Fig. 2.

Proposed integration pipeline for bulk chromatin and single-cell multiomics. The numbers in fields indicate the flow of proposed data integration pipelines for zebrafish regulatory genomics. Bulk chromatin multiomics integrates CRE classification information from ATAC-seq data (1) with CRE annotation information from ChIP-seq data to predict regulatory element function using the computational tool ChromHMM (2) (Baranasic et al., 2022). This feeds predicted developmental regulatory elements into PADREs (3). Single-cell ATAC-seq can then provide further cell cluster resolution (4) to allow cell-type assignment (5) (McGarvey et al., 2022). Integration of the bulk and single-cell data will reveal cell-type-specific CREs within PADREs (6). Alongside this, single-cell RNA-seq can reveal cell-type-specific TF binding (7), and sequence conservation tracks can identify disease-associated human CREs (8). Once the cell type, target gene, TF and TFBS have been defined (9), a mutant reporter zebrafish line can be generated to function as a model of a human disease (10). CNS, central nervous system; CRE, cis-regulatory element; EnhA1, active enhancer 1; EnhFlank, enhancer flanking; EnhWk1, weak enhancer; PADRE, predicted ATAC-seq-supported developmental regulatory element; Pois, poised; Quies, quiescent; ReprPC, repressed polycomb; sc-ATAC-seq, single-cell ATAC-seq; sc-RNA-seq, single-cell RNA sequencing; SNP, single-nucleotide polymorphism; TF, transcription factor; TFBS, transcription factor binding site; TssA1/2, active transcription start site 1/2; TssFlank1/2, TSS flanking.