Granted Patent
B2
US 12,277,999 · App. 16/653,564 · Granted Apr 15, 2025
Re-writable DNA-based digital storage with random access
Inventors:
Olgica Milenkovic (Urbana, IL); S. M. Hossein Tabatabaei Yazdi (Urbana, IL); Yongbo Yuan (Urbana, IL); Jian Ma (Urbana, IL); Huimin Zhao (Champaign, IL)
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Abstract
The disclosure relates to a re-writable DNA-based digital storage system with a random access feature. An example embodiment includes reading a physical nucleotide sequence of 2n+L bases to form a digital representation of the physical nucleotide sequence; dividing the digital representation of the physical nucleotide sequence into an address representation of n bases, followed by a data representation of L bases, followed by a further address representation of n bases; decoding the data representation into an integer value less than 3L that is a sum of a first addend and a second addend, wherein the data representation includes a first subsequence of bases encoding the first addend followed by a second subsequence of bases encoding the second addend; and storing, in a computer memory, the integer value.
Claims (34)
1. A method comprising:
reading, by way of random access, a physical nucleotide sequence of 2n+L bases to form a digital representation of the physical nucleotide sequence, wherein the reading involves amplifying the physical nucleotide sequence and sequencing the physical nucleotide sequence;
dividing the digital representation of the physical nucleotide sequence into an address representation of n bases, followed by a data representation of L bases, followed by a further address representation of n bases, wherein the address representation and the further address representation each are uncorrelated with one another, self-uncorrelated, and end with a particular base;
decoding the data representation into an integer value less than 3L that is a sum of a first addend and a second addend, wherein the data representation includes a first subsequence of bases encoding the first addend followed by a second subsequence of bases encoding the second addend, wherein the first addend is encoded based on mappings of subvalues of the first addend to n sets of bases respectively associated with the n bases of the address representation, wherein the second subsequence of bases is a ternary encoding of the second addend over a set of three bases not including the particular base, and wherein the data representation is uncorrelated with each of the address representation and the further address representation; and
storing, in a computer memory, the integer value.
2. The method of claim 1 , wherein the reading involves using a primer with the address representation to locate the physical nucleotide sequence within a plurality of nucleotide sequences, wherein the primer consists of approximately 50% guanine and cytosine content and is self-uncorrelated, wherein address representations of the plurality of nucleotide sequences are mutually uncorrelated with one another.
3. The method of claim 1 , wherein the ternary encoding of the second addend represents each of digits 0, 1, and 2, with respective different bases of the set of three bases.
4. The method of claim 1 , wherein the physical nucleotide sequence does not contain folding structures.
5. The method of claim 1 , wherein the n sets of bases exclude the particular base and the respectively associated bases of the address representation.
6. The method of claim 1 , wherein the physical nucleotide sequence consists of approximately 50% guanine and cytosine content.
7. The method of claim 6 , wherein the physical nucleotide sequence consisting of approximately 50% guanine and cytosine content comprises the physical nucleotide sequence being 0 to 3 bases away from 50% guanine and cytosine content.
8. The method of claim 1 , wherein L is less than n, the first subsequence of bases is zero length, and the second subsequence of bases is L length.
9. The method of claim 1 , wherein the n bases of the address representation are ordered such that no proper prefix of length j, for all j greater than or equal to a pre-defined integer k and less than n, is a suffix of the further address representation.
10. The method of claim 1 , further comprising:
before reading the physical nucleotide sequence, selecting the address representation and the further address representation from a population of address representations so that the data representation is uncorrelated with the address representation and the further address representation; and
synthesizing the physical nucleotide sequence to be the address representation followed by the data representation, followed by the further address representation.
11. The method of claim 1 , wherein the reading also involves locating an address sequence corresponding to the address representation in an unordered mixture of physical nucleotide sequences, and wherein the address sequence is associated with a data sequence corresponding to the data representation.
12. A system comprising:
means for reading, by way of random access, a physical nucleotide sequence of 2n+L bases to form a digital representation of the physical nucleotide sequence, wherein the reading involves amplifying the physical nucleotide sequence and sequencing the physical nucleotide sequence;
means for dividing the digital representation of the physical nucleotide sequence into an address representation of n bases, followed by a data representation of L bases, followed by a further address representation of n bases, wherein the address representation and the further address representation each are uncorrelated with one another, self-uncorrelated, and end with a particular base;
means for decoding the data representation into an integer value less than 3L that is a sum of a first addend and a second addend, wherein the data representation includes a first subsequence of bases encoding the first addend followed by a second subsequence of bases encoding the second addend, wherein the first addend is encoded based on mappings of subvalues of the first addend to n sets of bases respectively associated with the n bases of the address representation, wherein the second subsequence of bases is a ternary encoding of the second addend over a set of three bases not including the particular base, and wherein the data representation is uncorrelated with each of the address representation and the further address representation; and
means for storing, in a computer memory, the integer value.
13. The system of claim 12 , wherein the reading involves using a primer with the address representation to locate the physical nucleotide sequence within a plurality of nucleotide sequences, wherein the primer consists of approximately 50% guanine and cytosine content and is self-uncorrelated, wherein address representations of the plurality of nucleotide sequences are mutually uncorrelated with one another.
14. The system of claim 12 , wherein the ternary encoding of the second addend represents each of digits 0, 1, and 2, with respective different bases of the set of three bases.
15. The system of claim 12 , wherein the physical nucleotide sequence does not contain folding structures.
16. The system of claim 12 , wherein the n sets of bases exclude the particular base and the respectively associated bases of the address representation.
17. The system of claim 12 , wherein the physical nucleotide sequence consists of approximately 50% guanine and cytosine content, and wherein the physical nucleotide sequence consisting of approximately 50% guanine and cytosine content comprises the physical nucleotide sequence being 0 to 3 bases away from 50% guanine and cytosine content.
18. The system of claim 12 , wherein L is less than n, the first subsequence of bases is zero length, and the second subsequence of bases is L length.
19. The system of claim 12 , wherein the n bases of the address representation are ordered such that no proper prefix of length j, for all j greater than or equal to a pre-defined integer k and less than n, is a suffix of the further address representation.
20. A method comprising:
selecting an address representation and a further address representation, each specifying nucleotide sequences of n bases, wherein the address representation and the further address representation are mutually uncorrelated;
selecting a data representation of a nucleotide sequence of L bases, wherein the data representation encodes an integer value less than 3L that is a sum of a first addend and a second addend, wherein the data representation includes a first subsequence of bases encoding the first addend followed by a second subsequence of bases encoding the second addend, and wherein the data representation is uncorrelated with the address representation and the further address representation;
concatenating the address representation with the data representation and the further address representation to form a representation of a physical nucleotide sequence of 2n+L bases; and
synthesizing the physical nucleotide sequence.
Assignments (2)
CONFIRMATORY LICENSE
Recorded Apr 15, 2020
From: UNIVERSITY OF ILLINOIS, URBANA-CHAMPAIGN
To: NATIONAL SCIENCE FOUNDATION
Reel/Frame 052410/0375 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 18, 2019
From: MIA, JIAN; ZHAO, HUIMIN; MILENKOVIC, OLGICA; YUAN, YONGBO; YAZDI, S.M. HOSSEIN TABATABAEI
To: THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS
Reel/Frame 051322/0208 →
Continuity (3)
Continuation
15356118
· Nov 18, 2016
Provisional Application
62257273
· Nov 19, 2015
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