RNA-Undesign

Algorithms for Identifying the Undesignability of RNA secondary structures

Introduction

This project explores the undesignability of RNA secondary structures, under the context of RNA design, building upon the research presented in the paper by T. Zhou et al. [1][2].

References

[1] Zhou, T., Tang, W.Y., Mathews, D.H. and Huang, L. "Undesignable RNA Structure Identification via Rival Structure Generation and Structure Decomposition." (RECOMB 2024, arXiv preprint)
[2] Zhou, T., Tang, W.Y., Apoorv, M., Mathews, D.H. and Huang, L. "Scalable and Interpretable Identification of Minimal Undesignable RNA Structure Motifs with Rotational Invariance" (under review)

Datasets

Eterna100
ArchiveII
Motifs of length up to 14 (excluding motifs with external loops for comparison with CountingDesign):

• Designable motifs of length up to 14
• Undesignable motifs of length up to 14

Results

Detailed results for undesignable motifs of length up to 14:

• All motifs (4561)
• Unique motifs (1805) by rotational invariance

Dependencies

• GCC 4.8.5 or above

Build

Linux

# Test with CentOS
$ make main   
$ make main_nosh  # turn off special hairpins

Mac

# Test with Apple Silicon
$ make main_mac   
$ make main_nosh_mac  # turn off special hairpins

Rival Motifs

---

Rotation Invariance

Environment Variables

$export OMP_NUM_THREADS=8 # parallel computing eabled by OpenMP
$export PATH_UNDESIGNABLE_LIB=path/to/lib_undesignable.txt
$export PATH_DESIGNABLE_LIB/path/to/motifs/libs/lib_designable.txt

FastMotif

$echo ".((......((......))......((......((......))......((......))......))......))....." | ./bin/main --alg fastmotif

Rival Motifs Search

echo "(.(*)...(..(*)))" | ./bin/main --alg motif # motif as a dot-bracket string where (*) is a boundary pair

RIGEND

Undesignability Alg1

$./bin/main --alg 1
......(.........((((.....)))).........)......................
................((((.....))))................................

Undesignability Alg2

$./bin/main --alg 2
AAAAUGAGCCCCACGAAAGGAGAGUGCUCACAAA
....((((((((.(....)).).).)))))....
....(((((((..(....)..).).)))))....

Undesignability Alg2 (constrained)

$./bin/main --alg 2c
UUAAGGGAAAAUCUUAGCCGAGAAAUCGGAUCCAAAGCGGCAUAAAAAAGAAAGCGCCGAAAUUCGCAGAAAUGCGAGAAAGGCAAGCAAAGAAUUCGGCAGAAAAAAUGCCGACCGGGCAAUGAAAAUUCGCCCGUGGAGCCAAGCGGG
((((((.....)))))(((((....)))).)((...(((((............(((((....((((((....))))))...)))..)).......((((((.......))))))(((((((((....))).))))).)..)))..)))))
((((((.....))))).((((....))))..((...(((((............(((((....((((((....))))))...)))..)).......((((((.......))))))(((((((((....))).))))).)..)))..)))))

Undesignability Alg3

$./bin/main --alg 3
ACUAAAUGGUGAGCAGACCCAGUGGAAACACACGCAGCCGAAAGGUACCCAUCCGAGAGGAAGUCAGGCGAAAGCUAACGGAAAGAACGUAGACAGGGAGCGAGGGACAAAGACUGCAAGGGAAAGUACACAAGACAAAGUAAAAAAAGGUGAGGCAGGGGAAACCCCGGGAAACCGGUCGAAAGACGCCAGCAAACCGCAGAAACAGCCACCCAGCGAGACAGACAAAAGCGGAUACGUAGUCGACGGAAACGUAGUCAGGGGAAACCCACGCAAUCGAAAGAUAGGGAGUCGGUGAAAACCAGAGAAAUCUACUCAAAAGAGGACAGGCAGCGGAACCCCUACACCGAAAAAA
.......((((.((((.(((.(((....))).(((.(((....))).(((.(((....))).(((.(((....))).(((.......))).))).))).))).))).(...).)))).((((...((.(((...((...))........))).(((.(((....)))(((....)))(((....)))))).))...((((.(...).(((.(((.(((.(((.(((....(((....))).))).(((....))).))).(((....))).))).(((....))).))).((((((....)))(((....))).(((....)))))).))).))))...)))).)))).......

Utilities

Energy Evaluation

$./bin/main --alg eval
CACACGCACUACAAAAUGUCCAAAGGAAAAGGCACCACCAGCAAAGCACCAAAGGUAAGGGGAAAAG
.....((.((.((...)).((...))...)))).((.((.((...)).((...))...)))).....
(output)total energy: -3.00

Differential positions

$./bin/main --alg dp
..((((((((.......(.((((((....)))))).(((((((....))))))).).......))))))))..
..((((((((.........((((((....)))))).(((((((....))))))).........))))))))..

Energy difference

$./bin/main --alg ed
GGGAGACCCAAAAAAAAGGGCAACUGCAAAAAGGAGACAGCACCCCGAAAAAAGACUGGAAAAAGGGCGAAAAGCUCGAAAAACACGACCAACGGAAAACAGGACGAAAGAGAACAAGCAAGCCAAAGGGAAACAGACUAAAAACGCGAAAGCGACUGCAAAGGGGGAGAAAAAGCGACCCUGAACGAAAAAGGGGCGAAAAAUUGGAACAAAAAAAGGAGGGGGGAAAGGAAAGUCAAAGACACUCGAAACGAGUGAGCGGGCAAAAAAAAAAACGGGGGAUGAAUAACGGACGGAAACGCGGCGGAAAGCGAAAAAAAGAAAAACGUCGUACGGACUACUGGGGUGCAAAAAAAAGGAGGGGCGCAAAAAGGAAAAAACAGGGUCCACUA
((..(((((........(.((..((.(.....(....).((((((((.........((......((((.....))))......))...((..((.......(..(......)..)..((..((.....(....).((((.....(((.....(..((.(...).))..).....))).((((...(.......(..(.((...)).)..).......)...))))........)))).....((((((...)))))).))..))...........))..)).........(..((....)((((((.....(........).....))))))..)..)...))))))))........).))..)).).....(.......).)))))..)).
((..(((((........(.((..((.(.....(....).((((((((.........((......((((.....))))......))...((..((.......(..(......)..)..((..((............((((.....(((.....(..((.(...).))..).....))).((((...(.......(..(.((...)).)..).......)...))))........)))).....((((((...)))))).))..))...........))..)).........(..((.....((((((.....(........).....)))))).))..)...))))))))........).))..)).).....(.......).)))))..)).
ref1 energy: -68.20
ref2 energy: -72.70
GGGAGACCCAAAAAAAAGGGCAACUGCAAAAAGGAGACAGCACCCCGAAAAAAGACUGGAAAAAGGGCGAAAAGCUCGAAAAACACGACCAACGGAAAACAGGACGAAAGAGAACAAGCAAGCCAAAGGGAAACAGACUAAAAACGCGAAAGCGACUGCAAAGGGGGAGAAAAAGCGACCCUGAACGAAAAAGGGGCGAAAAAUUGGAACAAAAAAAGGAGGGGGGAAAGGAAAGUCAAAGACACUCGAAACGAGUGAGCGGGCAAAAAAAAAAACGGGGGAUGAAUAACGGACGGAAACGCGGCGGAAAGCGAAAAAAAGAAAAACGUCGUACGGACUACUGGGGUGCAAAAAAAAGGAGGGGCGCAAAAAGGAAAAAACAGGGUCCACUA
ref1 energy = 7.20, ref2 energy = 2.70
pass test: true
e1 - e2: 4.50
delta  : 4.50

or

$./bin/main test_diff  < data/seq_refs.txt # batched input