Polee: RNA-Seq analysis using approximate likelihood

The analysis of mRNA transcript abundance with RNA-Seq is a central tool in molecular biology research, but often analyses fail to account for the uncertainty in these estimates, which can be significant, especially when trying to disentangle isoforms or duplicated genes. Preserving uncertainty necessitates a full probabilistic model of the all the sequencing reads, which quickly becomes intractable, as experiments can consist of billions of reads. To overcome these limitations, we propose a new method of approximating the likelihood function of a sparse mixture model, using a technique we call the Pólya tree transformation. We demonstrate that substituting this approximation for the real thing achieves most of the benefits with a fraction of the computational costs, leading to more accurate detection of differential transcript expression and transcript coexpression.

Estimation of Receiver Operating Characteristic Surface Using Mixtures of Finite Polya Trees (MFPT)

Generalisation of Receiver operating characteristic (ROC) curve has become increasingly useful in evaluating the performance of diagnostic tests that have more than binary outcomes. While parametric approaches have been widely used over the years, the limitations associated with parametric assumptions often make it difficult to modelling the volume under surface for data that do not meet criteria under parametric distributions. As such, estimation of ROC surface using nonparametric approaches have been proposed to obtained insights on available data. One of the common approaches to non-parametric estimation is the use of Bayesian models where assumptions about priors can be made then posterior distributions obtained which can then be used to model the data. This study uses Polya tree priors where mixtures of Polya trees approach was used to model simulated three-way ROC data. The results of VUS estimation which is considered a suitable inference in evaluating performance of a diagnostic test, indicated that the mixtures of Polya trees model fitted well the ROC surface data. Further, the model performed relatively well compared to parametric and semiparametric models under similar assumptions.  

Polee: RNA-Seq analysis using approximate likelihood

The analysis of mRNA transcript abundance with RNA-Seq is a central tool in molecular biology research, but often analyses fail to account for the uncertainty in these estimates, which can be significant, especially when trying to disentangle isoforms or duplicated genes. Preserving un-certainty necessitates a full probabilistic model of the all the sequencing reads, which quickly becomes intractable, as experiments can consist of billions of reads. To overcome these limitations, we propose a new method of approximating the likelihood function of a sparse mixture model, using a technique we call the Pólya tree transformation. We demonstrate that substituting this approximation for the real thing achieves most of the benefits with a fraction of the computational costs, leading to more accurate detection of differential transcript expression.AvailabilityThe method is implemented in a Julia package available from https://github.com/dcjones/[email protected]