mRNA Sequence Design Using Optimization Techniques

_{Science Fair 2020-2021}

Current methods:

• Codon mapping - Mapping the codon values to a lookup table. Simple, quick, and high nucleotide and codon % matches.
• Discrete optimization version 0:
  • Iterates through and for each codon finds the best optimized codon.
  • Problems with high GC content at beginning and cutting down at end.
  • Slow, relatively good results but not state-of-the-art.
• Discrete optimization version 1:
  • Iterates through, measures fitness within a specific frame(size 12), and for each codon finds best optimized codon.
  • GC content can get extremely close(within 0.1%) to actual vaccine, at cost of major nucleotide and codon differences.
  • Fixes GC problems slightly(although sometimes avg GC content within a specific area might dip, this fixes it so it's not indicative of real vaccine)
• Discrete optimization version 2:
  • Iterates through, measures fitness for entire sequence and finds best codon to change.
  • Very good results - High nucleotide and codon % matches
  • Also high GC % and codon frequency %
  • Much slower than versions 0 and 1
• Discrete optimization version 3:
  • Same as version 2, but optimizes fitness function
  • Converges slightly faster
  • Fitness function normalized and doesn't require alpha value(which is a constant that isn't guaranteed to be the same across different viruses)

SCHEDULE

Big Dates

Feb. 7: Scienteer finished

Feb. 13: Slides finished

Feb. 15: Hear from judges

Feb. 20: Presentation

Todo

• Find the antigen
  • Given antigen name, isolate it within full genome and run program on it
  • Create lookup table and identify which to use
• Create GA measuring:
  • GC content
  • Codon optimization(looking at frequency of codons in human body & use less rare ones)
  • Hairpin structures
  • CAI Index
• Fix collapsed

Scienteer Info

• [x] Title and category
• [x] Team status
• [x] Project start date
• [x] Survey questions
• [x] Research Plan
• [x] Extra Forms
• [x] Bibliography
• [x] Research Locations
• [x] External Signatures
• [x] Project Approval Method
• [x] Teacher Approval
• [x] IRB Approval
• [x] SRC Approval
• [x] Project end date
• [x] 1C Signature
• [x] SRC Post-approval
• [ ] Project Summary
• [ ] Abstract

Parts

• [ ] Background
• [x] Rationale
• [ ] Introduction
• [ ] Purpose
• [x] Hypothesis
• [ ] Code
• [x] Procedure
• [x] Materials
• [ ] Conclusion
  • [ ] Problems Encountered
  • [ ] Future Expansions
  • [ ] Practical Applications
• [ ] Bibliography

Day-by-Day

Feb. 1

• [x] Research plan
• [x] Extra forms
• [x] Implement CAI index
• [x] Background
• [x] Rationale
• [x] Create vaccine given specific features(codon_mapping.py + identify_antigen.py)

Feb. 2

• [x] Materials
• [x] Implement CAI index

Feb. 3

• [x] Procedure
• [x] GA - Implement mutation, population selection

Feb. 4

• [ ] Problems Encountered
• [ ] Create simple shell script to execute
• [ ] Implement self-replicating vaccine
• [ ] Bibliography
• [ ] Introduction
• [ ] Purpose
• [ ] Background

Feb. 5

• [ ] Future Expansions
• [ ] Practical Applications
• [ ] Implement self-replicating vaccine
• [ ] Apply GA to 3 viruses

Feb. 6

• [ ] Connect self-replicating vaccine to lookup table, find corresponding structural proteins
• [ ] Apply to 3 viruses
• [ ] Calculate when to finish
• [ ] Rendering:
  • [ ] Antigen shading
  • [ ] Run vaccine through AlphaFold + render w/ GFuzz
• [ ] Select best 5' and 3' UTRs + cap
• [ ] Conclusion

Feb. 7

• [ ] Annotate code!
• [ ] Major clean-up of files
• [ ] Continue rendering
• [ ] Conclusion
• [ ] Optimize

Feb. 8

• [ ] Presentation work
• [ ] Continue rendering work
• [ ] Slides
• [ ] Self-replication work

Feb. 9

• [ ] Rendering
• [ ] Presentation
• [ ] Slides
• [ ] Self-replication work

Feb. 10

• [ ] Rendering
• [ ] Apply GA to more viruses
• [ ] Optimize GA if possible
• [ ] Creating UI

Feb. 11

• [ ] Optimize GA
• [ ] Apply GA to more viruses
• [ ] Self-replication work
• [ ] Slides
• [ ] Creating UI

Feb. 11

• [ ] Filler - [ ] Add more info to binder
• [ ] Slides
• [ ] Creating UI

Feb. 12

• [ ] Putting down final results
• [ ] Finalizing slides