ArticleNature biotechnology2022
Massively parallel phenotyping of coding variants in cancer with Perturb-seq.
Article in Nature biotechnology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 60 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
60 citing papers in PubMed, 96 citations in OpenAlex.
- The GPCRDiabetologia · 2026Article
- Canon enables causal inference of downstream genes in single-cell CRISPR studies via instrumental variable analysis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A Comprehensive Review on CRISPR-Based Screening and Its Applications.Molecular biotechnology · 2026Review
- Image-based, pooled phenotyping reveals multidimensional, disease-specific variant effects.Cell · 2026Article
- Causal Prediction of TP53 Variant Pathogenicity Using a Perturbation-Informed Protein Language Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Multiplexed single-cell transcriptomics reveals diverse phenotypic outcomes for pathogenic SHP2 variants.Science advances · 2026Article
- Systematic mapping of chromatin dysregulation driven by viral transcriptional regulators at scale.bioRxiv : the preprint server for biology · 2026Article
- Massively parallel functional genomic assays in endocrinology: from promise to delivery.Journal of molecular endocrinology · 2026Review
- Disordered protein LAT encodes relative levels of signaling pathways in T cell activation.Science (New York, N.Y.) · 2026Article
- Nucleotide-resolution mapping of regulatory elements via allelic readout of tiled base editing.Nature communications · 2026Article
- Pooled single-cell screen in colorectal cancer defines transcriptional modules linked to oncogenes.Molecular systems biology · 2026Article
- Genome-wide single-cell perturbation screens with VIPerturb-seq.bioRxiv : the preprint server for biology · 2026Article
- The polygenic, omnigenic and stratagenic models of complex disease risk.Nature genetics · 2026Review
- Multiplexed assays of variant effect for clinical variant interpretation.Nature reviews. Genetics · 2026Review
- Phenotypic pleiotropy of missense variants in human B cell confinement receptor P2RY8.Cell genomics · 2025Article
- A cellular and spatial atlas of TP53-associated tissue remodeling defines a multicellular tumor ecosystem in lung adenocarcinoma.Nature cancer · 2025Article
- High-throughput evaluation of genetic variants with prime editing sensor libraries.Nature biotechnology · 2025Article
- Functional phenotyping of genomic variants using joint multiomic single-cell DNA-RNA sequencing.Nature methods · 2025Article
- PerturbNet predicts single-cell responses to unseen chemical and genetic perturbations.Molecular systems biology · 2025Article
- Massively parallel in vivo Perturb-seq screening.Nature protocols · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
21 authors at 2 institutions in 3 countries.
Funding
Abstract
Genome sequencing studies have identified millions of somatic variants in cancer, but it remains challenging to predict the phenotypic impact of most. Experimental approaches to distinguish impactful variants often use phenotypic assays that report on predefined gene-specific functional effects in bulk cell populations. Here, we develop an approach to functionally assess variant impact in single cells by pooled Perturb-seq. We measured the impact of 200 TP53 and KRAS variants on RNA profiles in over 300,000 single lung cancer cells, and used the profiles to categorize variants into phenotypic subsets to distinguish gain-of-function, loss-of-function and dominant negative variants, which we validated by comparison with orthogonal assays. We discovered that KRAS variants did not merely fit into discrete functional categories, but spanned a continuum of gain-of-function phenotypes, and that their functional impact could not have been predicted solely by their frequency in patient cohorts. Our work provides a scalable, gene-agnostic method for coding variant impact phenotyping, with potential applications in multiple disease settings.
Indexed as
Identifiers
What 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.