Resources

Methods and tools we built to share.

Open models, code, protocols, and datasets from the lab — for predicting enhancer–gene regulation, running CRISPR screens, and studying RNA. Everything links to the browser, repository, or paper where you can start using it.

Enhancer–gene regulation

Linking enhancers to target genes

We build computational models that predict which enhancers regulate which genes across thousands of cell types and tissues, and we host the resulting maps in interactive browsers.

E2G Browser — explore predicted enhancer–gene links
IGVF Catalog — variant-to-function data from the IGVF consortium
ENCODE-rE2G model — predicts enhancer–gene links from bulk ATAC / DNase / H3K27ac / Hi-C
scE2G model — single-cell ATAC / multiome predictions
ABC model — the Activity-by-Contact model (see below)

Benchmarking pipelines

Related papers on the Publications page, including the ENCODE enhancer–gene encyclopedia and scE2G.

Model

Activity-by-Contact (ABC) model

The ABC model predicts enhancer–gene regulatory interactions by combining measurements of enhancer activity and 3D contact frequency. We have applied it to generate predictions across 131 cell types and tissues, with pipeline outputs, an interactive browser, and curated CRISPR validation datasets.

Schematic of the Activity-by-Contact model: enhancer activity times enhancer–promoter contact predicts regulatory-element-to-gene connections across hundreds of cell types.

ABC predictions browser — predictions across 131 biosamples
ABC model code

Key papers — Fulco & Nasser et al., Nature Genetics (2019) and Nasser et al., Nature (2021). See also the Publications page.

Method

CRISPRi tiling & FlowFISH

We use CRISPR interference (CRISPRi) together with RNA FlowFISH to map how noncoding elements control gene expression at scale. Below are the plasmids, screen-design resources, and analysis code.

CRISPRi tiling with FlowFISH: KRAB-dCas9 and a tiling gRNA library target DHS peaks, cells are stained by RNA FISH for the gene of interest, sorted by expression into six bins, and gRNAs sequenced to infer each element's effect.

AddGene plasmids
CRISPR screen design checklist (Google Doc)
CRISPRi tiling gRNA design tool
CRISPRi-FlowFISH analysis code

Key papers — Fulco & Nasser et al., Nature Genetics (2019) and Fulco et al., Science (2016). See the Publications page.

Method

RNA Antisense Purification (RAP)

RAP is a biochemical method to identify the DNA, RNA, and proteins associated with a specific RNA of interest, developed together with the Guttman Lab.

RNA Antisense Purification workflow: crosslinked cells are lysed, biotinylated probes hybridize to the target RNA, and captured complexes are eluted for DNA sequencing, RNA sequencing, or mass spectrometry.

RAP-DNA and RAP-RNA protocol (PDF)
Probe design tool (Guttman Lab)

Key papers — Engreitz et al., Cell (2014) and Engreitz et al., Science (2013). See the Publications page.