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Fold change is a measure describing how much a quantity changes between an original and a subsequent measurement. It is defined as the ratio between the two quantities; for quantities A and B the fold change of B with respect to A is B/A. In other words, a change from 30 to 60 is defined as a fold-change of 2. This is also referred to as a "one fold increase". Similarly, a change from 30 to 15 is referred to as a "0.5-fold decrease". Fold change is often used when analysing multiple measurements of a biological system taken at different times as the change described by the ratio between the time points is easier to interpret than the difference.
Fold change is so called because it is common to describe an increase of multiple X as an "X-fold increase". As such, several dictionaries, including the Oxford English Dictionary[1] and Merriam-Webster Dictionary,[2] as well as Collins's Dictionary of Mathematics, define "-fold" to mean "times", as in "2-fold" = "2 times" = "double". Likely because of this definition, many scientists use not only "fold", but also "fold change" to be synonymous with "times", as in "3-fold larger" = "3 times larger".[3][4][5]
Fold change is often used in analysis of gene expression data from microarray and RNA-Seq experiments for measuring change in the expression level of a gene.[6] A disadvantage and serious risk of using fold change in this setting is that it is biased[7] and may misclassify differentially expressed genes with large differences (B − A) but small ratios (B/A), leading to poor identification of changes at high expression levels. Furthermore, when the denominator is close to zero, the ratio is not stable, and the fold change value can be disproportionately affected by measurement noise.
^"Free OED – Oxford English Dictionary".
^"Definition of TWOFOLD". 22 March 2024.
^Cieńska, M.; Labus, K.; Lewańczuk, M.; Koźlecki, T.; Liesiene, J.; Bryjak, J. (2016). "Effective L-Tyrosine Hydroxylation by Native and Immobilized Tyrosinase". PLOS ONE. 11 (10): e0164213. Bibcode:2016PLoSO..1164213C. doi:10.1371/journal.pone.0164213. PMC 5053437. PMID 27711193.
^Cunningham, M. W. Jr.; Williams, J. M.; Amaral, L.; Usry, N.; Wallukat, G.; Dechend, R.; LaMarca, B. (2016). "Agonistic Autoantibodies to the Angiotensin II Type 1 Receptor Enhance Angiotensin II–Induced Renal Vascular Sensitivity and Reduce Renal Function During Pregnancy". Hypertension. 68 (5): 1308–1313. doi:10.1161/HYPERTENSIONAHA.116.07971. PMC 5142826. PMID 27698062.
^Li, B.; Li, Y. Y.; Wu, H. M.; Zhang, F. F.; Li, C. J.; Li, X. X.; Lambers, H.; Li, L. (2015). "Root exudates drive interspecific facilitation by enhancing nodulation and N2 fixation". PNAS. 113 (23): 6496–6501. doi:10.1073/pnas.1523580113. PMC 4988560. PMID 27217575.
^Tusher, Virginia Goss; Tibshirani, Robert; Chu, Gilbert (2001). "Significance analysis of microarrays applied to the ionizing radiation response". Proceedings of the National Academy of Sciences of the United States of America. 98 (18): 5116–5121. Bibcode:2001PNAS...98.5116T. doi:10.1073/pnas.091062498. PMC 33173. PMID 11309499.
^Mariani, T. J.; Budhraja V.; Mecham B. H.; Gu C. C.; Watson M. A.; Sadovsky Y. (2003). "A variable fold change threshold determines significance for expression microarrays". FASEB J. 17 (2): 321–323. doi:10.1096/fj.02-0351fje. PMID 12475896. S2CID 16668234.
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