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1. Multi-Task Sparse Canonical Correlation Analysis with Application to Multi-Modal Brain Imaging Genetics

   https://doi.org/10.1109/TCBB.2019.2947428  

   Du, Lei ; Liu, Kefei ; Yao, Xiaohui ; Risacher, Shannon ; Han, Junwei ; Saykin, Andrew ; Guo, Lei ; Shen, Li ( October 2019 , IEEE/ACM Transactions on Computational Biology and Bioinformatics)

   Brain imaging genetics studies the genetic basis of brain structures and functionalities via integrating genotypic data such as single nucleotide polymorphisms (SNPs) and imaging quantitative traits (QTs). In this area, both multi-task learning (MTL) and sparse canonical correlation analysis (SCCA) methods are widely used since they are superior to those independent and pairwise univariate analysis. MTL methods generally incorporate a few of QTs and could not select features from multiple QTs; while SCCA methods typically employ one modality of QTs to study its association with SNPs. Both MTL and SCCA are computational expensive as the number of SNPs increases. Inmore »this paper, we propose a novel multi-task SCCA (MTSCCA) method to identify bi-multivariate associations between SNPs and multi-modal imaging QTs. MTSCCA could make use of the complementary information carried by different imaging modalities. MTSCCA enforces sparsity at the group level via the G2,1-norm, and jointly selects features across multiple tasks for SNPs and QTs via the L2,1-norm. A fast optimization algorithm is proposed using the grouping information of SNPs. Compared with conventional SCCA methods, MTSCCA obtains better correlation coefficients and canonical weights patterns. In addition, MTSCCA runs very fast and easy-to-implement, indicating its potential power in genome-wide brain-wide imaging genetics.« less
2. Mining Regional Imaging Genetic Associations via Voxel-wise Enrichment Analysis

   https://doi.org/10.1109/BHI.2019.8834450  

   Yao, Xiaohui ; Cong, Shan ; Yan, Jingwen ; Risacher, Shannon L. ; Saykin, Andrew J. ; Moore, Jason H. ; Shen, Li ( May 2019 , 2019 IEEE EMBS International Conference on Biomedical & Health Informatics (BHI))

   Brain imaging genetics aims to reveal genetic effects on brain phenotypes, where most studies examine phenotypes defined on anatomical or functional regions of interest (ROIs) given their biologically meaningful annotation and modest dimensionality compared with voxel-wise approaches. Typical ROI-level measures used in these studies are summary statistics from voxel-wise measures in the region, without making full use of individual voxel signals. In this paper, we propose a flexible and powerful framework for mining regional imaging genetic associations via voxel-wise enrichment analysis, which embraces the collective effect of weak voxel-level signals within an ROI. We demonstrate our method on an imagingmore »genetic analysis using data from the Alzheimers Disease Neuroimaging Initiative, where we assess the collective regional genetic effects of voxel-wise FDG-PET measures between 116 ROIs and 19 AD candidate SNPs. Compared with traditional ROI-wise and voxel-wise approaches, our method identified 102 additional significant associations, some of which were further supported by evidences in brain tissue-specific expression analysis. This demonstrates the promise of the proposed method as a flexible and powerful framework for exploring imaging genetic effects on the brain.« less
3. Integrative analysis of eQTL and GWAS summary statistics reveals transcriptomic alteration in Alzheimer brains

   https://doi.org/10.1186/s12920-022-01245-5  

   Varathan, Pradeep ; Gorijala, Priyanka ; Jacobson, Tanner ; Chasioti, Danai ; Nho, Kwangsik ; Risacher, Shannon L. ; Saykin, Andrew J. ; Yan, Jingwen ( December 2022 , BMC Medical Genomics)

   Abstract Background Large-scale genome-wide association studies have successfully identified many genetic variants significantly associated with Alzheimer’s disease (AD), such as rs429358, rs11038106, rs723804, rs13591776, and more. The next key step is to understand the function of these SNPs and the downstream biology through which they exert the effect on the development of AD. However, this remains a challenging task due to the tissue-specific nature of transcriptomic and proteomic data and the limited availability of brain tissue.In this paper, instead of using coupled transcriptomic data, we performed an integrative analysis of existing GWAS findings and expression quantitative trait loci (eQTL) resultsmore »from AD-related brain regions to estimate the transcriptomic alterations in AD brain. Results We used summary-based mendelian randomization method along with heterogeneity in dependent instruments method and were able to identify 32 genes with potential altered levels in temporal cortex region. Among these, 10 of them were further validated using real gene expression data collected from temporal cortex region, and 19 SNPs from NECTIN and TOMM40 genes were found associated with multiple temporal cortex imaging phenotype. Conclusion Significant pathways from enriched gene networks included neutrophil degranulation, Cell surface interactions at the vascular wall, and Regulation of TP53 activity which are still relatively under explored in Alzheimer’s Disease while also encouraging a necessity to bind further trans-eQTL effects into this integrative analysis.« less
4. Multi-task Multimodal Learning for Disaster Situation Assessment

   https://doi.org/10.1109/MIPR49039.2020.00050  

   Wang, Tianyi ; Tao, Yudong ; Chen, Shu-Ching ; Shyu, Mei-Ling ( August 2020 , 2020 IEEE Conference on Multimedia Information Processing and Retrieval (MIPR))

   During disaster events, emergency response teams need to draw up the response plan at the earliest possible stage. Social media platforms contain rich information which could help to assess the current situation. In this paper, a novel multi-task multimodal deep learning framework with automatic loss weighting is proposed. Our framework is able to capture the correlation among different concepts and data modalities. The proposed automatic loss weighting method can prevent the tedious manual weight tuning process and improve the model performance. Extensive experiments on a large-scale multimodal disaster dataset from Twitter are conducted to identify post-disaster humanitarian category and infrastructuremore »damage level. The results show that by learning the shared latent space of multiple tasks with loss weighting, our model can outperform all single tasks.« less
5. Bridging Imaging, Genetics, and Diagnosis in a Coupled Low-Dimensional Framework

   Sayan Ghosal, Qiang Chen ( October 2019 , Medical Image Computing and Computer Assisted Intervention)

   We propose a joint dictionary learning framework that couples imaging and genetics data in a low dimensional subspace as guided by clinical diagnosis. We use a graph regularization penalty to simultaneously capture inter-regional brain interactions and identify the representative set anatomical basis vectors that span the low dimensional space. We further employ group sparsity to find the representative set of genetic basis vectors that span the same latent space. Finally, the latent projection is used to classify patients versus controls. We have evaluated our model on two task fMRI paradigms and single nucleotide polymorphism (SNP) data from schizophrenic patients andmore »matched neurotypical controls. We employ a ten fold cross validation technique to show the predictive power of our model. We compare our model with canonical correlation analysis of imaging and genetics data and random forest classification. Our approach shows better prediction accuracy on both task datasets. Moreover, the implicated brain regions and genetic variants underlie the well documented deficits in schizophrenia.« less