{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:15:31Z","timestamp":1777396531814,"version":"3.51.4"},"reference-count":63,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2024,5,14]]},"abstract":"<jats:p>Background: There are various molecular hypotheses regarding Alzheimer\u2019s disease (AD) like amyloid deposition, tau propagation, neuroinflammation, and synaptic dysfunction. However, detailed molecular mechanism underlying AD remains elusive. In addition, genetic contribution of these molecular hypothesis is not yet established despite the high heritability of AD. Objective: The study aims to enable the discovery of functionally connected multi-omic features through novel integration of multi-omic data and prior functional interactions. Methods: We propose a new deep learning model MoFNet with improved interpretability to investigate the AD molecular mechanism and its upstream genetic contributors. MoFNet integrates multi-omic data with prior functional interactions between SNPs, genes, and proteins, and for the first time models the dynamic information flow from DNA to RNA and proteins. Results: When evaluated using the ROS\/MAP cohort, MoFNet outperformed other competing methods in prediction performance. It identified SNPs, genes, and proteins with significantly more prior functional interactions, resulting in three multi-omic subnetworks. SNP-gene pairs identified by MoFNet were mostly eQTLs specific to frontal cortex tissue where gene\/protein data was collected. These molecular subnetworks are enriched in innate immune system, clearance of misfolded proteins, and neurotransmitter release respectively. We validated most findings in an independent dataset. One multi-omic subnetwork consists exclusively of core members of SNARE complex, a key mediator of synaptic vesicle fusion and neurotransmitter transportation. Conclusions: Our results suggest that MoFNet is effective in improving classification accuracy and in identifying multi-omic markers for AD with improved interpretability. Multi-omic subnetworks identified by MoFNet provided insights of AD molecular mechanism with improved details.<\/jats:p>","DOI":"10.3233\/jad-240098","type":"journal-article","created":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T11:39:59Z","timestamp":1715341199000},"page":"715-727","source":"Crossref","is-referenced-by-count":2,"title":["Deep Trans-Omic Network Fusion for Molecular Mechanism of Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"99","author":[{"given":"Linhui","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Electrical and Computer Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN, USA"},{"name":"Indiana Alzheimer\u2019s Disease Research Center, Indianapolis, IN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yash","family":"Raj","sequence":"additional","affiliation":[{"name":"Department of BioHealth Informatics, Indiana University Purdue University Indianapolis, Indianapolis, IN, 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Methodol"},{"key":"10.3233\/JAD-240098_ref20","doi-asserted-by":"crossref","first-page":"3991","DOI":"10.1093\/bioinformatics\/btv497","article-title":"glmgraph: An R package for variable selection and predictive modeling of structured genomic data","volume":"31","author":"Chen","year":"2015","journal-title":"Bioinformatics"},{"key":"10.3233\/JAD-240098_ref21","first-page":"2825","article-title":"Scikit-learn: Machine learning in Python","volume":"12","author":"Pedregosa","year":"2011","journal-title":"J Mach Learn Res"},{"key":"10.3233\/JAD-240098_ref22","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nrneurol.2012.263","article-title":"Apolipoprotein E and Alzheimer disease: Risk, mechanisms and therapy","volume":"9","author":"Liu","year":"2013","journal-title":"Nat Rev Neurol"},{"key":"10.3233\/JAD-240098_ref23","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/0304-3940(95)11484-E","article-title":"Monoclonal antibody AT8 recognises tau protein phosphorylated at both serine 202 and threonine 205","volume":"189","author":"Goedert","year":"1995","journal-title":"Neurosci Lett"},{"key":"10.3233\/JAD-240098_ref24","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1046\/j.1432-1327.1998.2520542.x","article-title":"Sequential phosphorylation of Tau by glycogen synthase kinase-3beta and protein kinase A at Thr212 and Ser214 generates the Alzheimer-specific epitope of antibody AT100 and requires a paired-helical-filament-like conformation","volume":"252","author":"Zheng-Fischhofer","year":"1998","journal-title":"Eur J Biochem"},{"key":"10.3233\/JAD-240098_ref25","doi-asserted-by":"crossref","first-page":"2922","DOI":"10.1016\/j.febslet.2006.02.067","article-title":"Tau phosphorylation and aggregation in Alzheimer\u2019s disease pathology","volume":"580","author":"Avila","year":"2006","journal-title":"FEBS 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