From phenotype to genotype in complex brain networks

• Published in: Scientific reports Vol. 6; no. 1; p. 19790
• Main Authors: Zanin, Massimiliano, Correia, Marco, Sousa, Pedro A. C., Cruz, Jorge
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22-01-2016; Nature Publishing Group
• Subjects: 631/378; 639/766/747; 9/10; Alzheimer Disease - genetics; Alzheimer Disease - pathology; Brain - pathology; Classification; Fitness; Genotype; Genotype & phenotype; Humanities and Social Sciences; Humans; Models, Neurological; multidisciplinary; Nerve Net - pathology; Nervous system; Neurological diseases; Phenotype; Probability; Reproducibility of Results; Science; Social organization
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep19790

Generative models are a popular instrument for illuminating the relationships between the hidden variables driving the growth of a complex network and its final topological characteristics, a process known as the “genotype to phenotype problem”. However, the definition of a complete methodology encompassing all stages of the analysis and in particular the validation of the final model, is still an open problem. We here discuss a framework that allows to quantitatively optimise and validate each step of the model creation process. It is based on the execution of a classification task and on estimating the additional precision provided by the modelled genotype. This encompasses the three main steps of the model creation, namely the selection of topological features, the optimisation of the parameters of the generative model and the validation of the obtained results. We provide a minimum requirement for a generative model to be useful, prescribing the function mapping genotype to phenotype to be non-monotonic; and we further show how a previously published model does not fulfil such condition, casting doubts on its fitness for the study of neurological disorders. The generality of such framework guarantees its applicability beyond neuroscience, like the emergence of social or technological networks.