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通过稀疏多模态多任务学习从多维异质成像遗传学数据中识别疾病敏感和定量性状相关生物标志物。

Identifying disease sensitive and quantitative trait-relevant biomarkers from multidimensional heterogeneous imaging genetics data via sparse multimodal multitask learning.

机构信息

Department of Computer Science and Engineering, University of Texas at Arlington, TX 76019, USA.

出版信息

Bioinformatics. 2012 Jun 15;28(12):i127-36. doi: 10.1093/bioinformatics/bts228.

Abstract

MOTIVATION

Recent advances in brain imaging and high-throughput genotyping techniques enable new approaches to study the influence of genetic and anatomical variations on brain functions and disorders. Traditional association studies typically perform independent and pairwise analysis among neuroimaging measures, cognitive scores and disease status, and ignore the important underlying interacting relationships between these units.

RESULTS

To overcome this limitation, in this article, we propose a new sparse multimodal multitask learning method to reveal complex relationships from gene to brain to symptom. Our main contributions are three-fold: (i) introducing combined structured sparsity regularizations into multimodal multitask learning to integrate multidimensional heterogeneous imaging genetics data and identify multimodal biomarkers; (ii) utilizing a joint classification and regression learning model to identify disease-sensitive and cognition-relevant biomarkers; (iii) deriving a new efficient optimization algorithm to solve our non-smooth objective function and providing rigorous theoretical analysis on the global optimum convergency. Using the imaging genetics data from the Alzheimer's Disease Neuroimaging Initiative database, the effectiveness of the proposed method is demonstrated by clearly improved performance on predicting both cognitive scores and disease status. The identified multimodal biomarkers could predict not only disease status but also cognitive function to help elucidate the biological pathway from gene to brain structure and function, and to cognition and disease.

AVAILABILITY

Software is publicly available at: http://ranger.uta.edu/%7eheng/multimodal/.

摘要

动机

脑成像和高通量基因分型技术的最新进展,使我们能够采用新方法来研究遗传和解剖结构变异对大脑功能和疾病的影响。传统的关联研究通常在神经影像学测量、认知评分和疾病状态之间进行独立和两两分析,而忽略了这些单元之间重要的潜在相互关系。

结果

为了克服这一局限性,本文提出了一种新的稀疏多模态多任务学习方法,以揭示从基因到大脑再到症状的复杂关系。我们的主要贡献有三点:(i)将联合结构稀疏正则化引入多模态多任务学习中,以整合多维异质成像遗传学数据并识别多模态生物标志物;(ii)利用联合分类和回归学习模型识别与疾病相关且与认知相关的生物标志物;(iii)推导一种新的有效优化算法来解决我们的非光滑目标函数,并提供全局最优收敛性的严格理论分析。使用来自阿尔茨海默病神经影像学倡议数据库的成像遗传学数据,通过明显提高对认知评分和疾病状态的预测性能,验证了所提出方法的有效性。所识别的多模态生物标志物不仅可以预测疾病状态,还可以预测认知功能,有助于阐明从基因到大脑结构和功能,再到认知和疾病的生物学途径。

可用性

软件可在以下网址公开获取:http://ranger.uta.edu/~heng/multimodal/。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/489c/3371860/806760146084/bts228f1.jpg

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