Abstract
The O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and isocitrate dehydrogenase 1 (IDH1) mutation in high-grade gliomas (HGG) have proven to be the two important molecular indicators associated with better prognosis. Traditionally, the statuses of MGMT and IDH1 are obtained via surgical biopsy, which has limited their wider clinical implementation. Accurate presurgical prediction of their statuses based on preoperative multimodal neuroimaging is of great clinical value for a better treatment plan. Currently, the available data set associated with this study has several challenges, such as small sample size and complex, nonlinear (image) feature-to-(molecular) label relationship. To address these issues, we propose a novel multi-label nonlinear matrix completion (MNMC) model to jointly predict both MGMT and IDH1 statuses in a multi-task framework. Specifically, we first employ a nonlinear random Fourier feature mapping to improve the linear separability of the data, and then use transductive multi-task feature selection (performed in a nonlinearly transformed feature space) to refine the imputed soft labels, thus alleviating the overfitting problem caused by small sample size. We further design an optimization algorithm with a guaranteed convergence ability based on a block prox-linear method to solve the proposed MNMC model. Finally, by using a single-center, multimodal brain imaging and molecular pathology data set of HGG, we derive brain functional and structural connectomics features to jointly predict MGMT and IDH1 statuses. Results demonstrate that our proposed method outperforms the previously widely used single- and multi-task machine learning methods. This paper also shows the promise of utilizing brain connectomics for HGG prognosis in a non-invasive manner.