nucleoSim

An elaborate molecular evolutionary framework that facilitates straightforward simulation of codon genetic sequences subjected to different degrees and/or patterns of Darwinian selection. The model is built upon the fitness landscape paradigm of Sewall Wright, as popularised by the mutation-selection model of Halpern and Bruno. This enables realistic evolutionary process of living organisms to be reproducible seamlessly. For example, an Ornstein-Uhlenbeck fitness update algorithm is incorporated herein. Consequently, otherwise complex biological processes, such as the effect of the interplay between genetic drift and fitness landscape fluctuations on the inference of diversifying selection, may now be investigated with minimal effort. Frequency-dependent and stochastic fitness landscape update techniques are available.

Biological inferences obtained from molecular data are only as good as the extent of evolutionary signatures retained in the genetic data. Techniques available to quantify these signatures are largely targeted towards phylogeny reconstruction and they often rely on adhoc hypothesis tests of significance. I present a Bayesian function that assesses whether a set of genetic sequences are saturated. That is, it is useful for determining whether the evolutionary information in the sequences has eroded with time. Site specific Bayes factors are generated with respect to codon bases to allow for straightforward applications in extensive computational biology inquiries, including natural selection analyses.

BANDITS is a Bayesian hierarchical model for detecting differential splicing of genes and transcripts, via differential transcript usage (DTU), between two or more conditions. The method uses a Bayesian hierarchical framework, which allows for sample specific proportions in a Dirichlet-Multinomial model, and samples the allocation of fragments to the transcripts. Parameters are inferred via Markov chain Monte Carlo (MCMC) techniques and a DTU test is performed via a multivariate Wald test on the posterior densities for the average relative abundance of transcripts.

IsoBayes is a Bayesian method to perform inference on single protein isoforms. Our approach infers the presence/absence of protein isoforms, and also estimates their abundance; additionally, it provides a measure of the uncertainty of these estimates, via: i) the posterior probability that a protein isoform is present in the sample; ii) a posterior credible interval of its abundance. IsoBayes inputs liquid cromatography mass spectrometry (MS) data, and can work with both PSM counts, and intensities. When available, trascript isoform abundances (i.e., TPMs) are also incorporated: TPMs are used to formulate an informative prior for the respective protein isoform relative abundance. We further identify isoforms where the relative abundance of proteins and transcripts significantly differ. We use a two-layer latent variable approach to model two sources of uncertainty typical of MS data: i) peptides may be erroneously detected (even when absent); ii) many peptides are compatible with multiple protein isoforms. In the first layer, we sample the presence/absence of each peptide based on its estimated probability of being mistakenly detected, also known as PEP (i.e., posterior error probability). In the second layer, for peptides that were estimated as being present, we allocate their abundance across the protein isoforms they map to. These two steps allow us to recover the presence and abundance of each protein isoform.

Characterization of intra-individual variability using physiologically relevant measurements provides important insights into fundamental biological questions ranging from cell type identity to tumor development. For each individual, the data measurements can be written as a matrix with the different subsamples of the individual recorded in the columns and the different phenotypic units recorded in the rows. Datasets of this type are called high-dimensional transposable data. The HDTD package provides functions for conducting statistical inference for the mean relationship between the row and column variables and for the covariance structure within and between the row and column variables.

A collection of methods for performing random rotations on high-dimensional, normally distributed data (e.g. microarray or RNA-seq data) with batch structure. The random rotation approach allows exact testing of dependent test statistics with linear models following arbitrary batch effect correction methods.