Long-read sequencing (LRS) has revealed a far greater diversity of RNA isoforms than earlier technologies, increasing the critical need to determine which, and how many, isoforms per gene are biologic...

Allele-specific quantification of sequencing data, such as gene expression, allows for a causal investigation of how DNA sequence variations influence cis gene regulation. Current methods for analyzin...

An engineered Cas12a enables higher-order combinatorial functional genomic screens using CRISPR interference.

The substrate(s) of most E3 ubiquitin ligases remain unknown. Suiter et al. present COMET, a combinatorial framework for identifying proteolytic E3-substrate relationships at scale. Deep-learning-base...

Large genome rearrangements in mammalian cells can be generated at scale

Simultaneous profiling of the genome, methylome, epigenome and transcriptome using single-molecule chromatin fiber sequencing and multiplexed arrays isoform sequencing identifies the genetic and molec...

We developed PRINT, a computational method that identifies footprints of DNA–protein interactions from bulk and single-cell chromatin accessibility data across multiple scales of protein size.

Large-scale experimental analysis of Human Domainome 1, a library containing more than 500,000 missense mutation variants across more than 500 human protein domains, reveals that 60% of pathogenic mis...

A foundation model learns transcriptional regulatory syntax from chromatin accessibility and sequence data across a range of cell types to predict gene expression and transcription factor interactions...

Despite extensive mapping of cis-regulatory elements (cREs) across cellular contexts with chromatin accessibility assays, the sequence syntax and genetic variants that regulate transcription factor (T...

Standard genome-wide association studies (GWAS) and rare variant burden tests are essential tools for identifying trait-relevant genes. Although these methods are conceptually similar, we show by anal...