ArticlePLoS biology2017
Evaluation of RNAi and CRISPR technologies by large-scale gene expression profiling in the Connectivity Map.
Article in PLoS biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 1 of them a synthesis that pooled it.
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
112 citing papers in PubMed, 1 synthesis or guideline pooled it, 178 citations in OpenAlex.
- Synthetic lethal gene pairs: Experimental approaches and predictive models.Frontiers in genetics · 2022Pooled it
- CRISPR/Cas Systems: Biological Basis and Genome Editing Applications.Methods in molecular biology (Clifton, N.J.) · 2027Review
- Testing the Transferability of Perturbational Similarity Maps Across Species, Cell Systems, and Assay Modalities.Neuroinformatics · 2026Article
- In Vivo CRISPR Interference Screen Reveals Long Noncoding RNA Portfolio Crucial for Cutaneous Squamous Cell Carcinoma Tumor Growth.The Journal of investigative dermatology · 2026Article
- NCES: A Cell-Specific Network-Augmented Essentiality Framework for Cancer Therapeutic Target Discovery.Computational and structural biotechnology journal · 2026Article
- Gene Editing of Pluripotent Stem Cell-Derived Hepatic Cells for Liver Disease Modeling and Therapeutic Development.Biomolecules & therapeutics · 2026Review
- Adeno-associated viral vector resource for the RNA-targeting Cas13d: A comparison of high-fidelity variants, DjCas13d and hfCas13d.Molecular therapy. Methods & clinical development · 2025Article
- Sialyl-T Antigen: A Novel Red Blood Cell Determinant for Plasmodium falciparum Invasion.American journal of hematology · 2025Article
- Cell-type-agnostic differential gene expression uncovers conserved principles of cellular regulation.bioRxiv : the preprint server for biology · 2025Article
- GeneRAIN: multifaceted representation of genes via deep learning of gene expression networks.Genome biology · 2025Article
- Exploring the omnigenic architecture of selected complex traits.American journal of human genetics · 2025Article
- CRISPR-Cas9 mediated RALA knockout and reconstitution: insights into the detection and role of RALA S194 phosphorylation in Ras-dependent and Ras-independent cancers.Biology open · 2025Article
- CRISPR/Cas-mediated mRNA knockdown in the embryos of Xenopus tropicalis.Cell & bioscience · 2025Article
- PRODE recovers essential and context-essential genes through neighborhood-informed scores.Genome biology · 2025Article
- Arrayed CRISPRi library to suppress genes required for Schizosaccharomyces pombe viability.The Journal of cell biology · 2025Article
- Synthetic lethal strategies for the development of cancer therapeutics.Nature reviews. Clinical oncology · 2025Review
- Systemic evaluation of various CRISPR/Cas13 orthologs for knockdown of targeted transcripts in plants.Genome biology · 2024Article
- CRISPR-based genetic screens advance cancer immunology.Science China. Life sciences · 2024Review
- NP-TCMtarget: a network pharmacology platform for exploring mechanisms of action of traditional Chinese medicine.Briefings in bioinformatics · 2024Article
- Drug-target interaction prediction by integrating heterogeneous information with mutual attention network.BMC bioinformatics · 2024Article
52 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
The application of RNA interference (RNAi) to mammalian cells has provided the means to perform phenotypic screens to determine the functions of genes. Although RNAi has revolutionized loss-of-function genetic experiments, it has been difficult to systematically assess the prevalence and consequences of off-target effects. The Connectivity Map (CMAP) represents an unprecedented resource to study the gene expression consequences of expressing short hairpin RNAs (shRNAs). Analysis of signatures for over 13,000 shRNAs applied in 9 cell lines revealed that microRNA (miRNA)-like off-target effects of RNAi are far stronger and more pervasive than generally appreciated. We show that mitigating off-target effects is feasible in these datasets via computational methodologies to produce a consensus gene signature (CGS). In addition, we compared RNAi technology to clustered regularly interspaced short palindromic repeat (CRISPR)-based knockout by analysis of 373 single guide RNAs (sgRNAs) in 6 cells lines and show that the on-target efficacies are comparable, but CRISPR technology is far less susceptible to systematic off-target effects. These results will help guide the proper use and analysis of loss-of-function reagents for the determination of gene function.
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.