT) and EHT and test its discriminating ability. Methods Retrospective analyses of PHT and EHT patients from a European multicenter study (ENSAT-HT). TM was performed on stored blood samples using liquid chromatography mass spectrometry. To identify discriminating metabolites a “classical approach” (CA) (performing a series of univariate and multivariate analyses) and a “machine learning approach” (MLA) (using random forest) were used. The study included 282 adult patients (52% female; mean age 49 years) with proven PHT (n = 59) and EHT (n = 223 with 40 CS, 107 PA, and 76 PPGL), respectively. Results From 155 metabolites eligible for statistical analyses, 31 were identified discriminating between PHT and EHT using the CA and 27 using the MLA, of which 16 metabolites (C9, C16, C16:1, C18:1, C18:2, arginine, aspartate, glutamate, ornithine, spermidine, lysoPCaC16:0, lysoPCaC20:4, lysoPCaC24:0, PCaeC42:0, SM C18:1, SM C20:2) were found by both approaches. The receiver operating characteristic curve built on the top 15 metabolites from the CA provided an area under the curve (AUC) of 0.86, which was similar to the performance of the 15 metabolites from MLA (AUC 0.83). Conclusion TM identifies distinct metabolic pattern between PHT and EHT providing promising discriminating performance
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