Search arXivSearch

arXiv · 1101.1377

A Bayesian graphical modeling approach to microRNA regulatory network inference

Abstract

It has been estimated that about 30% of the genes in the human genome are regulated by microRNAs (miRNAs). These are short RNA sequences that can down-regulate the levels of mRNAs or proteins in animals and plants. Genes regulated by miRNAs are called targets. Typically, methods for target prediction are based solely on sequence data and on the structure information. In this paper we propose a Bayesian graphical modeling approach that infers the miRNA regulatory network by integrating expression levels of miRNAs with their potential mRNA targets and, via the prior probability model, with their sequence/structure information. We use a directed graphical model with a particular structure adapted to our data based on biological considerations. We then achieve network inference using stochastic search methods for variable selection that allow us to explore the huge model space via MCMC. A time-dependent coefficients model is also implemented. We consider experimental data from a study on a very well-known developmental toxicant causing neural tube defects, hyperthermia. Some of the pairs of target gene and miRNA we identify seem very plausible and warrant future investigation. Our proposed method is general and can be easily applied to other types of network inference by integrating multiple data sources.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Francesco C. Stingo, Yian A. Chen, Marina Vannucci, Marianne Barrier, Philip E. Mirkes. 2011-01-07. A Bayesian graphical modeling approach to microRNA regulatory network inference. https://doi.org/10.1214/10-aoas360

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

Geospatial Foundation Models Capture Health-Relevant Dimensions of Place Beyond Conventional Social Risk Indices

Area-based social risk indices summarize residents' socioeconomic conditions but incompletely capture physical features of place that may affect health. We evaluated whether numerical representations of physical place produced by four geospatial foundation model families from 2022 satellite data explained residual variance in tract-level associations between the Area Deprivation Index, Social Deprivation Index, and Social Vulnerability Index with health outcomes. We used LightGBM to predict variables from the American Community Survey and 40 chronic disease and health-behavior outcomes from CDC PLACES across 82,646 census tracts in the contiguous United States, evaluating performance across 10 held-out states. Among survey variables, models were moderately predictive of some variables including housing type (R-squared up to 0.54) but weak for disability, unemployment, and income disparity. For health outcomes, models explained up to 54% of variance left unexplained by social risk indices, with the largest gains for annual checkups, arthritis, and high blood pressure. Mean total variance explained by geospatial foundation models across the 40 health-related outcomes increased from 0.31 in the smallest tract-size decile to 0.39 in the largest. Geospatial foundation models capture health-relevant features of place not represented by conventional social risk indices and may usefully augment them in epidemiological analyses.

stat.AP

Transporting summary measures of relative effects from randomised trials to the treated patient population: an application to breast cancer endocrine therapy

Randomised trials often report relative treatment effects, such as risk ratios and hazard ratios, for trial populations. Clinical decision-making, however, often benefits from estimates of absolute treatment effects in the population eligible for treatment. Trial participants may not represent this target population well, and restrictions on access to individual participant trial data can further complicate absolute effect estimation. Routine care data are often representative of the target population but may be subject to uncontrolled confounding. We consider estimation of the average treatment effect on the treated (ATT), an absolute measure, by combining a representative sample of treated routine care patients with summary measures (i.e., estimated risk or hazard ratios) from either a randomised trial or a meta-analysis of trials. Under marginal or conditional transportability assumptions, the ATT is shown to be identifiable. The implications of collapsibility of the effect measure on transportability are discussed, and plug-in estimators of the ATT are presented. Simulation studies are used to assess finite sample performance of the estimators in a range of settings. The proposed methods are applied to estimate the ATT of endocrine therapy on 15-year breast cancer mortality using results from a meta-analysis of randomised trials and England's National Disease Registration Service.

stat.AP

Overcoming Model Misspecification in Bayesian Inference of Molecular Signalling Networks

Bayesian inference of molecular signalling networks usually relies on tractability of the marginal likelihood, enabling the set of possible networks to be efficiently explored. As such, linear models with independent errors and conjugate priors are routinely used. However, the dynamics of molecular signalling are nonlinear, and relevant confounders are often unobserved; failure to account for these complexities will almost certainly lead to over-confident inferences in the standard Bayesian framework. To confront this reality, we develop a post-Bayesian approach to inference of molecular signalling networks, guided by the principle that uncertainty should not vanish when the statistical model is misspecified, even in the infinite-data limit. Technically, we extend the predictively-oriented (PrO) posterior of McLatchie et al. (2025) to the setting of latent variable models, empirically investigating the properties of PrO posteriors in the challenging network inference context.

stat.AP