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Confounders of lncRNA screens: sources, consequences and possible solutions

Nature Methods Bioinformatics AI Juan José Montero, Riccardo Trozzo, Roland Rad 2026-08-31

TL;DR - A Nature Methods analysis warns that high-throughput lncRNA perturbation screens can produce unexpectedly high false-positive rates due to technical and analytical confounders. Identifying and mitigating these artifacts is essential for reliable conclusions about lncRNA function.

  • Re-analysis of published lncRNA screens uncovered high false-positive rates in some studies.
  • Genetic perturbation screens appear more susceptible to methodological artifacts for lncRNAs than for protein-coding genes.
  • The article identifies common technical and analytical sources of spurious findings.
  • It outlines strategies to detect, monitor, and mitigate confounders in future screens.

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