Extracting brain disease‐related connectome subgraphs by adaptive dense subgraph discovery

Group‐level brain connectome analysis has attracted increasing interest in neuropsychiatric research with the goal of identifying connectomic subnetworks (subgraphs) that are systematically associated with brain disorders. However, extracting disease‐related subnetworks from the whole brain connectome has been challenging, because no prior knowledge is available regarding the sizes and locations of the subnetworks. In addition, neuroimaging data are often mixed with substantial noise that can further obscure informative subnetwork detection. We propose a likelihood‐based adaptive dense subgraph discovery (ADSD) model to extract disease‐related subgraphs from the group‐level whole brain connectome data. Our method is robust to both false positive and false negative errors of edge‐wise inference and thus can lead to a more accurate discovery of latent disease‐related connectomic subnetworks. We develop computationally efficient algorithms to implement the novel ADSD objective function and derive theoretical results to guarantee the convergence properties. We apply the proposed approach to a brain fMRI study for schizophrenia research and identify well‐organized and biologically meaningful subnetworks that exhibit schizophrenia‐related salience network centered connectivity abnormality. Analysis of synthetic data also demonstrates the superior performance of the ADSD method for latent subnetwork detection in comparison with existing methods in various settings.