Group Heteroscedasticity - A Silent Saboteur of Power and False Discovery in RNA-Seq Differential Expression

Suvo Chatterjee, Arindam Fadikar, Vrushab Hanumesh, Siddhant Sunil Meshram, Roger S Zoh, Siyuan Ma, Ganesan Arunkumar, and Himel Mallick

bioRxiv preprint, 2024

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Abstract

This paper identifies group heteroscedasticity as an important and often overlooked source of false discovery rate inflation in RNA-Seq differential expression analysis.

The proposed Robseq framework uses robust M-estimation, heteroscedasticity-aware variance estimation, and Welch-type inferential adjustments to maintain nominal error rates while preserving power.

Simulation benchmarks and population-level analyses show robust control of false positives and improved detection of biologically meaningful pathways versus common DE pipelines.

Citation

BibTeX

@article{chatterjee2024robseq,
  title={Group Heteroscedasticity - A Silent Saboteur of Power and False Discovery in RNA-Seq Differential Expression},
  author={Chatterjee, Suvo and Fadikar, Arindam and Hanumesh, Vrushab and Meshram, Siddhant Sunil and Zoh, Roger S and Ma, Siyuan and Arunkumar, Ganesan and Mallick, Himel},
  journal={bioRxiv},
  year={2024},
  doi={10.1101/2024.04.01.587633},
  note={Preprint}
}