Oscope

Distance-correlation based Gene Set Analysis for longitudinal gene expression profiles. In longitudinal studies, the gene expression profiles were collected at each visit from each subject and hence there are multiple measurements of the gene expression profiles for each subject. The dcGSA package could be used to assess the associations between gene sets and clinical outcomes of interest by fully taking advantage of the longitudinal nature of both the gene expression profiles and clinical outcomes.

Estimate variance-mean dependence in count data from high-throughput sequencing assays and test for differential expression based on a model using the negative binomial distribution.

A differential abundance analysis for the comparison of two or more conditions. Useful for analyzing data from standard RNA-seq or meta-RNA-seq assays as well as selected and unselected values from in-vitro sequence selections. Uses a Dirichlet-multinomial model to infer abundance from counts, optimized for three or more experimental replicates. The method infers biological and sampling variation to calculate the expected false discovery rate, given the variation, based on a Wilcoxon Rank Sum test and Welch's t-test (via aldex.ttest), a Kruskal-Wallis test (via aldex.kw), a generalized linear model (via aldex.glm), or a correlation test (via aldex.corr). All tests report predicted p-values and posterior Benjamini-Hochberg corrected p-values. ALDEx2 also calculates expected standardized effect sizes for paired or unpaired study designs. ALDEx2 can now be used to estimate the effect of scale on the results and report on the scale-dependent robustness of results.

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.

The package generally provides methods for gene set enrichment analysis of high-throughput RNA-Seq data by integrating differential expression and splicing. It uses negative binomial distribution to model read count data, which accounts for sequencing biases and biological variation. Based on permutation tests, statistical significance can also be achieved regarding each gene's differential expression and splicing, respectively.

The sva package contains functions for removing batch effects and other unwanted variation in high-throughput experiment. Specifically, the sva package contains functions for the identifying and building surrogate variables for high-dimensional data sets. Surrogate variables are covariates constructed directly from high-dimensional data (like gene expression/RNA sequencing/methylation/brain imaging data) that can be used in subsequent analyses to adjust for unknown, unmodeled, or latent sources of noise. The sva package can be used to remove artifacts in three ways: (1) identifying and estimating surrogate variables for unknown sources of variation in high-throughput experiments (Leek and Storey 2007 PLoS Genetics,2008 PNAS), (2) directly removing known batch effects using ComBat (Johnson et al. 2007 Biostatistics) and (3) removing batch effects with known control probes (Leek 2014 biorXiv). Removing batch effects and using surrogate variables in differential expression analysis have been shown to reduce dependence, stabilize error rate estimates, and improve reproducibility, see (Leek and Storey 2007 PLoS Genetics, 2008 PNAS or Leek et al. 2011 Nat. Reviews Genetics).