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Optimizer for degenerate codon use in phage library generation

Project description

Phagetrix

Open in Google Colab DOI PyPI version Action Status

A codon optimizer for phage display library generation.

When making phage display libraries, it's easy to run out of permutations. 1 liter of phage solution can hold about $10^{12}$ different sequences.

We can approximate how many combinations we generate with $(nr\ of\ choices)^{(nr\ of\ positions)}$. If we change the aminoacids to "any" aminoacid, we can change about 9 AA's: $20^9 \approx 10^{12}$ permutations.

If we use the degenerate codon capabilities of the manufactureres such as IDT to the fullest, we can probably make combinations that are partially rational, and allow for 6 permutations in any postion.

That allows us to check out many more combinations that are likely to work: $6^{15} \approx 10^{12}$, so about 15 variable AA's instead of 9.

This tool allows you to easily specify what AA permutations you want, in which position, and calculates the best sequence of degenerate codons.

Example

PhageTrix is a tool to generate phage display libraries. You probably have an idea what AA's you want to replace, and what you want to replace them with. The sequence companies have a reasonable number of The file format has the AA sequence on the first line. Each following line is the AA to be changed, the digits indicating its position, and the AA options that should be generated for that position. The AA options are concatenated together with no spaces. Phagetrix will generate the best degenerate codon for each position.

Example:

VLPYMVAQVQ
P3PFYA
Y4YPFYE
A7AVILM
  1. The first line is the sequence you want to alter.
  2. The P in position 3 should be either a P, F, Y or an A
  3. The Y in position 4 should be either a Y, P, F, or an E
  4. The A in position 7 should be either an A, V, I, L or an M

Output:

   1   2   3   4   5   6   7   8   9  10
   V   L   P   Y   M   V   A   Q   V   Q
 GTT CTT BHC BHW ATG GTT DYR CAG GTT CAG

GTTCTTBHCBHWATGGTTDYRCAGGTTCAG

By default this uses the degenerate codons from IDT.

Try it

  • Open in Google Colab
  • Install it on your machine pip install phagetrix to get the phagetrix command line tool. Requires python3.

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