DERNA

DERNA is a tool that enables the design of RNA sequences based on protein sequences. DERNA accepts a protein sequence as input and provides a collection of Pareto optimal solutions consisting of RNA sequences that optimize both minimum free energy and codon adaptation index (CAI). Additionally, DERNA can function as a tool for predicting RNA structures and calculating CAI for given RNA sequences.

If you find this tool useful in your research, please cite the following paper:

@article{gu2024derna,
  title={DERNA enables pareto optimal RNA design},
  author={Gu, Xinyu and Qi, Yuanyuan and El-Kebir, Mohammed},
  journal={Journal of Computational Biology},
  volume={31},
  number={3},
  pages={179--196},
  year={2024},
  publisher={Mary Ann Liebert, Inc., publishers 140 Huguenot Street, 3rd Floor New~…},
  doi={10.1089/cmb.2023.0283},
  url={https://doi.org/10.1089/cmb.2023.0283}
}

Installation
- Using conda (recommended)
- Build from source (alternative)
  - Dependencies
  - Compilation
Usage instructions
- Examples

Installation

Using conda

Create a new conda environment named “derna” and install dependencies:
```
conda create -n derna
```
Then activate the created environment: conda activate derna.
Install the package into current environment “derna”:
```
conda install -c bioconda derna
```

Build from source

Dependencies

Recent C++ compiler (C++11)

Compilation

mkdir build
cd build
cmake ..
make

Usage instructions

-i - <input file path>
-o - <output file path>
-m - model <0,1,-1> , 0 for nussinov, 1 for zuker, -1 for eval
-s - mode <1,2,3>, 1 for mfe, 2 for mfe+cai, 3 for sweep
-l - lambda <[0,1]>
-a - sweep increment <(0,1]>
-r - <input rna file path>
-O - <sweep output csv file name>
-g - <[0,inf)>
-t - threshold tau <(0,1)>
-p - threshold tau2 <(0,1)>
-c - <codon usage table file path>
-d - <energy parameters (model) directory>

./derna -i <input> -o <output> -m <model> -s <mode> ...

input: input file path 
output: output file path 
model: integer 0 for Nussinov based model, 1 for Zuker based model, -1 for eval model 
mode: integer 1 for only MFE mode, integer 2 for MFE + CAI mode, integer 3 for lambda swipe mode 
lambda: lambda value for MFE + CAI mode or lambda swipe mode 
incr: increment interval for lambda swipe mode 
swipe: swipe output csv file name 
g: minimal gap allowed in Nussinov based model 
rna: input rna file path for eval model

Examples

Fix $\lambda$

./derna -i ../data/uniprotSeq/P15421.fasta -o P15421_fixed_lambda.txt -m 1 -s 2 -l 0.5

cat P15421_fixed_lambda.txt

protein sequence: MYGKIIFVLLLSGIVSISASSTTGVAMHTSTSSSVTKSYISSQTNGITLINWWAMARVIFEVMLVVVGMIILISYCIR

lambda: 0.5
Zuker CAI
Energy: -74.2202
Time taken by DP is : 32sec
lambda: 0.5,O: -7422.02,mfe: -14870,cai: -25.9662,combined: -7422.02
zuker cai bp: (((((((((.....((((((((((.((((((((.(((((((((...))))))))).)))))))).)))))))))))))))))))((((((....((((((((.(((.((((((((((.(((((((((.(((((.((((((((((((((.((((((((((((....)))))).)))))))))))))))))))).))))))))))))))))))))))))))))))))))))))))),size: 234
zuker rna: AUGUAUGGCXXXXXCAUCUUCGUCUUGCUGCUCUCCGGGAUCGUXUCGAUCUCGGCGAGCAGCACGACGGGGGUGGCCAUGCAUACGAGUXXXXGCAGUAGCXUGAXUAAGAGUUAUXUAUCCUCACXGACCAACGGCAUCACCUUGAXAAAUUGGUGGGCGXXGGCCCGCXUAAUUUUCGAGGUGAUGCUGGUGGUCGUGGGGAUGAUAAUUCUUAUCAGCUACUGCAUUCGU.size: 234
zuker cai rna: AUGUAUGGCAAGAUCAUCUUCGUCUUGCUGCUCUCCGGGAUCGUGUCGAUCUCGGCGAGCAGCACGACGGGGGUGGCCAUGCAUACGAGUACCAGCAGUAGCGUGACUAAGAGUUAUAUAUCCUCACAGACCAACGGCAUCACCUUGAUAAAUUGGUGGGCGAUGGCCCGCGUAAUUUUCGAGGUGAUGCUGGUGGUCGUGGGGAUGAUAAUUCUUAUCAGCUACUGCAUUCGU.size: 234
Codon Adaptation Index: 0.716842
Minimum Free Energy: -148.7

Sweep (default thresholds)

./derna -i ../data/uniprotSeq/P15421.fasta -o P15421_sweep.txt -O P15421_sweep -m 1 -s 3

Estimated time: 10min

Evaluate an RNA sequence

./derna -i ../data/uniprotSeq/P15421.fasta -o P15421_evaluation.txt -r ./data/RNA/P15421_rna.txt -m -1

cat P15421_evaluation.txt

protein sequence: MYGKIIFVLLLSGIVSISASSTTGVAMHTSTSSSVTKSYISSQTNGITLINWWAMARVIFEVMLVVVGMIILISYCIR
eval MFE: -148.7
eval CAI: -28.3932
eval standard CAI: 0.694881

Only consider MFE

./derna -i ../data/uniprotSeq/P15421.fasta -o P15421_MFE_only.txt -m 1 -s 1

cat P15421_MFE_only.txt

protein sequence: MYGKIIFVLLLSGIVSISASSTTGVAMHTSTSSSVTKSYISSQTNGITLINWWAMARVIFEVMLVVVGMIILISYCIR

Zuker
Energy: -148.7
Time taken by DP is : 3sec
Time taken : 3sec
zuker bp:(((((((((.....((((((((((.((((((((.(((((((((...))))))))).)))))))).)))))))))))))))))))((((((....((((((((.(((.((((((((((.(((((((((.(((((.((((((((((((((.((((((((((((....)))))).)))))))))))))))))))).))))))))))))))))))))))))))))))))))))))))), size: 234
zuker rna:AUGUAUGGCXXXXXCAUCUUCGUCCUGCUGCUCUCCGGGAUCGUXUCGAUCUCGGCGAGCAGCACGACGGGGGUGGCCAUGCAUACGAGUXXXXGCAGUAGCXUGAXUAAGAGUUAUXUAUCCUCACXGACCAACGGCAUCACCUUGAXAAAUUGGUGGGCGXXGGCCCGCXUAAUUUUCGAGGUGAUGCUGGUGGUCGUGGGGAUGAUAAUUCUUAUCAGCUACUGCAUUCGU, size: 234
zuker rna:AUGUAUGGCAAAAUCAUCUUCGUCCUGCUGCUCUCCGGGAUCGUUUCGAUCUCGGCGAGCAGCACGACGGGGGUGGCCAUGCAUACGAGUACUAGCAGUAGCGUGACUAAGAGUUAUAUAUCCUCACAGACCAACGGCAUCACCUUGAUAAAUUGGUGGGCGAUGGCCCGCGUAAUUUUCGAGGUGAUGCUGGUGGUCGUGGGGAUGAUAAUUCUUAUCAGCUACUGCAUUCGU, size: 234
zuker cai: 0.694881

Nussinov based model (Fixed $\lambda$ )

./derna -i ../data/uniprotSeq/P15421.fasta -o P15421_nussinov.txt -m 0 -s 2 -l 0.5 -g 1

Specify Codon Usage Table

./derna -i ../data/uniprotSeq/P15421.fasta -o P15421_fixed_lambda.txt -m 1 -s 2 -l 0.5 -c ./data/InputFiles/sample_codon_usage.csv

Specify Energy Parameters

./derna -i ../data/uniprotSeq/P15421.fasta -o P15421_fixed_lambda.txt -m 1 -s 2 -l 0.5 -d ./data/InputFiles/