ArticleJournal of the American Medical Informatics Association : JAMIA
Complex-disease networks of trait-associated single-nucleotide polymorphisms (SNPs) unveiled by information theory.
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 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed.
- Distributed transformer for high order epistasis detection in large-scale datasets.Scientific reports · 2024Article
- Phenome-wide association network demonstrates close connection with individual disease trajectories from the HUNT study.PloS one · 2024Article
- Epithelial cell responses to rhinovirus identify an early-life-onset asthma phenotype in adults.The Journal of allergy and clinical immunology · 2022Article
- Novel disease syndromes unveiled by integrative multiscale network analysis of diseases sharing molecular effectors and comorbidities.BMC medical genomics · 2018Article
- A Network-Biology Informed Computational Drug Repositioning Strategy to Target Disease Risk Trajectories and Comorbidities of Peripheral Artery Disease.AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science · 2018Article
- 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
- Evidence of selection on splicing-associated loci in human populations and relevance to disease loci mapping.Scientific reports · 2017Article
- A disease similarity matrix based on the uniqueness of shared genes.BMC medical genomics · 2017Article
- kMEn: Analyzing noisy and bidirectional transcriptional pathway responses in single subjects.Journal of biomedical informatics · 2017Article
- A new approach to disentangle genetic and epigenetic components on disease comorbidities: studying correlation between genotypic and phenotypic disease networks.Procedia computer science · 2017Article
- Biomechanisms of Comorbidity: Reviewing Integrative Analyses of Multi-omics Datasets and Electronic Health Records.Yearbook of medical informatics · 2016Review
- AN INTEGRATED NETWORK APPROACH TO IDENTIFYING BIOLOGICAL PATHWAYS AND ENVIRONMENTAL EXPOSURE INTERACTIONS IN COMPLEX DISEASES.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2016Article
- 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
- Comparative analysis of a novel disease phenotype network based on clinical manifestations.Journal of biomedical informatics · 2015Article
- Network-based prediction and knowledge mining of disease genes.BMC medical genomics · 2015Article
- Genome-wide genetic interaction analysis of glaucoma using expert knowledge derived from human phenotype networks.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2015Article
- Disease risk factors identified through shared genetic architecture and electronic medical records.Science translational medicine · 2014Article
- The multiscale backbone of the human phenotype network based on biological pathways.BioData mining · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
objectiveThousands of complex-disease single-nucleotide polymorphisms (SNPs) have been discovered in genome-wide association studies (GWAS). However, these intragenic SNPs have not been collectively mined to unveil the genetic architecture between complex clinical traits. The authors hypothesize that biological annotations of host genes of trait-associated SNPs may reveal the biomolecular modularity across complex-disease traits and offer insights for drug repositioning.
methodsTrait-to-polymorphism (SNPs) associations confirmed in GWAS were used. A novel method to quantify trait-trait similarity anchored in Gene Ontology annotations of human proteins and information theory was developed. The results were then validated with the shortest paths of physical protein interactions between biologically similar traits.
resultsA network was constructed consisting of 280 significant intertrait similarities among 177 disease traits, which covered 1438 well-validated disease-associated SNPs. Thirty-nine percent of intertrait connections were confirmed by curators, and the following additional studies demonstrated the validity of a proportion of the remainder. On a phenotypic trait level, higher Gene Ontology similarity between proteins correlated with smaller 'shortest distance' in protein interaction networks of complexly inherited diseases (Spearman p<2.2×10(-16)). Further, 'cancer traits' were similar to one another, as were 'metabolic syndrome traits' (Fisher's exact test p=0.001 and 3.5×10(-7), respectively).
conclusionAn imputed disease network by information-anchored functional similarity from GWAS trait-associated SNPs is reported. It is also demonstrated that small shortest paths of protein interactions correlate with complex-disease function. Taken together, these findings provide the framework for investigating drug targets with unbiased functional biomolecular networks rather than worn-out single-gene and subjective canonical pathway approaches.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.