Genetic Convergence Analysis of CRISPR Perturbations Deciphers Gene Functional Similarity.

ABSTRACT: Pooled CRISPR screens with single-cell RNA sequencing readout (Perturb-seq) have emerged as a key technique to determine the functionality of a gene by directly perturbing the DNA of the gene. One of the most intriguing recent problems is quantifying the similarity between CRISPR perturbations, for example, whether they upregulate the same set of downstream genes. In this context, genetic convergence refers to the phenomenon where CRISPR disruptions of different genes lead to a similar downstream outcome. Existing methods are mostly heuristic. We present XConTest, a two-step, cross-validated procedure for assessing the genetic convergence problem. The test statistics calculated from that procedure are approximately standard normal when the two perturbations have an orthogonal influence on

SUBMITTER: Zhang T 

PROVIDER: S-EPMC12642637 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature