TY - JOUR
T1 - inMTSCCA
T2 - An Integrated Multi-task Sparse Canonical Correlation Analysis for Multi-omic Brain Imaging Genetics
AU - the Alzheimer's Disease Neuroimaging Initiative
AU - Du, Lei
AU - Zhang, Jin
AU - Zhao, Ying
AU - Shang, Muheng
AU - Guo, Lei
AU - Han, Junwei
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/4
Y1 - 2023/4
N2 - Identifying genetic risk factors for Alzheimer's disease (AD) is an important research topic. To date, different endophenotypes, such as imaging-derived endophenotypes and proteomic expression-derived endophenotypes, have shown the great value in uncovering risk genes compared to case–control studies. Biologically, a co-varying pattern of different omics-derived endophenotypes could result from the shared genetic basis. However, existing methods mainly focus on the effect of endophenotypes alone; the effect of cross-endophenotype (CEP) associations remains largely unexploited. In this study, we used both endophenotypes and their CEP associations of multi-omic data to identify genetic risk factors, and proposed two integrated multi-task sparse canonical correlation analysis (inMTSCCA) methods, i.e., pairwise endophenotype correlation-guided MTSCCA (pcMTSCCA) and high-order endophenotype correlation-guided MTSCCA (hocMTSCCA). pcMTSCCA employed pairwise correlations between magnetic resonance imaging (MRI)-derived, plasma-derived, and cerebrospinal fluid (CSF)-derived endophenotypes as an additional penalty. hocMTSCCA used high-order correlations among these multi-omic data for regularization. To figure out genetic risk factors at individual and group levels, as well as altered endophenotypic markers, we introduced sparsity-inducing penalties for both models. We compared pcMTSCCA and hocMTSCCA with three related methods on both simulation and real (consisting of neuroimaging data, proteomic analytes, and genetic data) datasets. The results showed that our methods obtained better or comparable canonical correlation coefficients (CCCs) and better feature subsets than benchmarks. Most importantly, the identified genetic loci and heterogeneous endophenotypic markers showed high relevance. Therefore, jointly using multi-omic endophenotypes and their CEP associations is promising to reveal genetic risk factors. The source code and manual of inMTSCCA are available at https://ngdc.cncb.ac.cn/biocode/tools/BT007330.
AB - Identifying genetic risk factors for Alzheimer's disease (AD) is an important research topic. To date, different endophenotypes, such as imaging-derived endophenotypes and proteomic expression-derived endophenotypes, have shown the great value in uncovering risk genes compared to case–control studies. Biologically, a co-varying pattern of different omics-derived endophenotypes could result from the shared genetic basis. However, existing methods mainly focus on the effect of endophenotypes alone; the effect of cross-endophenotype (CEP) associations remains largely unexploited. In this study, we used both endophenotypes and their CEP associations of multi-omic data to identify genetic risk factors, and proposed two integrated multi-task sparse canonical correlation analysis (inMTSCCA) methods, i.e., pairwise endophenotype correlation-guided MTSCCA (pcMTSCCA) and high-order endophenotype correlation-guided MTSCCA (hocMTSCCA). pcMTSCCA employed pairwise correlations between magnetic resonance imaging (MRI)-derived, plasma-derived, and cerebrospinal fluid (CSF)-derived endophenotypes as an additional penalty. hocMTSCCA used high-order correlations among these multi-omic data for regularization. To figure out genetic risk factors at individual and group levels, as well as altered endophenotypic markers, we introduced sparsity-inducing penalties for both models. We compared pcMTSCCA and hocMTSCCA with three related methods on both simulation and real (consisting of neuroimaging data, proteomic analytes, and genetic data) datasets. The results showed that our methods obtained better or comparable canonical correlation coefficients (CCCs) and better feature subsets than benchmarks. Most importantly, the identified genetic loci and heterogeneous endophenotypic markers showed high relevance. Therefore, jointly using multi-omic endophenotypes and their CEP associations is promising to reveal genetic risk factors. The source code and manual of inMTSCCA are available at https://ngdc.cncb.ac.cn/biocode/tools/BT007330.
KW - Brain imaging genetics
KW - Cross-endophenotype association
KW - Genetic risk factor
KW - Medical image analysis
KW - Multi-omic endophenotype
UR - http://www.scopus.com/inward/record.url?scp=85168756838&partnerID=8YFLogxK
U2 - 10.1016/j.gpb.2023.03.005
DO - 10.1016/j.gpb.2023.03.005
M3 - 文章
C2 - 37442417
AN - SCOPUS:85168756838
SN - 1672-0229
VL - 21
SP - 396
EP - 413
JO - Genomics, Proteomics and Bioinformatics
JF - Genomics, Proteomics and Bioinformatics
IS - 2
ER -