spaSim

A novel approach utilizing a homogeneous hidden Markov model. And effectively model untransformed beta values. To identify DMCs while considering the spatial. Correlation of the adjacent CpG sites.

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.

Intuitive framework for identifying spatially variable genes (SVGs) and differential spatial variable pattern (DSP) between conditions via edgeR, a popular method for performing differential expression analyses. Based on pre-annotated spatial clusters as summarized spatial information, DESpace models gene expression using a negative binomial (NB), via edgeR, with spatial clusters as covariates. SVGs are then identified by testing the significance of spatial clusters. For multi-sample, multi-condition datasets, we again fit a NB model via edgeR, incorporating spatial clusters, conditions and their interactions as covariates. DSP genes-representing differences in spatial gene expression patterns across experimental conditions-are identified by testing the interaction between spatial clusters and conditions.

The goal of `tpSVG` is to detect and visualize spatial variation in the gene expression for spatially resolved transcriptomics data analysis. Specifically, `tpSVG` introduces a family of count-based models, with generalizable parametric assumptions such as Poisson distribution or negative binomial distribution. In addition, comparing to currently available count-based model for spatially resolved data analysis, the `tpSVG` models improves computational time, and hence greatly improves the applicability of count-based models in SRT data analysis.

`SPOTlight` provides a method to deconvolute spatial transcriptomics spots using a seeded NMF approach along with visualization tools to assess the results. Spatially resolved gene expression profiles are key to understand tissue organization and function. However, novel spatial transcriptomics (ST) profiling techniques lack single-cell resolution and require a combination with single-cell RNA sequencing (scRNA-seq) information to deconvolute the spatially indexed datasets. Leveraging the strengths of both data types, we developed SPOTlight, a computational tool that enables the integration of ST with scRNA-seq data to infer the location of cell types and states within a complex tissue. SPOTlight is centered around a seeded non-negative matrix factorization (NMF) regression, initialized using cell-type marker genes and non-negative least squares (NNLS) to subsequently deconvolute ST capture locations (spots).

Analysis of alternative splicing and isoform switches with predicted functional consequences (e.g. gain/loss of protein domains etc.) from quantification of all types of RNA-seq (short/long) by tools such as Kallisto, Salmon, StringTie, Tallon, IsoQuant etc.