A novel method to prioritize RNAseq data for post-hoc analysis based on absolute changes in transcript abundance

Statistical Applications in Genetics and Molecular Biology
Patrick McNuttPhil Beske

Abstract

The use of fold-change (FC) to prioritize differentially expressed genes (DEGs) for post-hoc characterization is a common technique in the analysis of RNA sequencing datasets. However, the use of FC can overlook certain population of DEGs, such as high copy number transcripts which undergo metabolically expensive changes in expression yet fail to exceed the ratiometric FC cut-off, thereby missing potential important biological information. Here we evaluate an alternative approach to prioritizing RNAseq data based on absolute changes in normalized transcript counts (ΔT) between control and treatment conditions. In five pairwise comparisons with a wide range of effect sizes, rank-ordering of DEGs based on the magnitude of ΔT produced a power curve-like distribution, in which 4.7-5.0% of transcripts were responsible for 36-50% of the cumulative change. Thus, differential gene expression is characterized by the high production-cost expression of a small number of genes (large ΔT genes), while the differential expression of the majority of genes involves a much smaller metabolic investment by the cell. To determine whether the large ΔT datasets are representative of coordinated changes in the transcriptional program, we evaluated la...Continue Reading

References

Mar 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·A de PaivaJ O Dolly
Mar 11, 2003·Proceedings of the National Academy of Sciences of the United States of America·Michael P WashburnJohn R Yates
Jan 28, 2004·Annual Review of Pharmacology and Toxicology·Lance L Simpson
Sep 21, 2007·Bioinformatics·Mark D Robinson, Gordon K Smyth
Oct 20, 2007·Nature Protocols·Melissa S ClineGary D Bader
Dec 8, 2007·Blood·Raelene EndersbyJean-Philippe Lalonde
Jan 24, 2008·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Latasha C RedmondJoyce A Lloyd
May 3, 2008·Science·Ugrappa NagalakshmiMichael Snyder
Apr 18, 2009·The Journal of Pharmacology and Experimental Therapeutics·Julie A Coffield, Xiuzhen Yan
Apr 28, 2009·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Srividya Iyer-BiswasC Jayaprakash
Sep 4, 2009·Current Protocols in Bioinformatics·Da Wei HuangRichard A Lempicki
Jun 25, 2010·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·Daniel KrewskiLauren Zeise
Jan 11, 2011·Biochemical and Biophysical Research Communications·Patrick McNuttMariano Mesngon
May 20, 2011·Nature·Björn SchwanhäusserMatthias Selbach
Aug 6, 2011·Genome Research·Lichun JiangBrian Oliver
Sep 10, 2011·Genome Research·Sonia TarazonaAna Conesa
Jul 28, 2012·Genome Research·Michael R TallackAndrew C Perkins
Sep 19, 2012·Briefings in Bioinformatics·Marie-Agnès DilliesUNKNOWN French StatOmique Consortium
Mar 19, 2013·BMC Bioinformatics·Charlotte Soneson, Mauro Delorenzi
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders

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