ArticleNature biotechnology2025
Saturation profiling of drug-resistant genetic variants using prime editing.
Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed.
- cPRIME enables endogenous mapping of genetic variant effects at RNA level.Nature communications · 2026Article
- Article
- Deciphering protein mutation-phenotype linkages from CRISPR-based tiling mutagenesis screens.Cell systems · 2026Article
- Compound delivery of eVLPs enhances prime editing for targeted genome engineering and high-throughput screening.Cell genomics · 2026Article
- Comprehensive resistance profiling of chronic myeloid leukaemia associated ABL1 variants against five tyrosine kinase inhibitors using prime editing.Nature biomedical engineering · 2026Article
- Uncovering functional variants using a high-efficiency PE3-based screening platform.Science advances · 2026Article
- A multiplex, prime editing framework for identifying drug resistance variants at scale.Cell genomics · 2026Article
- High-resolution functional mapping of androgen receptor variants.Nature biomedical engineering · 2026Article
- Systematic pegRNA design with PRIDICT2.0 and ePRIDICT for efficient prime editing.Nature protocols · 2026Review
- Prime Editing Driven Functional Genomics: Bridging Genotype to Phenotype in the Post-Genomic Era.International journal of molecular sciences · 2026Review
- Decoding efficacy and resistance space at a drug binding site.Nature communications · 2026Article
- A comprehensive functional atlas of ALK kinase domain variants reveals resistance landscape to ALK inhibitors.Genome biology · 2026Article
- LDLR variant classification through activity-normalized prime editing screening.bioRxiv : the preprint server for biology · 2025Article
- A functional map of CDK-drug interactions at single amino acid resolution.bioRxiv : the preprint server for biology · 2025Article
- Characterizing Variants of Uncertain Drug Resistance (VUDRs) Using Quantitative Measurements at Clinical Exposures.bioRxiv : the preprint server for biology · 2025Article
- Fueling chromosomal gene diversification and artificial evolution with CRISPR.Genome biology · 2025Review
- Perturbomics: CRISPR-Cas screening-based functional genomics approach for drug target discovery.Experimental & molecular medicine · 2025Review
- High-throughput screening of human genetic variants by pooled prime editing.Cell genomics · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
Methods to characterize the functional effects of genetic variants of uncertain significance (VUSs) have been limited by incomplete coverage of the mutational space. In clinical oncology, drug resistance arising from VUSs can prevent optimal treatment. Here we introduce PEER-seq, a high-throughput method based on prime editing that can evaluate the functional effects of single-nucleotide variants (SNVs). PEER-seq introduces both intended SNVs and synonymous marker mutations using prime editing and deep sequences the endogenous target regions to identify the introduced SNVs. We generate and functionally evaluate 2,476 SNVs in the epidermal growth factor receptor gene (EGFR), including 99% of all possible variants in the canonical tyrosine kinase domain. We determined resistance profiles of 95% of all possible EGFR protein variants encoded in the whole tyrosine kinase domain against the common tyrosine kinase inhibitors afatinib, osimertinib and osimertinib in the presence of the co-occurring substitution T790M, in PC-9 cells. Our study has the potential to substantially improve the precision of therapeutic choices in clinical settings.
Indexed as
Identifiers
39533107What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.