1. DNA computing on surfaces
Qinghua Liu et al. University of Wisconsin
Nature 2000
Presented by Jung, Hyun joon
SNU CSE
DCSLAB
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Contents
Introduction
Surface-based approach to DNA Computation
Satisfiability Problem (SAT)
SAT Computation with Surface-based approach
DNA Computation Simulation
Conclusion
References
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Introduction
DNA Computing : proposed as a means of solving a class of intractable computational problems
The principle of the techniques has been demonstrated experimentally
Hamiltonian path problem
Problem exist with scale-up of the test tube-based approach for a number of reason
Poor efficiencies of the purification and separation steps
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In this paper
As a alternative technology
DNA strands are immobilized on a surface
The solution set of oligos is initially attached to a surface
Surface : glass, silicon, gold or beads
Operation : hybridization from solution, exonuclease degradation to extract the desired solution
Many advantage for robust DNA computation
Reduce losses of DNA molecules during purification steps
Recognized by Adleman’s use of magnetic support particles
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5. Surface-based Approach to DNA Computing (1/3)
Make : synthesized
Attach : immobilized in an unaddressed fashion
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6. Surface-based Approach to DNA Computing (2/3)
3. Mark : by hybridizing to the surface those oligonucleotides that are complementary to the strands which do satisfy the clause
4. Destroy : destruction of single strands via Exonuclease I
5. Unmark : by washing the surface in distilled water
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7. Surface-based Approach to DNA Computing (3/3)
6. Readout : Polymerase Chain reaction amplification and hybridization to an addressed array
Polymerase Chain Reaction
a common method of creating copies of specific fragments of DNA. PCR rapidly amplifies a single DNA molecule into many billions of molecules.
In one application of the technology, small samples of DNA, such as those found in a strand of hair at a crime scene, can produce sufficient copies to carry out forensic tests.
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8. Satisfiability Problem (1/2)
The SAT problem is an NP-complete problem in boolean logic.
Composed of n clause
Clause is composed of each variables which may be true or false
Should satisfy each clause
Should satisfy statements
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9. Satisfiability Problem (2/2)
All method for solving the SAT Problem with modern computer require a number of steps that grows exponentially with the number of variables.
General algorithm require for large n
Optimized algorithm also require for large n
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10. SAT Computation with Surface-based approach (1/7)
DNA sequence and encoding scheme
sequence serves as a ‘spacer’ group to separate the hybridizing sequence from the support
GCTT and TTCG sequences are the “word label” used to target hybridization to a particular word
sequence is used to encode information
5’-HS GCTTvvvvvvvvTTCG-3’
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11. SAT Computation with Surface-based approach (2/7)
16 sequences to solution candidate
S0(0000)
S1(0001)
S2(0010)
S3(0011)
S4(0100)
S5(0101)
S6(0110)
S7(0111)
S8(1000)
S9(1001)
S10(1010)
S11(1011)
S12(1100)
S13(1101)
S14(1110)
S15(1111)
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12. SAT Computation with Surface-based approach (3/7)
Cycle 1 – clause 1
S0(0000), S1(0001) are destroyed
0 V 0 V 0 = 0 hence, they cannot satisfy in clause 1
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13. SAT Computation with Surface-based approach (4/7)
Cycle 2 – clause 2
S2(0010), S6(0110) are destroyed
hence, they cannot satisfy in clause 2
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14. SAT Computation with Surface-based approach (5/7)
Cycle 3 – clause 3
S4(0100), S5(0101),S12(1100),S13(1101) are destroyed
hence, they cannot satisfy in clause 3
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15. SAT Computation with Surface-based approach (6/7)
Cycle 4 – clause 4
S10(1010), S11(1011),S14(1110),S15(1111) are destroyed
hence, they cannot satisfy in clause 4
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16. SAT Computation with Surface-based approach (7/7)
solution Sx
Encoding number c1 c2 c3 c4
All S3
0011
0V0V1
1V1
1V0 1 S7
0111
0V1V1
0V1 S8
1000
1V0V0
1V1V0 S9
1001
1V1V1
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Read-out Step
The signal intensities for the spots corresponding to the correct solutions : 10 times to 777 times greater
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Shortcomings
Each steps in the previous-described DNA computing process is chemically complex and subject to error
Ex) mark operation :
Due to the nature of chemical reaction kinetics
the hybridization-driven formation of duplex structures on the surface will be incomplete
unwanted destruction during the “destroy” step
The destruction of single-stranded DNA molecules on the surface by E. coil exonuclease I is not perfect
Approximately 94% of unmarked single-stranded immobilized DNA molecules can be removed
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19. DNA Computation Simulation (1/4)2 3 4 5 6 7 8 9 10 11 12 13 14 15 2 3 4 5 6 7 8 9 10 11 12 13 14 15 2 3 4 5 6 7 8 9 10 11 12 13 14 15 8 9 10 11 12 13 14 15 4 5 6 7 12 13 14 15 2 3 6 7 10 11 14 15
Step1
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20. DNA Computation Simulation (2/4)3 4 5 6 7 8 9 10 11 12 13 14 15 3 4 5 7 8 9 10 11 12 13 14 15 3 4 5 7 8 9 10 11 12 13 14 15 7 8 9 10 11 12 13 14 15 4 5 8 9 12 13 3 5 7 9 11 13 15
Step2
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21. DNA Computation Simulation (3/4)7 8 9 10 11 14 15 3 7 8 9 10 11 14 15 3 4 5 7 8 9 10 11 12 13 14 15 3 8 9 10 11 3 7 10 11 14 15
Step3
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22. DNA Computation Simulation (4/4)
Solution 3 7 8 9 3 7 8 9 10 11 14 15 3 7 8 9 3 7 8 9
Step4
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Conclusion
DNA computing on a surface
Mark, destroy, unmark operation
Readout by PCR
Scaling up to problems with more variables
Reduce losses of DNA molecules compare to previous methodology
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References
Adleman, L. M. Molecular computation of solutions to combinatorial problems. Science 266, (1994)
Smith, L. M. et al. A surface-based approach to DNA computation. J. Comput. Biol. 5, (1998)
Frutos, A. G. et al. Demonstration of a word design strategy for DNA computing on surfaces. Nucl. Acid. Res. 25, (1997)
Guo, Z., Guilfoyle, R. A., Thiel, A. J., Wang, R. & Smith, L. M. Direct fluorescence analysis of genetic polymorphisms by hybridization with oligonucleotide arrays on glass supports. Nucl. Acid. Res. 22, (1994)
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References
Lipton, R. J. DNA solution of hard computational problems. Science 268, 542±545 (1995).
Frutos, A. G., Smith, L. M. & Corn, R. M. Enzymatic ligation reactions of DNA ``words'' on surfaces for DNA computing. J. Am. Chem. Soc. 120, 10277±10282 (1998).
Haoyang W. An improved surface-based method for DNA computation. Elsevier. BioSystems 59, 1± 5 (2001).
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