DNA computing on surfaces Qinghua Liu et al. University of Wisconsin Nature 2000 Presented by Jung, Hyun joon SNU CSE DCSLAB 2019-02-19 Advanced Artificial Intelligence

Advanced Artificial Intelligence Contents Introduction Surface-based approach to DNA Computation Satisfiability Problem (SAT) SAT Computation with Surface-based approach DNA Computation Simulation Conclusion References 2019-02-19 Advanced Artificial Intelligence

Advanced Artificial Intelligence 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 2019-02-19 Advanced Artificial Intelligence

Advanced Artificial Intelligence 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 2019-02-19 Advanced Artificial Intelligence

Surface-based Approach to DNA Computing (1/3) Make : synthesized Attach : immobilized in an unaddressed fashion 2019-02-19 Advanced Artificial Intelligence

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 2019-02-19 Advanced Artificial Intelligence

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. 2019-02-19 Advanced Artificial Intelligence

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 2019-02-19 Advanced Artificial Intelligence

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 2019-02-19 Advanced Artificial Intelligence

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’ 2019-02-19 Advanced Artificial Intelligence

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) 2019-02-19 Advanced Artificial Intelligence

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 2019-02-19 Advanced Artificial Intelligence

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 2019-02-19 Advanced Artificial Intelligence

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 2019-02-19 Advanced Artificial Intelligence

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 2019-02-19 Advanced Artificial Intelligence

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 2019-02-19 Advanced Artificial Intelligence

Advanced Artificial Intelligence Read-out Step The signal intensities for the spots corresponding to the correct solutions : 10 times to 777 times greater 2019-02-19 Advanced Artificial Intelligence

Advanced Artificial Intelligence 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 2019-02-19 Advanced Artificial Intelligence

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 2019-02-19 Advanced Artificial Intelligence

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 2019-02-19 Advanced Artificial Intelligence

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 2019-02-19 Advanced Artificial Intelligence

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 2019-02-19 Advanced Artificial Intelligence

Advanced Artificial Intelligence 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 2019-02-19 Advanced Artificial Intelligence

Advanced Artificial Intelligence References Adleman, L. M. Molecular computation of solutions to combinatorial problems. Science 266, 1021-1024 (1994) Smith, L. M. et al. A surface-based approach to DNA computation. J. Comput. Biol. 5, 255-267 (1998) Frutos, A. G. et al. Demonstration of a word design strategy for DNA computing on surfaces. Nucl. Acid. Res. 25, 4748-4757 (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, 5456-5465 (1994) 2019-02-19 Advanced Artificial Intelligence

Advanced Artificial Intelligence 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). 2019-02-19 Advanced Artificial Intelligence