The multicenter European Biological Variation Study (EuBIVAS): A new glance provided by the Principal Component Analysis (PCA), a machine learning unsupervised algorithms, based on the basic metabolic panel linked measurands

The European Biological Variation Study (EuBIVAS), which includes 91 healthy volunteers from five European countries, estimated high-quality biological variation (BV) data for several measurands. Previous EuBIVAS papers reported no significant differences among laboratories/population; however, they were focused on specific set of measurands, without a comprehensive general look. The aim of this paper is to evaluate the homogeneity of EuBIVAS data considering multivariate information applying the Principal Component Analysis (PCA), a machine learning unsupervised algorithm. The EuBIVAS data for 13 basic metabolic panel linked measurands (glucose, albumin, total protein, electrolytes, urea, total bilirubin, creatinine, phosphatase alkaline, aminotransferases), age, sex, menopause, body mass index (BMI), country, alcohol, smoking habits, and physical activity, have been used to generate three databases developed using the traditional univariate and the multivariate Elliptic Envelope approaches to detect outliers, and different missing-value imputations. Two matrix of data for each database, reporting both mean values, and "within-person BV"(CVP) values for any measurand/subject, were analyzed using PCA. A clear clustering between males and females mean values has been identified, where the menopausal females are closer to the males. Data interpretations for the three databases are similar. No significant differences for both mean and CVPs values, for countries, alcohol, smoking habits, BMI and physical activity, have been found. The absence of meaningful differences among countries confirms the EuBIVAS sample homogeneity and that the obtained data are widely applicable to deliver APS. Our data suggest that the use of PCA and the multivariate approach may be used to detect outliers, although further studies are required.