scQTLtools

Set of tools for evaluating pooled high-throughput screening experiments, typically employing CRISPR/Cas9 or shRNA expression cassettes. Contains methods for interrogating library and cassette behavior within an experiment, identifying differentially abundant cassettes, aggregating signals to identify candidate targets for empirical validation, hypothesis testing, and comprehensive reporting. Version 2.0 extends these applications to include a variety of tools for contextualizing and integrating signals across many experiments, incorporates extended signal enrichment methodologies via the "sparrow" package, and streamlines many formal requirements to aid in interpretablity.

The package clusters gene activity along chromosome into zones, detects differential zones as outstanding, and visualizes maps of outstanding zones across the genome. It enables characterization of effects on multiple genes within adaptive genomic neighborhoods, which could arise from genome reorganization, structural variation, or epigenome alteration. It guarantees cluster optimality, linear runtime to sample size, and reproducibility. One can apply it on genome-wide activity measurements such as copy number, transcriptomic, proteomic, and methylation data.

An implementation of a probabilistic modeling framework that jointly analyzes personal genome and transcriptome data to estimate the probability that a variant has regulatory impact in that individual. It is based on a generative model that assumes that genomic annotations, such as the location of a variant with respect to regulatory elements, determine the prior probability that variant is a functional regulatory variant, which is an unobserved variable. The functional regulatory variant status then influences whether nearby genes are likely to display outlier levels of gene expression in that person. See the RIVER website for more information, documentation and examples.

Recent advances in single cell/nucleus transcriptomic technology has enabled collection of cohort-scale datasets to study cell type specific gene expression differences associated disease state, stimulus, and genetic regulation. The scale of these data, complex study designs, and low read count per cell mean that characterizing cell type specific molecular mechanisms requires a user-frieldly, purpose-build analytical framework. We have developed the dreamlet package that applies a pseudobulk approach and fits a regression model for each gene and cell cluster to test differential expression across individuals associated with a trait of interest. Use of precision-weighted linear mixed models enables accounting for repeated measures study designs, high dimensional batch effects, and varying sequencing depth or observed cells per biosample.

Provides an interface to several normalization and statistical testing packages for RNA-Seq gene expression data. Additionally, it creates several diagnostic plots, performs meta-analysis by combinining the results of several statistical tests and reports the results in an interactive way.

Crumblr enables analysis of count ratio data using precision weighted linear (mixed) models. It uses an asymptotic normal approximation of the variance following the centered log ration transform (CLR) that is widely used in compositional data analysis. Crumblr provides a fast, flexible alternative to GLMs and GLMM's while retaining high power and controlling the false positive rate.