ArticleCell reports methods2024
Single-cell RNA sequencing algorithms underestimate changes in transcriptional noise compared to single-molecule RNA imaging.
Article in Cell reports methods, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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Who cites it
7 citing papers in PubMed.
- Rapid Transcription Dynamics Confers Cytarabine Resistance in Acute Myeloid Leukemia.Blood cancer discovery · 2026Article
- Integrating the Contrasting Perspectives Between the Constrained Disorder Principle and Deterministic Optical Nanoscopy: Enhancing Information Extraction from Imaging of Complex Systems.Bioengineering (Basel, Switzerland) · 2026Article
- Enhanced MiRISC expression noise reduction by self-feedback regulation of mRNA degradation.Computational and structural biotechnology journal · 2026Article
- How cells tame noise while maintaining ultrasensitive transcriptional responses.PLoS computational biology · 2025Article
- Investigating Gene Expression Noise Reduction by MicroRNAs and MiRISC Reinforcement by Self-Feedback Regulation of mRNA Degradation.bioRxiv : the preprint server for biology · 2025Article
- TrueProbes: Quantitative Single-Molecule RNA-FISH Probe Design Improves RNA Detection.bioRxiv : the preprint server for biology · 2025Article
- Single-cell analyses reveal increased gene expression variability in human neurodevelopmental conditions.American journal of human genetics · 2025Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Stochastic fluctuations (noise) in transcription generate substantial cell-to-cell variability. However, how best to quantify genome-wide noise remains unclear. Here, we utilize a small-molecule perturbation (5'-iodo-2'-deoxyuridine [IdU]) to amplify noise and assess noise quantification from numerous single-cell RNA sequencing (scRNA-seq) algorithms on human and mouse datasets and then compare it to noise quantification from single-molecule RNA fluorescence in situ hybridization (smFISH) for a panel of representative genes. We find that various scRNA-seq analyses report amplified noise-without altered mean expression levels-for ∼90% of genes and that smFISH analysis verifies noise amplification for the vast majority of tested genes. Collectively, the analyses suggest that most scRNA-seq algorithms (including a simple normalization approach) are appropriate for quantifying noise, although all algorithms appear to systematically underestimate noise changes compared to smFISH. For practical purposes, this analysis further argues that IdU noise enhancement is globally penetrant-i.e., homeostatically increasing noise without altering mean expression levels-and could enable investigations of the physiological impacts of transcriptional noise.
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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 Socratic graph.