CPA-Perturb-seq: Multiplexed single-cell characterization of alternative polyadenylation regulators.

Most mammalian genes have multiple polyA sites, representing a substantial source of transcript diversity that is governed by the cleavage and polyadenylation (CPA) regulatory machinery. To better understand how these proteins govern polyA site choice we introduce CPA-Perturb-seq, a multiplexed perturbation screen dataset of 42 known CPA regulators with a 3' scRNA-seq readout that enables transcriptome-wide inference of polyA site usage. We develop a statistical framework to specifically identify perturbation-dependent changes in intronic and tandem polyadenylation, and discover modules of co-regulated polyA sites exhibiting distinct functional properties. By training a multi-task deep neural network (APARENT-Perturb) on our dataset, we delineate a

Déclaration de conflit d'intérêts

COMPETING INTERESTS In the past three years, R.S. has worked as a consultant for Bristol-Myers Squibb, Regeneron, and Kallyope and served as an SAB member for ImmunAI, Resolve Biosciences, Nanostring, and the NYC Pandemic Response Lab. A.K. is on the SAB of PatchBio Inc., SerImmune Inc., AINovo Inc., TensorBio Inc., and OpenTargets; was a consultant with Illumina Inc. until Jan 2023; and owns shares in DeepGenomics Inc., Immunai Inc. and Freenome Inc. J.L. is an employee of Calico Life Sciences LLC as of 11/21/2022.