Nobiletin as a chemopreventive natural product against cancer, a comprehensive review.

As a leading cause of death, second only to heart disease, cancer has always been one of the burning topics in medical research. When targeting multiple signal pathways in tumorigenesis chemoprevention, using natural or synthetic anti-cancer drugs is a vital strategy to reduce cancer damage. However, toxic effects, multidrug resistance (MDR) as well as cancer stem cells (CSCs) all prominently limited the clinical application of conventional anticancer drugs. With low side effects, strong biological activity, unique mechanism, and wide range of targets, natural products derived from plants are considered significant sources for new drug development. Nobiletin is one of the most attractive compounds, a unique flavonoid primarily isolated from the peel of citrus fruits. Numerous studies in vitro and in vivo have suggested that nobiletin and its derivatives possess the eminent potential to become effective cancer chemoprevention agents through various cellular and molecular levels. This article aims to comprehensively review the anticancer efficacy and specific mechanisms of nobiletin, enhancing our understanding of its chemoprevention properties and providing the latest research findings. At the end of this review, we also give some discussion and future perspectives regarding the challenges and opportunities in nobiletin efficient exploitation.

Citrus flavonoids and their antioxidant evaluation.

The antioxidant ability is the link and bridge connecting a variety of biological activities. Citrus flavonoids play an essential role in regulating oxidative stress and are an important source of daily intake of antioxidant supplements. Many studies have shown that citrus flavonoids promote health through antioxidation. In this review, the biosynthesis, composition and distribution of citrus flavonoids were concluded. The detection methods of antioxidant capacity of citrus flavonoids were divided into four categories: chemical, cellular, animal and clinical antioxidant capacity evaluation systems. The modeling methods, applicable scenarios, and their relative merits were compared based on these four systems. The antioxidant functions of citrus flavonoids under different evaluation systems were also discussed, especially the regulation of the Nrf2-antioxidases pathway. Some shortcomings in the current research were pointed out, and some suggestions for progress were put forward.

Manifold regularized multitask feature learning for multimodality disease classification.

Multimodality based methods have shown great advantages in classification of Alzheimer's disease (AD) and its prodromal stage, that is, mild cognitive impairment (MCI). Recently, multitask feature selection methods are typically used for joint selection of common features across multiple modalities. However, one disadvantage of existing multimodality based methods is that they ignore the useful data distribution information in each modality, which is essential for subsequent classification. Accordingly, in this paper we propose a manifold regularized multitask feature learning method to preserve both the intrinsic relatedness among multiple modalities of data and the data distribution information in each modality. Specifically, we denote the feature learning on each modality as a single task, and use group-sparsity regularizer to capture the intrinsic relatedness among multiple tasks (i.e., modalities) and jointly select the common features from multiple tasks. Furthermore, we introduce a new manifold-based Laplacian regularizer to preserve the data distribution information from each task. Finally, we use the multikernel support vector machine method to fuse multimodality data for eventual classification. Conversely, we also extend our method to the semisupervised setting, where only partial data are labeled. We evaluate our method using the baseline magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG-PET), and cerebrospinal fluid (CSF) data of subjects from AD neuroimaging initiative database. The experimental results demonstrate that our proposed method can not only achieve improved classification performance, but also help to discover the disease-related brain regions useful for disease diagnosis.

Topological graph kernel on multiple thresholded functional connectivity networks for mild cognitive impairment classification.

Recently, brain connectivity networks have been used for classification of Alzheimer's disease and mild cognitive impairment (MCI) from normal controls (NC). In typical connectivity-networks-based classification approaches, local measures of connectivity networks are first extracted from each region-of-interest as network features, which are then concatenated into a vector for subsequent feature selection and classification. However, some useful structural information of network, especially global topological information, may be lost in this type of approaches. To address this issue, in this article, we propose a connectivity-networks-based classification framework to identify accurately the MCI patients from NC. The core of the proposed method involves the use of a new graph-kernel-based approach to measure directly the topological similarity between connectivity networks. We evaluate our method on functional connectivity networks of 12 MCI and 25 NC subjects. The experimental results show that our proposed method achieves a classification accuracy of 91.9%, a sensitivity of 100.0%, a balanced accuracy of 94.0%, and an area under receiver operating characteristic curve of 0.94, demonstrating a great potential in MCI classification, based on connectivity networks. Further connectivity analysis indicates that the connectivity of the selected brain regions is different between MCI patients and NC, that is, MCI patients show reduced functional connectivity compared with NC, in line with the findings reported in the existing studies.

LCGNet: Local Sequential Feature Coupling Global Representation Learning for Functional Connectivity Network Analysis with fMRI.

Analysis of functional connectivity networks (FCNs) derived from resting-state functional magnetic resonance imaging (rs-fMRI) has greatly advanced our understanding of brain diseases, including Alzheimer's disease (AD) and attention deficit hyperactivity disorder (ADHD). Advanced machine learning techniques, such as convolutional neural networks (CNNs), have been used to learn high-level feature representations of FCNs for automated brain disease classification. Even though convolution operations in CNNs are good at extracting local properties of FCNs, they generally cannot well capture global temporal representations of FCNs. Recently, the transformer technique has demonstrated remarkable performance in various tasks, which is attributed to its effective self-attention mechanism in capturing the global temporal feature representations. However, it cannot effectively model the local network characteristics of FCNs. To this end, in this paper, we propose a novel network structure for Local sequential feature Coupling Global representation learning (LCGNet) to take advantage of convolutional operations and self-attention mechanisms for enhanced FCN representation learning. Specifically, we first build a dynamic FCN for each subject using an overlapped sliding window approach. We then construct three sequential components (i.e., edge-to-vertex layer, vertex-to-network layer, and network-to-temporality layer) with a dual backbone branch of CNN and transformer to extract and couple from local to global topological information of brain networks. Experimental results on two real datasets (i.e., ADNI and ADHD-200) with rs-fMRI data show the superiority of our LCGNet.

Identification of high-functioning autism spectrum disorders based on gray-white matter functional network connectivity.

In the field of autism spectrum disorder (ASD), research on functional connectivity between gray matter and white matter remains under-researched. To address this gap, this study innovatively introduced a nested cross-validation method that integrates gray-white matter functional connectivity with an F-Score algorithm. This method calculates the correlation based on signals extracted from functional magnetic resonance imaging data using gray matter and white matter brain region templates. After applying the method to a New York University Langone Medical Center dataset consisting of 55 individuals with high-functioning ASD and 52 healthy subjects, we achieved a classification accuracy of 72.94%. This study found abnormal functional connectivity, primarily involving the left anterior prefrontal cortex and right superior corona radiata, left retrosplenial cortex and left superior corona radiata, as well as the left ventral anterior cingulate cortex and body of corpus callosum. Besides, we discovered that these abnormal connections are closely related to social impairment and restrictive and repetitive behaviors in ASD. In conclusion, this study provides a gray-white matter functional connectivity perspective for the diagnosis and understanding of ASD.

Distribution-Guided Network Thresholding for Functional Connectivity Analysis in fMRI-Based Brain Disorder Identification.

Functional connectivity (FC) networks derived from resting-state functional magnetic resonance imaging (rs-fMRI) have been widely used in automated identification of brain disorders, such as Alzheimer's disease (AD) and attention deficit hyperactivity disorder (ADHD). To generate compact representations of FC networks, various thresholding methods have been designed for FC network analysis. However, these studies usually use a pre-defined threshold or connection percentage to threshold whole FC networks, thus ignoring the diversity of temporal correlation (e.g., strong associations) between brain regions in subject groups. In this work, we propose a distribution-guided network thresholding learning (DNTL) method for FC network analysis in brain disorder identification with rs-fMRI. Specifically, for each connection of a pair of brain regions, we propose to determine its specific threshold based on the distribution of connection strength (i.e., temporal correlation) between subject groups (e.g., patients and normal controls). The proposed DNTL can adaptively yield an FC-specific threshold for each connection in an FC network, thus preserving diversity of temporal correlation among different brain regions. Experiment results on 365 subjects from two datasets (i.e., ADNI and ADHD-200) suggest that the DNT method outperforms state-of-the-art methods in brain disorder identification with rs-fMRI data.

Convolutional Recurrent Neural Network for Dynamic Functional MRI Analysis and Brain Disease Identification.

Dynamic functional connectivity (dFC) networks derived from resting-state functional magnetic resonance imaging (rs-fMRI) help us understand fundamental dynamic characteristics of human brains, thereby providing an efficient solution for automated identification of brain diseases, such as Alzheimer's disease (AD) and its prodromal stage. Existing studies have applied deep learning methods to dFC network analysis and achieved good performance compared with traditional machine learning methods. However, they seldom take advantage of sequential information conveyed in dFC networks that could be informative to improve the diagnosis performance. In this paper, we propose a convolutional recurrent neural network (CRNN) for automated brain disease classification with rs-fMRI data. Specifically, we first construct dFC networks from rs-fMRI data using a sliding window strategy. Then, we employ three convolutional layers and long short-term memory (LSTM) layer to extract high-level features of dFC networks and also preserve the sequential information of extracted features, followed by three fully connected layers for brain disease classification. Experimental results on 174 subjects with 563 rs-fMRI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) demonstrate the effectiveness of our proposed method in binary and multi-category classification tasks.

An Immuno-Separated Assay for Ochratoxin Detection Coupled with a Nano-Affinity Cleaning-Up for LC-Confirmation.

An immuno-separated assay for ochratoxin A detection coupled with a nano-affinity cleaning up for LC-confirmation was developed. Firstly, ochratoxin A was modified to quantum dot beads for immuno-fluorescent reporters. Secondly, Fe3O4 magnetic nanoparticles were conjugated with protein G for immuno-magnetic adsorbents. The immuno-separation of fluorescent reporters by magnetic adsorbents could be completed by ochratoxin A, so the fluorescent reporters released from the immune complex indicate a linear correlation with the concentration of ochratoxin A. Furthermore, the immuno-separated ochratoxin A can be eluted from magnetic adsorbent for LC-conformation. The optimized assay showed results as follows: the quantitative range of the immuno-separated assay was 0.03-100 ng mL-1 of ochratoxin A. The recoveries for spiked samples ranged from 78.2% to 91.4%, with the relative standard deviation (RSD) being 11.9%~15.3%. Statistical analysis indicated no significant difference between the HPLC-FLD results based on commercial affinity column and by nano-affinity cleaning up.

A novel node-level structure embedding and alignment representation of structural networks for brain disease analysis.

Brain networks based on various neuroimaging technologies, such as diffusion tensor image (DTI) and functional magnetic resonance imaging (fMRI), have been widely applied to brain disease analysis. Currently, there are several node-level structural measures (e.g., local clustering coefficients and node degrees) for representing and analyzing brain networks since they usually can reflect the topological structure of brain regions. However, these measures typically describe specific types of structural information, ignoring important network properties (i.e., small structural changes) that could further improve the performance of brain network analysis. To overcome this problem, in this paper, we first define a novel node-level structure embedding and alignment (nSEA) representation to accurately characterize the node-level structural information of the brain network. Different from existing measures that characterize a specific type of structural properties with a single value, our proposed nSEA method can learn a vector representation for each node, thus contain richer structure information to capture small structural changes. Furthermore, we develop an nSEA representation based learning (nSEAL) framework for brain disease analysis. Specifically, we first perform structural embedding to calculate node vector representations for each brain network and then align vector representations of all brain networks into the common space for two group-level network analyses, including a statistical analysis and brain disease classifications. Experiment results on a real schizophrenia dataset demonstrate that our proposed method not only discover disease-related brain regions that could help to better understand the pathology of brain diseases, but also improve the classification performance of brain diseases, compared with state-of-the-art methods.

Designing weighted correlation kernels in convolutional neural networks for functional connectivity based brain disease diagnosis.

Functional connectivity networks (FCNs) based on functional magnetic resonance imaging (fMRI) have been widely applied to analyzing and diagnosing brain diseases, such as Alzheimer's disease (AD) and its prodrome stage, i.e., mild cognitive impairment (MCI). Existing studies usually use Pearson correlation coefficient (PCC) method to construct FCNs, and then extract network measures (e.g., clustering coefficients) as features to learn a diagnostic model. However, the valuable observation information in network construction (e.g., specific contributions of different time points), as well as high-level and high-order network features are neglected in these studies. In this paper, we first define a novel weighted correlation kernel (called wc-kernel) to measure the correlation of brain regions, by which weighting factors are learned in a data-driven manner to characterize the contributions of different time points, thus conveying the richer interaction information among brain regions compared with the PCC method. Furthermore, we build a wc-kernel based convolutional neural network (CNN) (called wck-CNN) framework for learning the hierarchical (i.e., from local to global and also from low-level to high-level) features for disease diagnosis, by using fMRI data. Specifically, we first define a layer to build dynamic FCNs using our proposed wc-kernels. Then, we define another three layers to sequentially extract local (brain region specific), global (brain network specific) and temporal features from the constructed dynamic FCNs for classification. Experimental results on 174 subjects (a total of 563 scans) with rest-state fMRI (rs-fMRI) data from ADNI database demonstrate the efficacy of our proposed method.

Multimodal hyper-connectivity of functional networks using functionally-weighted LASSO for MCI classification.

Recent works have shown that hyper-networks derived from blood-oxygen-level-dependent (BOLD) fMRI, where an edge (called hyper-edge) can be connected to more than two nodes, are effective biomarkers for MCI classification. Although BOLD fMRI is a high temporal resolution fMRI approach to assess alterations in brain networks, it cannot pinpoint to a single correlation of neuronal activity since BOLD signals are composite. In contrast, arterial spin labeling (ASL) is a lower temporal resolution fMRI technique for measuring cerebral blood flow (CBF) that can provide quantitative, direct brain network physiology measurements. This paper proposes a novel sparse regression algorithm for inference of the integrated hyper-connectivity networks from BOLD fMRI and ASL fMRI. Specifically, a least absolution shrinkage and selection operator (LASSO) algorithm, which is constrained by the functional connectivity derived from ASL fMRI, is employed to estimate hyper-connectivity for characterizing BOLD-fMRI-based functional interaction among multiple regions. An ASL-derived functional connectivity is constructed by using an Ultra-GroupLASSO-UOLS algorithm, where the combination of ultra-least squares (ULS) criterion with a group LASSO (GroupLASSO) algorithm is applied to detect the topology of ASL-based functional connectivity networks, and then an ultra-orthogonal least squares (UOLS) algorithm is used to estimate the connectivity strength. By combining the complementary characterization conveyed by rs-fMRI and ASL fMRI, our multimodal hyper-networks demonstrated much better discriminative characteristics than either the conventional pairwise connectivity networks or the unimodal hyper-connectivity networks. Experimental results on publicly available ADNI dataset demonstrate that the proposed method outperforms the existing single modality based sparse functional connectivity inference methods.

Integration of temporal and spatial properties of dynamic connectivity networks for automatic diagnosis of brain disease.

Functional connectivity networks (FCNs) using resting-state functional magnetic resonance imaging (rs-fMRI) have been applied to the analysis and diagnosis of brain disease, such as Alzheimer's disease (AD) and its prodrome, i.e., mild cognitive impairment (MCI). Different from conventional studies focusing on static descriptions on functional connectivity (FC) between brain regions in rs-fMRI, recent studies have resorted to dynamic connectivity networks (DCNs) to characterize the dynamic changes of FC, since dynamic changes of FC may indicate changes in macroscopic neural activity patterns in cognitive and behavioral aspects. However, most of the existing studies only investigate the temporal properties of DCNs (e.g., temporal variability of FC between specific brain regions), ignoring the important spatial properties of the network (e.g., spatial variability of FC associated with a specific brain region). Also, emerging evidence on FCNs has suggested that, besides temporal variability, there is significant spatial variability of activity foci over time. Hence, integrating both temporal and spatial properties of DCNs can intuitively promote the performance of connectivity-network-based learning methods. In this paper, we first define a new measure to characterize the spatial variability of DCNs, and then propose a novel learning framework to integrate both temporal and spatial variabilities of DCNs for automatic brain disease diagnosis. Specifically, we first construct DCNs from the rs-fMRI time series at successive non-overlapping time windows. Then, we characterize the spatial variability of a specific brain region by computing the correlation of functional sequences (i.e., the changing profile of FC between a pair of brain regions within all time windows) associated with this region. Furthermore, we extract both temporal variabilities and spatial variabilities from DCNs as features, and integrate them for classification by using manifold regularized multi-task feature learning and multi-kernel learning techniques. Results on 149 subjects with baseline rs-fMRI data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) suggest that our method can not only improve the classification performance in comparison with state-of-the-art methods, but also provide insights into the spatio-temporal interaction patterns of brain activity and their changes in brain disorders.

Sub-Network Kernels for Measuring Similarity of Brain Connectivity Networks in Disease Diagnosis.

As a simple representation of interactions among distributed brain regions, brain networks have been widely applied to automated diagnosis of brain diseases, such as Alzheimer's disease (AD) and its early stage, i.e., mild cognitive impairment (MCI). In brain network analysis, a challenging task is how to measure the similarity between a pair of networks. Although many graph kernels (i.e., kernels defined on graphs) have been proposed for measuring the topological similarity of a pair of brain networks, most of them are defined using general graphs, thus ignoring the uniqueness of each node in brain networks. That is, each node in a brain network denotes a particular brain region, which is a specific characteristics of brain networks. Accordingly, in this paper, we construct a novel sub-network kernel for measuring the similarity between a pair of brain networks and then apply it to brain disease classification. Different from current graph kernels, our proposed sub-network kernel not only takes into account the inherent characteristic of brain networks, but also captures multi-level (from local to global) topological properties of nodes in brain networks, which are essential for defining the similarity measure of brain networks. To validate the efficacy of our method, we perform extensive experiments on subjects with baseline functional magnetic resonance imaging data obtained from the Alzheimer's disease neuroimaging initiative database. Experimental results demonstrate that the proposed method outperforms several state-of-the-art graph-based methods in MCI classification.

Ordinal Pattern: A New Descriptor for Brain Connectivity Networks.

Brain connectivity networks based on magnetic resonance imaging (MRI) or functional MRI (fMRI) data provide a straightforward way to quantify the structural or functional systems of the brain. Currently, there are several network descriptors developed for representing and analyzing brain connectivity networks. However, most of them are designed for unweighted networks, regardless of the valuable weight information of edges, or do not take advantage of the ordinal relationship of weighted edges (even though they are designed for weighted networks). In this paper, we propose a new network descriptor (i.e., ordinal pattern that contains a sequence of weighted edges) for brain connectivity network analysis. Compared with previous network properties, the proposed ordinal patterns cannot only take advantage of the weight information of edges but also explicitly model the ordinal relationship of weighted edges in brain connectivity networks. We further develop an ordinal pattern-based learning framework for brain disease diagnosis using resting-state fMRI data. Specifically, we first construct a set of brain functional connectivity networks, where each network is corresponding to a particular subject. We then develop an algorithm to identify ordinal patterns that frequently appear in brain connectivity networks of patients and normal controls. We further perform discriminative ordinal pattern selection and extract feature representations for subjects based on the selected ordinal patterns, followed by a learning model for automated brain disease diagnosis. Experimental results on both Alzheimer's Disease Neuroimaging Initiative and attention deficit hyperactivity disorder-200 data sets demonstrate that our method outperforms the several state-of-the-art approaches in the tasks of disease classification and clinical score regression.

Developing Novel Weighted Correlation Kernels for Convolutional Neural Networks to Extract Hierarchical Functional Connectivities from fMRI for Disease Diagnosis.

Functional magnetic resonance imaging (fMRI) has been widely applied to analysis and diagnosis of brain diseases, including Alzheimer's disease (AD) and its prodrome, i.e., mild cognitive impairment (MCI). Traditional methods usually construct connectivity networks (CNs) by simply calculating Pearson correlation coefficients (PCCs) between time series of brain regions, and then extract low-level network measures as features to train the learning model. However, the valuable observation information in network construction (e.g., specific contributions of different time points) and high-level (i.e., high-order) network properties are neglected in these methods. In this paper, we first define a novel weighted correlation kernel (called wc-kernel) to measure the correlation of brain regions, by which weighting factors are determined in a data-driven manner to characterize the contribution of each time point, thus conveying the richer interaction information of brain regions compared with the PCC method. Furthermore, we propose a wc-kernel based convolutional neural network (CNN) (called wck-CNN) framework for extracting the hierarchical (i.e., from low-order to high-order) functional connectivities for disease diagnosis, by using fMRI data. Specifically, we first define a layer to build dynamic CNs (DCNs) using the defined wc-kernels. Then, we define three layers to extract local (region specific), global (network specific) and temporal high-order properties from the constructed low-order functional connectivities as features for classification. Results on 174 subjects (a total of 563 scans) with rs-fMRI data from ADNI suggest that the our method can not only improve the performance compared with state-of-the-art methods, but also provide novel insights into the interaction patterns of brain activities and their changes in diseases.

Subnetwork mining on functional connectivity network for classification of minimal hepatic encephalopathy.

Hepatic encephalopathy (HE), as a complication of cirrhosis, is a serious brain disease, which may lead to death. Accurate diagnosis of HE and its intermediate stage, i.e., minimal HE (MHE), is very important for possibly early diagnosis and treatment. Brain connectivity network, as a simple representation of brain interaction, has been widely used for the brain disease (e.g., HE and MHE) analysis. However, those studies mainly focus on finding disease-related abnormal connectivity between brain regions, although a large number of studies have indicated that some brain diseases are usually related to local structure of brain connectivity network (i.e., subnetwork), rather than solely on some single brain regions or connectivities. Also, mining such disease-related subnetwork is a challenging task because of the complexity of brain network. To address this problem, we proposed a novel frequent-subnetwork-based method to mine disease-related subnetworks for MHE classification. Specifically, we first mine frequent subnetworks from both groups, i.e., MHE patients and non-HE (NHE) patients, respectively. Then we used the graph-kernel based method to select the most discriminative subnetworks for subsequent classification. We evaluate our proposed method on a MHE dataset with 77 cirrhosis patients, including 38 MHE patients and 39 NHE patients. The results demonstrate that our proposed method can not only obtain the improved classification performance in comparison with state-of-the-art network-based methods, but also identify disease-related subnetworks which can help us better understand the pathology of the brain diseases.

Temporally Constrained Group Sparse Learning for Longitudinal Data Analysis in Alzheimer's Disease.

Sparse learning has been widely investigated for analysis of brain images to assist the diagnosis of Alzheimer's disease and its prodromal stage, i.e., mild cognitive impairment. However, most existing sparse learning-based studies only adopt cross-sectional analysis methods, where the sparse model is learned using data from a single time-point. Actually, multiple time-points of data are often available in brain imaging applications, which can be used in some longitudinal analysis methods to better uncover the disease progression patterns. Accordingly, in this paper, we propose a novel temporallyconstrained group sparse learning method aiming for longitudinal analysis with multiple time-points of data. Specifically, we learn a sparse linear regression model by using the imaging data from multiple time-points, where a group regularization term is first employed to group the weights for the same brain region across different time-points together. Furthermore, to reflect the smooth changes between data derived from adjacent time-points, we incorporate two smoothness regularization terms into the objective function, i.e., one fused smoothness term thatrequires that the differences between two successive weight vectors from adjacent time-points should be small, and another output smoothness term thatrequires the differences between outputs of two successive models from adjacent time-points should also be small. We develop an efficient optimization algorithm to solve the proposed objective function. Experimental results on ADNI database demonstrate that, compared with conventional sparse learning-based methods, our proposed method can achieve improved regression performance and also help in discovering disease-related biomarkers.

Multimodal Hyper-connectivity Networks for MCI Classification.

Hyper-connectivity network is a network where every edge is connected to more than two nodes, and can be naturally denoted using a hyper-graph. Hyper-connectivity brain network, either based on structural or functional interactions among the brain regions, has been used for brain disease diagnosis. However, the conventional hyper-connectivity network is constructed solely based on single modality data, ignoring potential complementary information conveyed by other modalities. The integration of complementary information from multiple modalities has been shown to provide a more comprehensive representation about the brain disruptions. In this paper, a novel multimodal hyper-network modelling method was proposed for improving the diagnostic accuracy of mild cognitive impairment (MCI). Specifically, we first constructed a multimodal hyper-connectivity network by simultaneously considering information from diffusion tensor imaging and resting-state functional magnetic resonance imaging data. We then extracted different types of network features from the hyper-connectivity network, and further exploited a manifold regularized multi-task feature selection method to jointly select the most discriminative features. Our proposed multimodal hyper-connectivity network demonstrated a better MCI classification performance than the conventional single modality based hyper-connectivity networks.

Network-based classification of ADHD patients using discriminative subnetwork selection and graph kernel PCA.

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most prevalent behavioral disorders in childhood and adolescence. Recently, network-based diagnosis of ADHD has attracted great attentions due to the fact that ADHD disease is related to not only individual brain regions but also the connections among them, while existing methods are hard to discover disorder patterns related with several brain regions. NEW METHOD: To overcome this drawback, a discriminative subnetwork selection method is proposed to directly mine those frequent and discriminative subnetworks from the whole brain networks of ADHD and normal control (NC) groups. Then, the graph kernel principal component (PCA) is applied to extract features from those discriminative subnetworks. Finally, support vector machine (SVM) is adopted for classification of ADHD and NC subjects. RESULTS: We evaluate the performances of our proposed method using the ADHD200 dataset, which contains 118 ADHD patients and 98 normal controls. The experimental results show that our proposed method can achieve a very high accuracy of 94.91% for ADHD vs. NC classification. Moreover, our proposed method can also discover the discriminative subnetworks as well as the discriminative brain regions, which are helpful for enhancing our understanding of ADHD disease. COMPARISON WITH EXISTING METHOD(S): The accuracy of our proposed method is 9.20% higher than those of the state-of-the-art methods. CONCLUSIONS: A lot of experiments in ADHD200 dataset show that, our proposed method can improve the performance significantly comparing to the state-of-the-art methods.