Gene-level differential analysis at transcript-level resolution

Genome Biology
Lynn YiLior Pachter


Compared to RNA-sequencing transcript differential analysis, gene-level differential expression analysis is more robust and experimentally actionable. However, the use of gene counts for statistical analysis can mask transcript-level dynamics. We demonstrate that 'analysis first, aggregation second,' where the p values derived from transcript analysis are aggregated to obtain gene-level results, increase sensitivity and accuracy. The method we propose can also be applied to transcript compatibility counts obtained from pseudoalignment of reads, which circumvents the need for quantification and is fast, accurate, and model-free. The method generalizes to various levels of biology and we showcase an application to gene ontologies.


Sep 8, 2020·ELife·Chiara SinigagliaLucas Leclère
Nov 14, 2019·Journal of Clinical Medicine·Claudia De VitisRita Mancini
Jun 3, 2020·Nature Methods·Etienne BechtRaphael Gottardo
Oct 28, 2019·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Ibrahim A AkkouhTimothy Hughes
Aug 15, 2019·BMC Bioinformatics·Mohamed K GunadyHéctor Corrada Bravo
Jan 27, 2019·Scientific Reports·Sunghee OhRobert W Li


Nov 19, 2008·Nature Reviews. Genetics·Zhong WangMichael Snyder
Oct 29, 2010·Genome Biology·Simon Anders, Wolfgang Huber
Jun 23, 2012·Genome Research·Simon AndersWolfgang Huber
Dec 12, 2012·Nature Biotechnology·Cole TrapnellLior Pachter
Jul 23, 2013·Nature Protocols·Huaiyu MiPaul D Thomas
Sep 17, 2013·Nature·Tuuli LappalainenEmmanouil T Dermitzakis
Sep 28, 2014·Bioinformatics·Simon AndersWolfgang Huber
Nov 28, 2014·Nucleic Acids Research·Gene Ontology Consortium
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders
Jan 26, 2016·PLoS Computational Biology·David LamparterSven Bergmann
Apr 5, 2016·Nature Biotechnology·Nicolas L BrayLior Pachter
Apr 1, 2017·American Journal of Respiratory Cell and Molecular Biology·Tamas DolinaySusan S Margulies
Jun 6, 2017·Nature Methods·Harold PimentelLior Pachter

Related Concepts

Sequence Determinations, RNA
Analysis of Substances
Gene Ontology Project
Gene Expression Analysis
Gene Ontology

Related Feeds

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.