Methods detecting rhythmic gene expression are biologically relevant only for strong signal.
Journal
PLoS computational biology
ISSN: 1553-7358
Titre abrégé: PLoS Comput Biol
Pays: United States
ID NLM: 101238922
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
22
08
2019
accepted:
18
01
2020
revised:
27
03
2020
pubmed:
18
3
2020
medline:
1
7
2020
entrez:
18
3
2020
Statut:
epublish
Résumé
The nycthemeral transcriptome embodies all genes displaying a rhythmic variation of their mRNAs periodically every 24 hours, including but not restricted to circadian genes. In this study, we show that the nycthemeral rhythmicity at the gene expression level is biologically functional and that this functionality is more conserved between orthologous genes than between random genes. We used this conservation of the rhythmic expression to assess the ability of seven methods (ARSER, Lomb Scargle, RAIN, JTK, empirical-JTK, GeneCycle, and meta2d) to detect rhythmic signal in gene expression. We have contrasted them to a naive method, not based on rhythmic parameters. By taking into account the tissue-specificity of rhythmic gene expression and different species comparisons, we show that no method is strongly favored. The results show that these methods designed for rhythm detection, in addition to having quite similar performances, are consistent only among genes with a strong rhythm signal. Rhythmic genes defined with a standard p-value threshold of 0.01 for instance, could include genes whose rhythmicity is biologically irrelevant. Although these results were dependent on the datasets used and the evolutionary distance between the species compared, we call for caution about the results of studies reporting or using large sets of rhythmic genes. Furthermore, given the analysis of the behaviors of the methods on real and randomized data, we recommend using primarily ARS, empJTK, or GeneCycle, which verify expectations of a classical distribution of p-values. Experimental design should also take into account the circumstances under which the methods seem more efficient, such as giving priority to biological replicates over the number of time-points, or to the number of time-points over the quality of the technique (microarray vs RNAseq). GeneCycle, and to a lesser extent empirical-JTK, might be the most robust method when applied to weakly informative datasets. Finally, our analyzes suggest that rhythmic genes are mainly highly expressed genes.
Identifiants
pubmed: 32182235
doi: 10.1371/journal.pcbi.1007666
pii: PCOMPBIOL-D-19-01419
pmc: PMC7100990
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1007666Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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