Abstract

BackgroundAutism spectrum disorders (ASD) imply a spectrum of symptoms rather than a single phenotype. ASD could affect brain connectivity at different degree based on the severity of the symptom. Given their excellent learning capability, graph neural networks (GNN) methods have recently been used to uncover functional connectivity patterns and biological mechanisms in neuropsychiatric disorders, such as ASD. However, there remain challenges to develop an accurate GNN learning model and understand how specific decisions of these graph models are made in brain network analysis.ResultsIn this paper, we propose a graph attention network based learning and interpreting method, namely GAT-LI, which learns to classify functional brain networks of ASD individuals versus healthy controls (HC), and interprets the learned graph model with feature importance. Specifically, GAT-LI includes a graph learning stage and an interpreting stage. First, in the graph learning stage, a new graph attention network model, namely GAT2, uses graph attention layers to learn the node representation, and a novel attention pooling layer to obtain the graph representation for functional brain network classification. We experimentally compared GAT2 model’s performance on the ABIDE I database from 1035 subjects against the classification performances of other well-known models, and the results showed that the GAT2 model achieved the best classification performance. We experimentally compared the influence of different construction methods of brain networks in GAT2 model. We also used a larger synthetic graph dataset with 4000 samples to validate the utility and power of GAT2 model. Second, in the interpreting stage, we used GNNExplainer to interpret learned GAT2 model with feature importance. We experimentally compared GNNExplainer with two well-known interpretation methods including Saliency Map and DeepLIFT to interpret the learned model, and the results showed GNNExplainer achieved the best interpretation performance. We further used the interpretation method to identify the features that contributed most in classifying ASD versus HC.ConclusionWe propose a two-stage learning and interpreting method GAT-LI to classify functional brain networks and interpret the feature importance in the graph model. The method should also be useful in the classification and interpretation tasks for graph data from other biomedical scenarios.

Highlights

  • Autism spectrum disorders (ASD) imply a spectrum of symptoms rather than a single phenotype

  • The superior performance of GAT2 model in classifying functional brain networks stems from two key aspects of the graph neural networks: graph attention learning layers for node representation, and attention learning in graph pooling

  • For the construction of the brain network, we found that compared with the Anatomical Labeling (AAL) atlas, GAT2 using Harvard Oxford (HO) atlas can capture the functional differences between the brain networks of ASD and healthy controls (HC) in this dataset

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Summary

Introduction

Autism spectrum disorders (ASD) imply a spectrum of symptoms rather than a single phenotype. ASD could affect brain connectivity at different degree based on the severity of the symptom. Given their excellent learning capability, graph neural networks (GNN) methods have recently been used to uncover functional connectivity patterns and biological mechanisms in neuropsychiatric disorders, such as ASD. Brain functional connectivity of ASD individuals could be affected at different degree based on the severity of the symptom. Functional connectivity vectors are usually used as input data for deep learning models in classifying different phenotypes such as ASD versus healthy controls (HC) [2–7]. To further explore how specific decisions of these networks are made, some explanatory methods, such as piecewise linear neural networks [5], and Shapley value explanation [7], have recently been developed for deep learning models

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