System and method for nucleic acid sequence design
AssigneeCalifornia Institute of Technology
InventorsNiles A. Pierce, Brian R. Wolfe, Joseph Zadeh
Life of this patent
Estimating the term…
Abstract
Described herein are systems and processes for designing the sequence of one or more interacting nucleic acid strands intended to adopt a target secondary structure at equilibrium. The target secondary structure is decomposed into a binary tree and candidate mutations are evaluated on leaf nodes of the tree. During a process of leaf optimization, defect-weighted mutation sampling is used to select each candidate mutation position with a probability proportional to its contribution to an ensemble defect of the leaf. Subsequences of the tree are then merged, moving up the tree until a final nucleotide sequence of interest is determined that has the target secondary structure at equilibrium.
Claims21
An electronic system having one or more processors and configured for optimizing a sequence of a nucleic acid strand to adopt a specific target secondary structure at equilibrium, comprising:
- an input for receiving a target secondary structure;
- code running on a processor and configured to decompose the target secondary structure at split points into a tree of parental nodes, child nodes and leaf nodes wherein each split point is formed within a duplex stem of the target structure;
- code running on a processor and configured to determine a leaf nucleotide sequence of the target structure at each leaf node in the tree;
- and
- code running on a processor and configured to recurse the nodes of the tree and merge the determined leaf nucleotide sequences at each node to optimize the nucleotide sequence of a nucleic acid strand that adopts the specific target secondary structure at equilibrium.
An electronic system comprising one or more processors configured for optimizing a sequence of a polynucleotide strand to adopt a specific target secondary structure at equilibrium, comprising:
- an input for receiving a target secondary structure;
- means running on a processor for decomposing the target secondary structure at split points into a tree of parental nodes, child nodes and leaf nodes wherein each split point is formed within a duplex stem of the target structure;
- means running on a processor for determining a leaf nucleotide sequence of the target structure at each leaf node in the tree;
- and
- means running on a processor for recursing the nodes of the tree and merge the determined leaf nucleotide sequences at each node to optimize the nucleotide sequence of a nucleic acid strand that adopts the specific target secondary structure at equilibrium.
An electronic system comprising one or more processors configured for optimizing a sequence of a polynucleotide strand to adopt a specific target secondary structure at equilibrium, comprising:
- an input for receiving a target secondary structure;
- one or more processors configured to perform a method comprising:
- decomposing the target secondary structure at split points into a tree of parental nodes, child nodes and leaf nodes wherein each split point is formed within a duplex stem of the target structure;
- determining a leaf nucleotide sequence of the target structure at each leaf node in the tree;
- and
- recursing the nodes of the tree and merge the determined leaf nucleotide sequences at each node to optimize the nucleotide sequence of a nucleic acid strand that adopts the specific target secondary structure at equilibrium.
Dependencies are inferred from the claim text.