Watermarking for data security in bioinformatic sequence analysis

• US 10,726,110 B2
• Filed: 02/28/2018
• Issued: 07/28/2020
• Est. Priority Date: 03/01/2017
• Status: Active Grant

• Current Assignee: Seven Bridges Genomics, Inc.
• Original Assignee: Seven Bridges Genomics, Inc.
• Inventors: Ghose, Kaushik, Kural, Deniz
• Primary Examiner(s): Do, Khang
• Application Number:
  US15/907,835
• Publication Number:
  US 20180253536A1
• Time in Patent Office: 881 Days
• CPC Class Codes: G06F 16/9024 Graphs; Linked lists G06F16/9027 takes precedence
• CPC Class Codes: G06F 21/16 Program or content traceability, e.g. by watermarking
• CPC Class Codes: G16B 30/00 ICT specially adapted for sequence analysis involving nucleotides or amino acids
• CPC Class Codes: G16B 30/10 Sequence alignment; Homology search
• CPC Class Codes: G16B 5/00 ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks
• CPC Class Codes: G16B 5/20 Probabilistic models
• CPC Class Codes: G16B 50/00 ICT programming tools or database systems specially adapted for bioinformatics
• CPC Class Codes: G16B 50/40 Encryption of genetic data

Abstract

Embodiments of the invention protect information stored in graph-based sequence references by “watermarking” the graph with uniquely identifiable information. The watermark identifies the graph or version thereof in a detectable but nonintrusive manner. In one embodiment, insertions and/or deletions are introduced into regions of the graph.

Claims

1. A system for modifying a deoxyribonucleic acid (DNA) sequence corresponding to a genome or portion thereof and represented as a reference graph, the system comprising:

a memory partition for storing the sequence; and

a watermarking module for modifying the sequence by introducing a watermarking artifact therein, the watermarking artifact comprising at least one of (a) a plurality of variants not found in natural genomic DNA, (b) a variant introduced in a repeat sequence other than the first of a plurality of repeat sequences in a repetitive region, (c) at least one sequence no longer than 30 bp not found in natural genomic DNA, or (d) metadata associated with variants in the reference graph, wherein the graph includes multiple paths at least one of which corresponds to a natural DNA sequence and another of which includes the watermarking artifact.

2. The system of claim 1, wherein the watermarking artifact is introduced in a region within 100 bp, 250 bp, or 500 bp of centromere DNA.

3. The system of claim 1, wherein the at least one variant is in a k-mer with k ranging from 15-30 bp.

4. The system of claim 1, wherein the metadata includes variant allele frequency information.

5. The system of claim 1, wherein a watermarking artifact comprises a frameshift in an essential gene.

6. The system of claim 1, wherein a watermarking artifact encodes an alternative protein sequence.

7. The system of claim 6, wherein the alternative protein sequence spells a word in a language.

8. The system of claim 1, wherein a variant introduced in a repeat sequence comprises a variant introduced in the middle of a repeat sequence.

9. The system of claim 1, wherein a variant not found in natural genomic DNA comprises a private variant found only in a single individual.

10. The system of claim 9, wherein the private variant is identified from a trio experiment.

11. A method of watermarking a deoxyribonucleic acid (DNA) sequence corresponding to a genome or portion thereof and represented as a reference graph and stored as a data structure in a computer memory, the method comprising modifying the memory contents corresponding to the sequence by introducing a watermarking artifact therein, the watermarking artifact comprising at least one of (a) a plurality of variants not found in natural genomic DNA, (b) a variant introduced in a repeat sequence other than the first of a plurality of repeat sequences in a repetitive region, (c) at least one sequence no longer than 30 bp not found in natural genomic DNA, or (d) metadata associated with variants in the reference graph, wherein the graph includes multiple paths at least one of which corresponds to a natural DNA sequence and another of which includes the watermarking artifact.

12. The method of claim 11, wherein the watermarking artifact is introduced in a region within 100 bp, 250 bp, or 500 bp of centromere DNA.

13. The method of claim 11, wherein the metadata includes variant allele frequency information.

14. The method of claim 11, wherein a watermarking artifact comprises a frameshift in an essential gene.

15. The method of claim 11, wherein a watermarking artifact encodes an alternative protein sequence.

16. The method of claim 11, wherein a variant introduced in a repeat sequence comprises a variant introduced in the middle of a repeat sequence.

17. The method of claim 11, wherein a variant not found in natural genomic DNA comprises a private variant found only in a single individual.