In zhiyuanhu/masonmd: Make Sense of Nonsense-Mediated Decay

1 Background

The package masonmd (MAke Sense Of NMD) can be used to predict the effect of nonsense-mediated decay on mutated genes. While some mutations can introduce premature termination codons (PTCs) into genes, nonsense mediated decay (NMD) can detect these PTCs and then eliminate the abnormal transcripts. PTCs and NMD play important roles in genetic diseases and cancers.

Herein, three rules are used to predict whether a PTC-generating mutation is NMD-elicit or NMD-escape: 1. PTC is more than 50-54bp upstream of the last-exon-exon junction. 2. targeted gene is not intronless. 3. PTC is more than 200bp downstream of the start codon.

Using this methods, we can predict whether a called mutation will elicit NMD on the mRNA from the mutated gene, i.e. the NMD-elicit mutations. For now, this package can only be used for human genomes.

2 Examples

This package is quite easy to use, with its main function classify.nmd. It reads in the information of called mutations/variants, and return the prediction results. The next two example mutations are from The Cancer Genome Atlas (TCGA).

The first example is a substitution mutation on AADAC (Entrez ID = 13). The mutation happened on the 151545640 site on chromosome from G to T. The mutation is called on NCBI-build 37.

library(masonmd)
# an example of NMD-escape mutation from TCGA
classify.nmd(gene_id = 13, ref = 37, mut_start = 151545640, mut_end = 151545640,
ref_nt = "G",mut_nt = "T")

The first entry of the return is mut_nmd = F, so it is not an NMD-elicit mutation. From the note and have.ptc = T. We can know that the mutation caused a PTC but did not trigger NMD, because it does not fulfill 50bp rule. The returned information also tell us: 1. whether the wildtype transcript is effected by NMD (wt_nmd) 1. relative position of PTC (PTC.stop), length of mutated coding sequence (mutseq_length), relative position of last exon-exon junction (last_exon_exon_junction) and number of exons (n.exon)

This information give the underlying of prediction results.

The second example is a NMD-elicit mutation in A2M gene (Entrez ID = 2).

# an example of NMD-elicit mutation from TCGA
classify.nmd(gene_id = 2, ref = 37, mut_start = 9221429, mut_end = 9221429,
ref_nt = "G", mut_nt = "A")

zhiyuanhu/masonmd documentation built on May 4, 2019, 11:22 p.m.