DNA methylation indices of exposure and phenotype (meffonym)

Installation

library(remotes)
install_github("perishky/meffonym")

Typical use

In the example below, we show how to apply the Hannum clock (Hannum et al. 2013).

library(meffonym)

meth <- ... ## methylation matrix, rows=CpG site, columns=samples
age <- ... ## age for each sample
female <- ... ## sex for each sample (1=female,0=male)

ret <- meffonym.score(meth, "hannum")

cor(ret$score, age)
## [1] 0.9342

Special cases

Some models require additional inputs or have optional steps:

• The original epigenetic clock, Horvath DNAmAge ('horvath' model) includes an optional normalization step using the BMIQ algorithm and a DNA methylation 'gold standard' (http://labs.genetics.ucla.edu/horvath/dnamage/probeAnnotation21kdatMethUsed.csv). This can be achieved here by setting the calibrate parameter to TRUE in meffonym.score() or by using the meffonym.horvath.age() function.

meffonym.score(meth,"horvath",calibrate=TRUE)$score
== meffonym.horvath.age(meth)

• Similarly, DunedinPACE ('dunedinpace' model) allows a similar optional normalization step using a standard (from https://github.com/danbelsky/DunedinPACE). This can be achieved here by setting the calibrate parameter to TRUE in meffonym.score() or by using the meffonym.dunedinpace.estimate() function.

meffonym.score(meth, "dunedinpace", calibrate=TRUE)$score
== meffonym.dunedinpace.estimate(meth)

• The Grimage model ('grimage' and 'grimagev2') includes sex and age in addition to DNA methylation. These can be specified either by adding additional rows called 'female' (1 if female and 0 of male) and 'age' to the data matrix passed to meffonym.score(). Alternatively, the meffonym.grimage() function can be used.

meffonym.score(rbind(meth,female=female,age=age))$score
== meffonym.grimage(meth,female,age)

• A few clocks apply a log-transformation to linear model estimates. This is default behavior by meffonym.score() for the Horvath DNAmAge ('horvath'), Skin and Blood ('skin') and PedBE ('pedbe') models. This behavior can be changed for all clocks by passing an alterative transformation function to the transform parameter.

Current list of models

models.csv

For developers

Models can be added temporarily to the package using meffonym.add.models(). However, these models will disappear as soon as R is exited or meffonym is reloaded. To add a model so that it persists, create a new folder and add the model definition to inst and add a new row for the model in inst/models.csv. The model definition is encoded in a csv file with two columns, pred.var and coef. One row can optionally provide a model intercept with the pred.var name 'intercept'.

Models to add

• Shokhirev MN, Torosin NS, Kramer DJ, Johnson AA, Cuellar TL. CheekAge: a next-generation buccal epigenetic aging clock associated with lifestyle and health. Geroscience. 2024 Jun;46(3):3429-3443.
• Smith HM, Ng HK, Moodie JE, Gadd DA, McCartney DL, Bernabeu E, Campbell A, Redmond P, Taylor A, Page D, Corley J, Harris SE, Tay D, Deary IJ, Evans KL, Robinson MR, Chambers JC, Loh M, Cox SR, Marioni RE, Hillary RF. Methylome-wide studies of six metabolic traits. medRxiv [Preprint]. 2024 May 29:2024.05.29.24308103. doi: 10.1101/2024.05.29.24308103.
• Li X, Zhang Y, Gao X, Holleczek B, Schottker B, Brenner H. Comparative validation of three DNA methylation algorithms of ageing and a frailty index in relation to mortality: results from the ESTHER cohort study. EBioMedicine. 2021;74 doi: 10.1016/j.ebiom.2021.103686.