Predictive Clinical Neuroscience Portal (PCNportal): instant online access to research-grade normative models for clinical neuroscientists.

Abstract

The neurobiology of mental disorders remains poorly understood despite substantial scientific efforts, due to large clinical heterogeneity and to a lack of tools suitable to map individual variability. Normative modeling is one recently successful framework that can address these problems by comparing individuals to a reference population. The methodological underpinnings of normative modelling are, however, relatively complex and computationally expensive. Our research group has developed the python-based normative modelling package Predictive Clinical Neuroscience toolkit (PCNtoolkit) which provides access to many validated algorithms for normative modelling. PCNtoolkit has since proven to be a strong foundation for large scale normative modelling, but still requires significant computation power, time and technical expertise to develop. To address these problems, we introduce PCNportal. PCNportal is an online platform integrated with PCNtoolkit that offers access to pre-trained research-grade normative models estimated on tens of thousands of participants, without the need for computation power or programming abilities. PCNportal is an easy-to-use web interface that is highly scalable to large user bases as necessary. Finally, we demonstrate how the resulting normalized deviation scores can be used in a clinical application through a schizophrenia classification task applied to cortical thickness and volumetric data from the longitudinal Northwestern University Schizophrenia Data and Software Tool (NUSDAST) dataset. At each longitudinal timepoint, the transferred normative models achieved a mean[std. dev.] explained variance of 9.4[8.8]%, 9.2[9.2]%, 5.6[7.4]% respectively in the control group and 4.7[5.5]%, 6.0[6.2]%, 4.2[6.9]% in the schizophrenia group. Diagnostic classifiers achieved AUC of 0.78, 0.76 and 0.71 respectively. This replicates the utility of normative models for diagnostic classification of schizophrenia and showcases the use of PCNportal for clinical neuroimaging. By facilitating and speeding up research with high-quality normative models, this work contributes to research in inter-individual variability, clinical heterogeneity and precision medicine.