HyPhy-MEME

What question does this method answer?

Which site(s) in a gene are subject to pervasive or episodic, i.e. only on a single lineage or subset of lineages, diversifying selection?

Recommended Applications

The phenomenon of pervasive selection is generally most prevalent in pathogen evolution and any biological system influenced by evolutionary arms race dynamics (or balancing selection), including adaptive immune escape by viruses. MEME is ideally suited to identify sites under positive selection which represent candidate sites subject to strong selective pressures across the entire phylogeny or only on parts of the phylogeny.

MEME is the sole method in HyPhy for detecting selection at individual sites that considers both pervasive and episodic selection. MEME is therefore our recommended method if maximum power is desired.

Brief description

MEME (Mixed Effects Model of Evolution) estimates a site-wise synonymous (alpha) and a two-category mixture of non-synonymous (beta-, with proportion p-, and beta+ with proportion [1-p-]) rates, and uses a likelihood ratio test to determine if beta+ > α at a site. The estimates aggregate information over a proportion of branches at a site, so the signal is derived from episodic diversification, which is a combination of strength of selection [effect size] and the proportion of the tree affected. A subset of branches can be selected for testing as well, in which case an additional (nuisance) parameter will be inferred -- the non-synonymous rate on branches NOT selected for testing.

Input

1. A FASTA sequence alignment.
2. A phylogenetic tree in the Newick format

Note: the names of sequences in the alignment must match the names of the sequences in the tree.

Output

A JSON file with analysis results (http://hyphy.org/resources/json-fields.pdf).

A custom visualization module for viewing these results is available (see http://vision.hyphy.org/MEME for an example)

Further reading

http://hyphy.org/methods/selection-methods/#MEME

Tool options

--code              Which genetic code to use

--branches          Which branches should be tested for selection?
                        All [default] : test all branches

                        Internal : test only internal branches (suitable for
                        intra-host pathogen evolution for example, where terminal branches
                        may contain polymorphism data)

                        Leaves: test only terminal (leaf) branches

                        Unlabeled: if the Newick string is labeled using the {} notation,
                        test only branches without explicit labels
                        (see http://hyphy.org/tutorials/phylotree/)

 --pvalue           The significance level used to determine significance