CROTONdb: variant effect prediction database for CRISPR/Cas9 editing outcomes.

CRISPR/Cas9 is a revolutionary gene-editing technology that has been widely utilized in biology, biotechnology, and medicine. Increasingly, this state of the art gene-editing technology is being applied to human samples. For basic biological research, CRISPR/Cas9 is often utilized in primary cell lines derived from human donors. Primary cells are ubiquitous in biomedicine, and they have been used in fields ranging from virology to cell therapy, vaccine production, and drug screening. In addition, in the clinic, therapies that involve CRISPR/Cas9-mediated editing of cells derived from patients have been deemed safe and feasible. These therapies involve the correction of genetic deficiencies as well as the engineering of patient-derived cell lines to target disease.

The human population contains a large amount of genomic variation. A major subset of human genetic diversity are single nucleotide variants (SNVs). Indeed, there are 10 to 15 million common SNVs present in the human population. Since CRISPR/Cas9 editing outcomes are dependent on the genomic context of target sequences, these common variants have the potential to significantly affect the outcomes of CRISPR/Cas9-based editing. However, the effect of genetic alterations on CRISPR/Cas9 editing outcomes has not been systematically studied or documented, even as CRISPR/Cas9 is increasingly applied to primary cells and patient samples that may harbor such genetic diversity.

Any researcher or clinician looking to apply CRISPR/Cas9 editing in samples that may harbor genomic variation can reference our website to guide their target sequence selection. Whether in the laboratory or the clinic, our model has broad applications in ensuring CRISPR/Cas9-based studies or treatments are consistent, effective, and equitable.