SCREE

SCREE analyzes single-cell multi-modal CRISPR screen data to integrate RNA sequencing (RNA-seq), Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) and other modalities and quantify perturbation effects for gene regulatory circuit inference.

Key Features:

• Comprehensive Data Handling: Processes diverse single-cell CRISPR screen readouts including RNA-seq, ATAC-seq and other multimodal data.
• Read Alignment and sgRNA Assignment: Performs read alignment to reference genomes and assigns single-guide RNAs (sgRNAs) to cells.
• Quality Control: Implements stringent quality-control steps to assess data integrity for single-cell modalities.
• Clustering and Visualization: Groups similar cells via clustering and provides visualization of cellular states and perturbation effects.
• Enrichment Evaluation: Assesses enrichment of perturbations across cell populations to identify significant effects.
• Efficiency Modeling: Models the efficiency of genetic perturbations to estimate on-target impact.
• Gene Regulatory Score Calculation: Computes scores reflecting gene regulatory changes induced by CRISPR perturbations.
• Functional Analyses: Supports downstream functional analyses to link perturbations to biological pathways and phenotypes.

Scientific Applications:

• Gene regulatory network inference: Enables inference of gene regulatory circuits at single-cell resolution using CRISPR perturbations.
• Multi-omic perturbation impact assessment: Evaluates effects of genetic perturbations on chromatin accessibility, gene expression, and protein-related readouts.
• Cellular heterogeneity analysis: Explores heterogeneity in responses to perturbations to investigate disease mechanisms and therapeutic hypotheses.

Methodology:

Read alignment to reference genomes; sgRNA assignment to cells; quality control of single-cell RNA-seq, ATAC-seq and multimodal data; clustering and visualization; enrichment evaluation of perturbations; efficiency modeling of genetic perturbations; and calculation of gene regulatory scores.