# User:R. Eric Collins/MBL/ML

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< User:R. Eric Collins | MBL

Maximum Likelihood

## Large ML inference

- GARLI
- branch length optimization makes up majority of ML inference time because changing one branch affects lengths of every other branch.
- this problem gets untenable with large trees (e.g. >50 taxa)

- how accurate does a tree likelihood need to be?
- evolutionary (not technically genetic) algorithm
- start with a large number of individuals (parameter sets)
- compete them against each other, unfit ones die out (and some fit ones, but never best fit)
- can give starting tree that you believe, even if it has polytomies

- difficulty due to parameter estimation: nucleotide < amino acid < codon (because of transition probability estimation)

- when to use codons
- mixture of divergent and closely related sequences

- not always better, plus it takes longer

- when the models get better

Questions:

- which branches take longest to calculate? leaves? deep branches?
- settings contstraints... are there any algorithms that 'fill in' the valleys (level the mountains)
- when do you need a tree this good? use cases for depth-of-tree'ing would be useful
- ancestral state reconstruction... indel/gap models