Dataset Information

Multimodal network diffusion predicts future disease-gene-chemical associations.

ABSTRACT: MOTIVATION:Precision medicine is an emerging field with hopes to improve patient treatment and reduce morbidity and mortality. To these ends, computational approaches have predicted associations among genes, chemicals and diseases. Such efforts, however, were often limited to using just some available association types. This lowers prediction coverage and, since prior evidence shows that integrating heterogeneous data is likely beneficial, it may limit accuracy. Therefore, we systematically tested whether using more association types improves prediction. RESULTS:We study multimodal networks linking diseases, genes and chemicals (drugs) by applying three diffusion algorithms and varying information content. Ten-fold cross-validation shows that these networks are internally consistent, both within and across association types. Also, diffusion methods recovered missing edges, even if all the edges from an entire mode of association were removed. This suggests that information is transferable between these association types. As a realistic validation, time-stamped experiments simulated the predictions of future associations based solely on information known prior to a given date. The results show that many future published results are predictable from current associations. Moreover, in most cases, using more association types increases prediction coverage without significantly decreasing sensitivity and specificity. In case studies, literature-supported validation shows that these predictions mimic human-formulated hypotheses. Overall, this study suggests that diffusion over a more comprehensive multimodal network will generate more useful hypotheses of associations among diseases, genes and chemicals, which may guide the development of precision therapies. AVAILABILITY AND IMPLEMENTATION:Code and data are available at https://github.com/LichtargeLab/multimodal-network-diffusion. SUPPLEMENTARY INFORMATION:Supplementary data are available at Bioinformatics online.

SUBMITTER: Lin CH

PROVIDER: S-EPMC6499233 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Multimodal network diffusion predicts future disease-gene-chemical associations.

Lin Chih-Hsu CH Konecki Daniel M DM Liu Meng M Wilson Stephen J SJ Nassar Huda H Wilkins Angela D AD Gleich David F DF Lichtarge Olivier O

Bioinformatics (Oxford, England) 20190501 9

<h4>Motivation</h4>Precision medicine is an emerging field with hopes to improve patient treatment and reduce morbidity and mortality. To these ends, computational approaches have predicted associations among genes, chemicals and diseases. Such efforts, however, were often limited to using just some available association types. This lowers prediction coverage and, since prior evidence shows that integrating heterogeneous data is likely beneficial, it may limit accuracy. Therefore, we systematica ...[more]

PMID: 30304494

Similar Datasets

Project description:ObjectiveTraumatic brain injury (TBI) is a heterogeneous disease with multiple neurological deficits that evolve over time. It is also associated with an increased incidence of neurodegenerative diseases. Accordingly, clinicians need better tools to predict a patient's long-term prognosis.MethodsDiffusion-weighted and anatomical MRI data were collected from 17 adolescents (mean age = 15y8mo) with moderate-to-severe TBI and 19 healthy controls. Using a network diffusion model (NDM), we examined the effect of progressive deafferentation and gray matter thinning in young TBI patients. Moreover, using a novel automated inference method, we identified several injury epicenters in order to determine the neural degenerative patterns in each TBI patient.ResultsWe were able to identify the subject-specific patterns of degeneration in each patient. In particular, the hippocampus, temporal cortices, and striatum were frequently found to be the epicenters of degeneration across the TBI patients. Orthogonal transformation of the predicted degeneration, using principal component analysis, identified distinct spatial components in the temporal-hippocampal network and the cortico-striatal network, confirming the vulnerability of these networks to injury. The NDM model, best predictive of the degeneration, was significantly correlated with time since injury, indicating that NDM can potentially capture the pathological progression in the chronic phase of TBI.InterpretationThese findings suggest that network spread may help explain patterns of distant gray matter thinning, which would be consistent with Wallerian degeneration of the white matter connections (i.e., "diaschisis") from diffuse axonal injuries and multifocal contusive injuries, and the neurodegenerative patterns of abnormal protein aggregation and transmission, which are hallmarks of brain changes in TBI. NDM approaches could provide highly subject-specific biomarkers relevant for disease monitoring and personalized therapies in TBI.

Project description:Background: Multiple modalities of Alzheimer's disease (AD) risk factors may operate through interacting networks to predict differential cognitive trajectories in asymptomatic aging. We test such a network in a series of three analytic steps. First, we test independent associations between three risk scores (functional-health, lifestyle-reserve, and a combined multimodal risk score) and cognitive [executive function (EF)] trajectories. Second, we test whether all three associations are moderated by the most penetrant AD genetic risk [Apolipoprotein E (APOE) ε4+ allele]. Third, we test whether a non-APOE AD genetic risk score further moderates these APOE × multimodal risk score associations. Methods: We assembled a longitudinal data set (spanning a 40-year band of aging, 53-95 years) with non-demented older adults (baseline n = 602; Mage = 70.63(8.70) years; 66% female) from the Victoria Longitudinal Study (VLS). The measures included for each modifiable risk score were: (1) functional-health [pulse pressure (PP), grip strength, and body mass index], (2) lifestyle-reserve (physical, social, cognitive-integrative, cognitive-novel activities, and education), and (3) the combination of functional-health and lifestyle-reserve risk scores. Two AD genetic risk markers included (1) APOE and (2) a combined AD-genetic risk score (AD-GRS) comprised of three single nucleotide polymorphisms (SNPs; Clusterin[rs11136000], Complement receptor 1[rs6656401], Phosphatidylinositol binding clathrin assembly protein[rs3851179]). The analytics included confirmatory factor analysis (CFA), longitudinal invariance testing, and latent growth curve modeling. Structural path analyses were deployed to test and compare prediction models for EF performance and change. Results: First, separate analyses showed that higher functional-health risk scores, lifestyle-reserve risk scores, and the combined score, predicted poorer EF performance and steeper decline. Second, APOE and AD-GRS moderated the association between functional-health risk score and the combined risk score, on EF performance and change. Specifically, only older adults in the APOEε4- group showed steeper EF decline with high risk scores on both functional-health and combined risk score. Both associations were further magnified for adults with high AD-GRS. Conclusion: The present multimodal AD risk network approach incorporated both modifiable and genetic risk scores to predict EF trajectories. The results add an additional degree of precision to risk profile calculations for asymptomatic aging populations.

Dataset Information

Multimodal network diffusion predicts future disease-gene-chemical associations.

Publications

Multimodal network diffusion predicts future disease-gene-chemical associations.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets