Author: You Zhou, Kathi Zarnack
N6-methyladenosine (m6A) is the most abundant internal modification in mRNA.
It impacts many different aspects of an mRNA's life, e.g. nuclear export,
translation, stability, etc.
m6A individual-nucleotide resolution UV crosslinking and immunoprecipitation
(miCLIP) and the improved **miCLIP2** are m6A antibody-based methods that allow
the transcriptome-wide mapping of m6A sites at a single-nucleotide resolution.
In brief, UV crosslinking of the m6A antibody to
the modified RNA leads to truncation of reverse transcription or C-to-T
transitions in the case of readthrough. However, due to the limited specificity
and high cross-reactivity of the m6A antibodies, the miCLIP data comprise a
high background signal, which hampers the reliable identification of m6A sites
from the data.
For accurately detecting m6A sites, we implemented an AdaBoost-based machine
learning model (**m6Aboost**) for classifying the miCLIP2 peaks into m6A sites
and background signals. The model was trained on high-confidence
m6A sites that were obtained by comparing wildtype and _Mettl3_ knockout mouse
embryonic stem cells (mESC) lacking the major methyltransferase Mettl3. For
classification, the m6Aboost model uses a series of features, including the
experimental miCLIP2 signal (truncation events and C-to-T transitions) as well
as the transcript region (5'UTR, CDS, 3'UTR) and the nucleotide sequence in a
21-nt window around the miCLIP2 peak.
The package [m6Aboost](http://bioconductor.org/packages/m6Aboost) includes the
trained model and the functionalities to prepare the data, extract the
required features and predict the m6A sites.
## Citing m6Aboost
> Körtel, Nadine#, Cornelia Rückle#, You Zhou#, Anke Busch, Peter Hoch-Kraft,
FX Reymond Sutandy, Jacob Haase, et al. 2021. “Deep and accurate detection
of m6A RNA modifications using miCLIP2 and m6Aboost machine learning.”
## How to use it
Documentation (vignette and user manual) is available at the **m6Aboost's**
Bioconductor landing page at http://bioconductor.org/packages/m6Aboost.