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.

Diffusion capacity of single and interconnected networks.

Understanding diffusive processes in networks is a significant challenge in complexity science. Networks possess a diffusive potential that depends on their topological configuration, but diffusion also relies on the process and initial conditions. This article presents Diffusion Capacity, a concept that measures a node's potential to diffuse information based on a distance distribution that considers both geodesic and weighted shortest paths and dynamical features of the diffusion process. Diffusion Capacity thoroughly describes the role of individual nodes during a diffusion process and can identify structural modifications that may improve diffusion mechanisms. The article defines Diffusion Capacity for interconnected networks and introduces Relative Gain, which compares the performance of a node in a single structure versus an interconnected one. The method applies to a global climate network constructed from surface air temperature data, revealing a significant change in diffusion capacity around the year 2000, suggesting a loss of the planet's diffusion capacity that could contribute to the emergence of more frequent climatic events.

Assessing diversity in multiplex networks.

Diversity, understood as the variety of different elements or configurations that an extensive system has, is a crucial property that allows maintaining the system's functionality in a changing environment, where failures, random events or malicious attacks are often unavoidable. Despite the relevance of preserving diversity in the context of ecology, biology, transport, finances, etc., the elements or configurations that more contribute to the diversity are often unknown, and thus, they can not be protected against failures or environmental crises. This is due to the fact that there is no generic framework that allows identifying which elements or configurations have crucial roles in preserving the diversity of the system. Existing methods treat the level of heterogeneity of a system as a measure of its diversity, being unsuitable when systems are composed of a large number of elements with different attributes and types of interactions. Besides, with limited resources, one needs to find the best preservation policy, i.e., one needs to solve an optimization problem. Here we aim to bridge this gap by developing a metric between labeled graphs to compute the diversity of the system, which allows identifying the most relevant components, based on their contribution to a global diversity value. The proposed framework is suitable for large multiplex structures, which are constituted by a set of elements represented as nodes, which have different types of interactions, represented as layers. The proposed method allows us to find, in a genetic network (HIV-1), the elements with the highest diversity values, while in a European airline network, we systematically identify the companies that maximize (and those that less compromise) the variety of options for routes connecting different airports.

Quantification of network structural dissimilarities.

Identifying and quantifying dissimilarities among graphs is a fundamental and challenging problem of practical importance in many fields of science. Current methods of network comparison are limited to extract only partial information or are computationally very demanding. Here we propose an efficient and precise measure for network comparison, which is based on quantifying differences among distance probability distributions extracted from the networks. Extensive experiments on synthetic and real-world networks show that this measure returns non-zero values only when the graphs are non-isomorphic. Most importantly, the measure proposed here can identify and quantify structural topological differences that have a practical impact on the information flow through the network, such as the presence or absence of critical links that connect or disconnect connected components.