Epigenetic marks include modifications to the four DNA nucleotides (adenosine, thymine, cytosine and guanine) encoding another level of information affecting how cells express genes. Cytosine methylation (mC) is a fundamental regulatory mechanism and perturbation is implicated in several diseases . Hydroxymethyl-cytosine (hmC), the oxidised form of methyl-cytosine (mC), is a stable epigenetic mark in its own right; however, current sequencing methods do not distinguish mC and hmC and so miss the regulatory role of hmC and, crucially, its potential as a biomarker. Methylation has been shown to be of particular importance in in the placenta , and has been linked to conditions such as preeclampsia .
The project will involve the computational analysis of next-generation sequencing methylation data and the development of novel statistical methods to accurately determine the relative proportions of methyl-cytosine and hydroxymethyl-cytosine across cohort studies. Distinguishing these distinct methylation marks is key to future biomarker discovery.
1. Jones, P. A. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat. Rev. Genet. 13, 484–92 (2012).
2. Branco, M. R. et al. Maternal DNA Methylation Regulates Early Trophoblast Development Article Maternal DNA Methylation Regulates. Dev. Cell 36, 152–163 (2016).
3. Schroeder, D. I. et al. The human placenta methylome. Proc. Natl. Acad. Sci. U. S. A. 110, 6037–42 (2013).