AQUEOUS COMPUTING - Writing on Molecules -

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AQUEOUS COMPUTING - Writing on Molecules -

• T. Head, M. Yamamura, and S. Gal
• Binghamton University

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1. Introduction

• The only way to compute with DNA?
• 1 design sequences for DNA molecules
• 2 order many custom DNA molecules
• 3 anneal and filter
• ( 4 if failure goto 1 )

• ?
• Aqueous computing
• framework for using molecular memory
• laboratory implementation

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Molecular Memory

• Memory LSI HD
• Address wired grid head pos.
• Content electronic magnet ic
• 1. molded together
• 2. fixed on solid materials
• 3. serial processing

AQUEOUS
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2. Mathematical Basis

• Common algorithmic problem (CAP)
• a description of the pattern of the problem
• Aqueous algorithm
• a way to use molecular memory

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Common algorithmic problem

• CAP
• given S finite set
• F ?2S (the forbidden subsets)
• find the largest cardinal number n for which
  there is a subset T of S for which Tn,
  ?U?F U?T.

• NP-complete problems having the CAP pattern
• maximum independent set
• minimum vertex cover
• Hamiltonian cycles
• Boolean satisfiability, etc.

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Example

• Maximum independent set problem
• given G(V, A) (the arcs are forbidden)
• find max T s.t. T?V ,?x,y?T, x,y?A

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Aqueous Algorithm

• Initialize
• For each s1, s2, ..., sk in F Do
• Pour (k)
• 1 SetToZero( s1 )
• 2 SetToZero( s2 )
• ...
• k SetToZero( sk )
• Unite
• EndFor
• MaxCountOfOnes

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Example
Initialize 111
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3. Biomolecular Implementation

• DNA modification enzymes
• how to write on molecules
• DNA plasmid
• use of bacteria and blue/white selection

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Write on molecules

• Restriction enzyme
• cuts DNA at a specific subsequence (site)
• 5-TATCGA-3
• 3-ATAGCT-5
• ? Hind III
• 5-T ATCGA-3
• 3-ATAGC T-5
• Circular DNA modification enzymes
• Bit 1 (site exists), 0 (no site)

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Cut/fill/paste

• 5-TATCGA-3 Bit1, circular
• 3-ATAGCT-5
• cut ? restriction enzyme
• 5-T ATCGA-3 linear
• 3-ATAGC T-5
• fill ? DNA polymerase
• 5-TATCG ATCGA-3
• 3-ATAGC TAGCT-5
• paste ? DNA ligase
• 5-TATCGATCGA-3
• 3-ATAGCTAGCT-5 Bit0, circular

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Cloning with DNA plasmid

• DNA plasmid
• circular, double stranded
• set of unique sites
• multiple cloning site (MCS)
• transform to bacteria
• useful genes
• antibiotics resistance (ex.ampr)
• coloring matters (b-galactosidase)

NotI XbaI SpeI BamHI XmaI PstI EcoRI
EcoRV HindIII ... 5-GCGGCCGCTCTAGAACTAGTGGATCCCCC
GGGCTGCAGGAATTCGATATCAAGCTTATCGAT-3 3-CGCCGGCGAC
ATCTTGATCACCTAGGGGGCCCGACGTCCTTAAGCTATAGTTCGAATAGC
TA-5
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Genetic code translation

• Genetic code
• translated into a series of amino acids by groups
  of 3 base pairs (codon)
• Reading frame
• 3 different meanings
• ex) 5-GCTCTAGAACTAGTGGATCCCCCGGGCTGCAGGAATTCGA
  TATC
• A L E L V D P P G C R N S I
• . . . . . . . . . . . . . .
• . . . . . . . . . . . . . .
• (under construction)

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Blue / white selection

• initial DNA plasmid
• express b-galactosidase gene ? blue

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Blue/white example
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Preliminary results

• XbaI BamHI
  HindIII
• pBSK GCTCTAGAACTAGTGGATCCCCCGGGCTGCAGGAATTCGATATC
  AAGCTTATCGATACCGTCG
• A L E L V D P P G C R N S I S
  S L S I P S
• H GCTCTAGAACTAGTGGATCCCCCGGGCTGCAGGAATTCGATATC
  AAGCTAGCTTATCGATACC
• A L E L V D P P G C R N S I
  S S stop
• HB GCTCTAGAACTAGTGGATCGATCCCCCGGGCTGCAGGAATTCGA
  TATCAAGCTAGCTTATCGA
• A L E L V D R S P G L Q E F
  D I K L A Y R
• HBX GCTCTAGCTAGAACTAGTGGATCGATCCCCCGGGCTGCAGGAAT
  TCGATATCAAGCTAGCTTA
• A L A R T S G S I P R A A G I
  R Y Q A S L

sample blue / white accuracy H 4 /
40 87 HB 3 / 80 96 HBX 97 /
17 85
SetToZero Hind III -gt BamH I -gt Xba I
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Example
under construction
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4. Discussion

• Advantages as DNA computing
• start with one DNA plasmid
• no custom DNA for individual problem
• amplify in bacteria
• blue/white selection as debugging tool
• preserving the distribution of DNA plasmids

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5. Conclusion

• Molecular Memory
• Aqueous Algorithm
• general framework to use molecular memory
• Cut/fill/paste
• laboratory implementation
• Further issues
• scale up speed up
• new algorithm fits bacteria

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International Connection
Binghamton University (USA)
Aqueous Computing
Leiden University (Netherlands)
Tokyo Institute of Technology (Japan)
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Acknowledgement

• Xia Chen Shalini Aggarwal in S.Gal Laboratory
  at Binghamton University
• NSF CCR-9509831
• DARPA/NSF CCR-9725021
• JSPS-RFTF 96100101
• LCNC at Leiden University