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A novel framework to correct for batch effects prior to any downstream analysis in microbiome data based on Projection to Latent Structures Discriminant Analysis. The main method is named “PLSDA-batch”. It first estimates treatment and batch variation with latent components, then subtracts batch-associated components from the data whilst preserving biological variation of interest. PLSDA-batch is highly suitable for microbiome data as it is non-parametric, multivariate and allows for ordination and data visualisation. Combined with centered log-ratio transformation for addressing uneven library sizes and compositional structure, PLSDA-batch addresses all characteristics of microbiome data that existing correction methods have ignored so far. Two other variants are proposed for 1/ unbalanced batch x treatment designs that are commonly encountered in studies with small sample sizes, and for 2/ selection of discriminative variables amongst treatment groups to avoid overfitting in classification problems. These two variants have widened the scope of applicability of PLSDA-batch to different data settings.
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.
RUVnormalize is meant to remove unwanted variation from gene expression data when the factor of interest is not defined, e.g., to clean up a dataset for general use or to do any kind of unsupervised analysis.
RolDE detects longitudinal differential expression between two conditions in noisy high-troughput data. Suitable even for data with a moderate amount of missing values.RolDE is a composite method, consisting of three independent modules with different approaches to detecting longitudinal differential expression. The combination of these diverse modules allows RolDE to robustly detect varying differences in longitudinal trends and expression levels in diverse data types and experimental settings.
The HiCPotts package provides a comprehensive Bayesian framework for analyzing Hi-C interaction data, integrating both spatial and genomic biases within a probabilistic modeling framework. At its core, HiCPotts leverages the Potts model (Wu, 1982)—a well-established graphical model—to capture and quantify spatial dependencies across interaction loci arranged on a genomic lattice. By treating each interaction as a spatially correlated random variable, the Potts model enables robust segmentation of the genomic landscape into meaningful components, such as noise, true signals, and false signals. To model the influence of various genomic biases, HiCPotts employs a regression-based approach incorporating multiple covariates: Genomic distance (D): The distance between interacting loci, recognized as a fundamental driver of contact frequency. GC-content (GC): The local GC composition around the interacting loci, which can influence chromatin structure and interaction patterns. Transposable elements (TEs): The presence and abundance of repetitive elements that may shape contact probability through chromatin organization. Accessibility score (Acc): A measure of chromatin openness, informing how accessible certain genomic regions are to interaction. By embedding these covariates into a hierarchical mixture model, HiCPotts characterizes each interaction’s probability of belonging to one of several latent components. The model parameters, including regression coefficients, zero-inflation parameters (for ZIP/ZINB distributions), and dispersion terms (for NB/ZINB distributions), are inferred via a MCMC sampler. This algorithm draws samples from the joint posterior distribution, allowing for flexible posterior inference on model parameters and hidden states. From these posterior samples, HiCPotts computes posterior means of regression parameters and other quantities of interest. These posterior estimates are then used to calculate the posterior probabilities that assign each interaction to a specific component. The resulting classification sheds light on the underlying structure: distinguishing genuine high-confidence interactions (signal) from background noise and potential false signals, while simultaneously quantifying the impact of genomic biases on observed interaction frequencies. In summary, HiCPotts seamlessly integrates spatial modeling, bias correction, and probabilistic classification into a unified Bayesian inference framework. It provides rich posterior summaries and interpretable, model-based assignments of interaction states, enabling researchers to better understand the interplay between genomic organization, biases, and spatial correlation in Hi-C data.
Implementation of the adaptively weighted fisher's method, including fast p-value computing, variability index, and meta-pattern.