ArticleJournal of the American Medical Informatics Association : JAMIA
Translating Mendelian and complex inheritance of Alzheimer's disease genes for predicting unique personal genome variants.
Article in Journal of the American Medical Informatics Association : JAMIA. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.
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Who cites it
14 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Macroscale Gradient Dysfunction in Alzheimer's Disease: Patterns With Cognition Terms and Gene Expression Profiles.Human brain mapping · 2024Pooled it
- Dissecting Complex and Multifactorial Nature of Alzheimer's Disease Pathogenesis: a Clinical, Genomic, and Systems Biology Perspective.Molecular neurobiology · 2016Pooled it
- A phenome-wide association study of 26 mendelian genes reveals phenotypic expressivity of common and rare variants within the general population.PLoS genetics · 2020Article
- Convergent downstream candidate mechanisms of independent intergenic polymorphisms between co-classified diseases implicate epistasis among noncoding elements.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2018Article
- kMEn: Analyzing noisy and bidirectional transcriptional pathway responses in single subjects.Journal of biomedical informatics · 2017Article
- eQTL networks unveil enriched mRNA master integrators downstream of complex disease-associated SNPs.Journal of biomedical informatics · 2015Article
- Dynamic changes of RNA-sequencing expression for precision medicine: N-of-1-pathways Mahalanobis distance within pathways of single subjects predicts breast cancer survival.Bioinformatics (Oxford, England) · 2015Article
- Towards a PBMC "virogram assay" for precision medicine: Concordance between ex vivo and in vivo viral infection transcriptomes.Journal of biomedical informatics · 2015Article
- Adapting simultaneous analysis phylogenomic techniques to study complex disease gene relationships.Journal of biomedical informatics · 2015Article
- Genomic convergence and network analysis approach to identify candidate genes in Alzheimer's disease.BMC genomics · 2014Article
- COPD Hospitalization Risk Increased with Distinct Patterns of Multiple Systems Comorbidities Unveiled by Network Modeling.AMIA ... Annual Symposium proceedings. AMIA Symposium · 2014Article
- Concordance of deregulated mechanisms unveiled in underpowered experiments: PTBP1 knockdown case study.BMC medical genomics · 2014Article
- Recent trends in biomedical informatics: a study based on JAMIA articles.Journal of the American Medical Informatics Association : JAMIA · 2013Article
- Integrative genomics analyses unveil downstream biological effectors of disease-specific polymorphisms buried in intergenic regions.NPJ genomic medicineArticle
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Authors and funding
8 authors.
Funding
Abstract
objectiveAlthough trait-associated genes identified as complex versus single-gene inheritance differ substantially in odds ratio, the authors nonetheless posit that their mechanistic concordance can reveal fundamental properties of the genetic architecture, allowing the automated interpretation of unique polymorphisms within a personal genome. MATERIALS AND
methodsAn analytical method, SPADE-gen, spanning three biological scales was developed to demonstrate the mechanistic concordance between Mendelian and complex inheritance of Alzheimer's disease (AD) genes: biological functions (BP), protein interaction modeling, and protein domain implicated in the disease-associated polymorphism.
resultsAmong Gene Ontology (GO) biological processes (BP) enriched at a false detection rate <5% in 15 AD genes of Mendelian inheritance (Online Mendelian Inheritance in Man) and independently in those of complex inheritance (25 host genes of intragenic AD single-nucleotide polymorphisms confirmed in genome-wide association studies), 16 overlapped (empirical p=0.007) and 45 were similar (empirical p<0.009; information theory). SPAN network modeling extended the canonical pathway of AD (KEGG) with 26 new protein interactions (empirical p<0.0001). DISCUSSION: The study prioritized new AD-associated biological mechanisms and focused the analysis on previously unreported interactions associated with the biological processes of polymorphisms that affect specific protein domains within characterized AD genes and their direct interactors using (1) concordant GO-BP and (2) domain interactions within STRING protein-protein interactions corresponding to the genomic location of the AD polymorphism (eg, EPHA1, APOE, and CD2AP).
conclusionThese results are in line with unique-event polymorphism theory, indicating how disease-associated polymorphisms of Mendelian or complex inheritance relate genetically to those observed as 'unique personal variants'. They also provide insight for identifying novel targets, for repositioning drugs, and for personal therapeutics.
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