Prediction of inhibitor development in previously untreated and minimally treated children with severe and moderately severe hemophilia A using a machine-learning network.

BACKGROUND: Prediction of inhibitor development in patients with hemophilia A (HA) remains a challenge. OBJECTIVES: To construct a predictive model for inhibitor development in HA using a network of clinical variables and biomarkers based on the individual similarity network. METHODS: Previously untreated and minimally treated children with severe/moderately severe HA, participants of the HEMFIL Cohort Study, were followed up until reaching 75 exposure days (EDs) without inhibitor (INH-) or upon inhibitor development (INH+). Clinical data and biological samples were collected before the start of factor (F)VIII replacement (T0). A predictive model (HemfilNET) was built to compare the networks and potential global topological differences between INH- and INH+ at T0, considering the network robustness. For validation, the "leave-one-out" cross-validation technique was employed. Accuracy, precision, recall, and F1-score were used as evaluation metrics for the machine-learning model. RESULTS: We included 95 children with HA (CHA), of whom 31 (33%) developed inhibitors. The algorithm, featuring 37 variables, identified distinct patterns of networks at T0 for INH+ and INH-. The accuracy of the model was 74.2% for CHA INH+ and 98.4% for INH-. By focusing the analysis on CHA with high-risk F8 mutations for inhibitor development, the accuracy in identifying CHA INH+ increased to 82.1%. CONCLUSION: Our machine-learning algorithm demonstrated an overall accuracy of 90.5% for predicting inhibitor development in CHA, which further improved when restricting the analysis to CHA with a high-risk F8 genotype. However, our model requires validation in other cohorts. Yet, missing data for some variables hindered more precise predictions.

Distinguishing noise from chaos: objective versus subjective criteria using horizontal visibility graph.

A recently proposed methodology called the Horizontal Visibility Graph (HVG) [Luque et al., Phys. Rev. E., 80, 046103 (2009)] that constitutes a geometrical simplification of the well known Visibility Graph algorithm [Lacasa et al., Proc. Natl. Sci. U.S.A. 105, 4972 (2008)], has been used to study the distinction between deterministic and stochastic components in time series [L. Lacasa and R. Toral, Phys. Rev. E., 82, 036120 (2010)]. Specifically, the authors propose that the node degree distribution of these processes follows an exponential functional of the form [Formula: see text], in which [Formula: see text] is the node degree and [Formula: see text] is a positive parameter able to distinguish between deterministic (chaotic) and stochastic (uncorrelated and correlated) dynamics. In this work, we investigate the characteristics of the node degree distributions constructed by using HVG, for time series corresponding to [Formula: see text] chaotic maps, 2 chaotic flows and [Formula: see text] different stochastic processes. We thoroughly study the methodology proposed by Lacasa and Toral finding several cases for which their hypothesis is not valid. We propose a methodology that uses the HVG together with Information Theory quantifiers. An extensive and careful analysis of the node degree distributions obtained by applying HVG allow us to conclude that the Fisher-Shannon information plane is a remarkable tool able to graphically represent the different nature, deterministic or stochastic, of the systems under study.

Simulating the dynamics of scale-free networks via optimization.

We deal here with the issue of complex network evolution. The analysis of topological evolution of complex networks plays a crucial role in predicting their future. While an impressive amount of work has been done on the issue, very little attention has been so far devoted to the investigation of how information theory quantifiers can be applied to characterize networks evolution. With the objective of dynamically capture the topological changes of a network's evolution, we propose a model able to quantify and reproduce several characteristics of a given network, by using the square root of the Jensen-Shannon divergence in combination with the mean degree and the clustering coefficient. To support our hypothesis, we test the model by copying the evolution of well-known models and real systems. The results show that the methodology was able to mimic the test-networks. By using this copycat model, the user is able to analyze the networks behavior over time, and also to conjecture about the main drivers of its evolution, also providing a framework to predict its evolution.