RESUMO
Comprehensive understanding of the human protein-protein interaction (PPI) network, aka the human interactome, can provide important insights into the molecular mechanisms of complex biological processes and diseases. Despite the remarkable experimental efforts undertaken to date to determine the structure of the human interactome, many PPIs remain unmapped. Computational approaches, especially network-based methods, can facilitate the identification of previously uncharacterized PPIs. Many such methods have been proposed. Yet, a systematic evaluation of existing network-based methods in predicting PPIs is still lacking. Here, we report community efforts initiated by the International Network Medicine Consortium to benchmark the ability of 26 representative network-based methods to predict PPIs across six different interactomes of four different organisms: A. thaliana, C. elegans, S. cerevisiae, and H. sapiens. Through extensive computational and experimental validations, we found that advanced similarity-based methods, which leverage the underlying network characteristics of PPIs, show superior performance over other general link prediction methods in the interactomes we considered.
Assuntos
Mapeamento de Interação de Proteínas , Saccharomyces cerevisiae , Animais , Humanos , Mapeamento de Interação de Proteínas/métodos , Caenorhabditis elegans , Mapas de Interação de Proteínas , Biologia Computacional/métodosRESUMO
Assessing the validity of a psychometric test is fundamental to ensure a reliable interpretation of its outcomes. Few attempts have been made recently to complement classical approaches (e.g., factor models) with a novel technique based on network analysis. The objective of the current study is to carry out a network-based validation of the Eating Disorder Inventory 3 (EDI-3), a questionnaire designed for the assessment of eating disorders. Exploiting a reliable, open source sample of 1206 patients diagnosed with an eating disorder, we set up a robust validation process encompassing detection and handling of redundant EDI-3 items, estimation of the cross-sample psychometric network, resampling bootstrap procedure and computation of the median network of the replica samples. We then employed a community detection algorithm to identify the topological clusters, evaluated their coherence with the EDI-3 subscales and replicated the full validation analysis on the subpopulations corresponding to patients diagnosed with either anorexia nervosa or bulimia nervosa. Results of the network-based analysis, and particularly the topological community structures, provided support for almost all the composite scores of the EDI-3 and for 2 single subscales: Bulimia and Maturity Fear. A moderate instability of some dimensions led to the identification of a few multidimensional items that should be better located in the intersection of multiple psychological scales. We also found that, besides symptoms typically attributed to eating disorders, such as drive for thinness, also non-specific symptoms like low self-esteem and interoceptive deficits play a central role in both the cross-sample and the diagnosis-specific networks. Our work adds insights into the complex and multidimensional structure of EDI-3 by providing support to its network-based validity on both mixed and diagnosis-specific samples. Moreover, we replicated previous results that reinforce the transdiagnostic theory of eating disorders.