cicero

Cicero computes putative cis-regulatory maps from single-cell chromatin accessibility data by identifying co-accessible pairs of DNA elements to connect regulatory elements to their putative target genes.

Key Features:

• Cis-regulatory interaction prediction: Cicero identifies co-accessible pairs of DNA elements using single-cell chromatin accessibility data to infer connections between regulatory elements and their putative target genes.
• Monocle 2 extension: Cicero extends monocle 2 for use in chromatin accessibility data, enabling pseudotemporal analysis of chromatin state dynamics.
• Chromatin hub characterization: Cicero-linked regulatory elements are enriched for physical proximity, interact with a common set of transcription factors, and undergo coordinated changes in histone marks predictive of gene expression changes.

Scientific Applications:

• Differentiation studies: Cicero investigates how dynamically accessible elements orchestrate gene regulation during cellular differentiation, as demonstrated in differentiating myoblasts.
• Transcription factor dependency analysis: Cicero identifies element subsets bound by specific transcription factors, such as MYOD1, and their dependent opening mechanisms involving factors like PBX1 and MEIS1.
• Genome-wide cis-regulation dissection: Cicero enables analysis of the architecture, sequence determinants, and mechanisms of cis-regulation on a genome-wide scale.

Methodology:

Cicero uses an algorithm that identifies co-accessible pairs of DNA elements from single-cell chromatin accessibility data to predict cis-regulatory DNA interactions.