# DNA Computing on Surfaces by bxk16778

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```									DNA Computing on Surfaces

Anne Condon, Computer Science, UBC
Robert Corn, Chemistry, U. Wisconsin
Max Lagally, Materials Science, U. Wisconsin
Lloyd Smith, Chemistry, U. Wisconsin
Goals

• Encode information in DNA strands

• Compute on many strands in parallel:
chemical manipulations = logical
operations
“…the number of of operations per second …
would exceed that of current supercomputers
by a thousandfold…remarkable energy
efficiency… information density a dramatic
improvement over existing storage media

“for certain intrinsically complex problems…where
existing electronic computers are very inefficient and
where massively parallel searches can be organized to
take advantage of the operations that molecular biology
currently provides, molecular computation might
compete with electronic computation in the near term”
Outline
Background
• What is computation? What is DNA?
• DNA computation
• in the biotech industry
• in the solution of combinatorial problems
•Research on DNA computation

DNA Computing on Surfaces
•Models
•Experiments

Conclusions
What is Computation?
(very simple view)
• Input: string over finite alphabet
• Process: determine if input satisfies
some property
• Output: yes or no
Satisfy a Property: Binary Inputs
Output: 1
• set the output of                        and
a circuit to 1                       1
or
0          1
and         not

Input:   1    0           0         1
Satisfy a Property:
Non-binary Inputs
Output: C
• Set the output of a
generalized circuit to            G
a given value
T    G

A   G     C     G
Simple Parallel Computation

• Input: set of strings
• Process: independently for each input,
determine if it satisfies a
common circuit
• Output: indicate whether there exists an
input satisfying the circuit
What is DNA?
“DNA Computation:” Affymetrix Arrays
• Input: strings over {A,C,G,T},
(represented as the corresponding
single-stranded DNA)
Photolithography used to synthesize
and array DNA strands on a planar
surface
“DNA Computation:” Affymetrix Arrays

• Process: e.g. for each input, test if it
approximately matches a given string
(i.e. hybridizes to Watson-Crick complement
of given string)
“DNA Computation:”
Affymetrix Arrays

• Output: fluorescence detection
Experiment
S
• Input: generate random paths
• Process:                                 2       1

3
• select paths from S to T
• select paths with 7 nodes                5

• select paths entering all    4
nodes at least once
T
• Output: “yes” iff path remains
Generate Random Paths

• Associate DNA strands with nodes and edges

2           3           4           5

• Join edge strands in test tube to form double-
stranded “paths” (hybridization, ligation)

• Wash to form single-stranded paths
Select Paths That Enter Node 2
• Attach strand associated with node 2 to
beads and introduce to test tube
• The paths that enter node 2 hybridize to
• Remove beads; wash and detach desired
paths
Biomolecular Computation Research

• “Classical” DNA/RNA computation
(e.g. search-and-prune)
• O(1)-biostep computation
(e.g. self-assembly of 3-D DNA molecules)
Biomolecular Computation
Research
• Splicing-based computation
• Non-computational applications
(e.g. exquisite detection, DNA2DNA computation,
DNA nanotechnology, DNA tags)
DNA Computing on Surfaces
DNA Computing on Surfaces
• Advantages over “solution phase” chemistry:
•Facile purification steps
•Reduced interference between strands
•Easily automated
•Loss of information density (2D)
•Lower surface hybridization efficiency
•Slower surface enzyme kinetics
DNA Surface Model: Input
DNA strands representing the set {0,1}^n are
synthesized and subsequently immobilized on a
Encoding of Binary Information
in DNA Strands
Word Bit
1
2    A strand is comprised of
1        3
4
1
words. Each word is a
2
2        3
4
short DNA strand (16mer)
A
C
.
.    representing one or more
3    C   .
T
.
.
bits.
.
4
DNA Word Design Problem
• Requirements of a “DNA code”:
– Success in specific hybridization between a DNA
code word and its Watson-crick complement
– Few false positive signals
• Virtually all designs enforce combinatorial
constraints on the code words
• Applications:
– Information storage, retrieval for DNA computing
– Molecular bar codes for chemical libraries
What combinatorial constraints
are placed on DNA Codes?
• Hamming: distance between two code
words should be large
• Reverse complement: distance between a
word and the reverse complement of
another word should be large
• Also: frame shift, distinct sub-words,
forbidden sub-words, …
Work on DNA code design
• Seeman (1990): de novo design of
sequences for nucleic acid structural
engineering
• Brenner (1997): sorting polynucleotides
using DNA tags
• Shoemaker et al. (1996): analysis of
yeast deletion mutants using a parallel
molecular bar-coding strategy
• Many other examples in DNA computing
Word Design Example
DNA Surface Model: Process
•MARK strands in which bit j = 0 (or 1):
hybridize with Watson-Crick complements of word
containing bit j, followed by polymerization
•DESTROY
•UNMARK
DNA Surface Model: Process

•MARK strands in which bit j = 0 (or 1)
•DESTROY unmarked strands:
•UNMARK
DNA Surface Model: Process
MARK strands in which bit j = 0 (or 1):
hybridize with Watson-Crick complements of word
containing bit j, followed by polymerization
DNA Surface Model: Process
•MARK strands in which bit j = 0 (or 1)
•DESTROY unmarked strands
•UNMARK strands:
wash in distilled water
DNA Surface Model: Output

• Detect remaining strands (if any)
by detaching strands from surface and
amplifying using PCR (polymerase chain
reaction).
Computational Power of
DNA Surface Model
Theorem: Any CNFSAT formula of size m
can be computed using O(m) mark, unmark
and destroy operations.

Theorem: Any circuit of size m can be
computed using O(m) mark, unmark,
destroy, and append operations.
Surface DNA Computation:
the Satisfiability Problem
•Input: 16 strands
•Process: MARK if bit z = 1                      and
MARK if bit w = 1
MARK if bit y = 0
DESTROY                   or       or           or   or
UNMARK

MARK if bit w = 0
not         not       not
MARK if bit y = 0
DESTROY
UNMARK                z        w            y        x

…
•Output: exactly those strands that satisfy
the circuit remain on the surface.
DNA Computing on Surfaces:
Experiments

Students: Tony Frutos, Susan Gillmor,
Zhen Guo, Qinghua Liu,
Andy Thiel, Liman Wang
MARK Operation: 4-Base Mismatch Word Design
Repeated MARK, DESTROY, UNMARK Operations
Append (DNA Ligase)

A. Hybridize with Cb
B. Hybridize with Cab, Wb
C. Ligate; Wash;
Hybridize with Cb.
Two-Word Mark and Destroy
A. Mark C1a, C1b, C2b
B. Ligate; Melt single words
C. Destroy; Unmark; Mark C1a, C1b, C2b.
Surface Attachment Chemistry

•PCR amplify words
remaining on surface

•Detect PCR products on
4-Variable SAT Demo
•Synthesize; Attach
•Mark
•Destroy     Cycle
•Umark
Conclusions
• DNA computing has expanded the notion of what
is computation
• Solid-phase chemistry is a promising approach to
DNA computing
• DNA computing will require greatly improved
DNA surface attachment chemistries and control
of chemical and enzymatic processes
• New research problems in combinatorics,
complexity theory and algorithms
Open Problem:
DNA Strand Engineering
Given a DNA strand, there are polynomial-
time algorithms that predict the secondary
structure of the strand.
Inverse Problem: find an
efficient algorithm that,
given a desired secondary
structure, generates a strand
with that structure.

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