Methods of populating data structures for use in evolutionary simulations

• US 7,430,477 B2
• Filed: 08/22/2005
• Issued: 09/30/2008
• Est. Priority Date: 10/12/1999
• Status: Expired due to Fees

• Current Assignee: Codexis, Inc.
• Original Assignee: Maxygen Inc.
• Inventors: Selifonov, Sergey A., Stemmer, Willem P. C.
• Primary Examiner(s): Kim; Young J.
• Application Number:
  US11/210,239
• Publication Number:
  US 20060047611A1
• Time in Patent Office: 1,135 Days
• Field of Search: None
• US Class Current: 702/19
• CPC Class Codes: G06N 3/126 Evolutionary algorithms, e.g. genetic algorithms or genetic programming
• CPC Class Codes: G16B 10/00 ICT specially adapted for evolutionary bioinformatics, e.g. phylogenetic tree construction or analysis
• CPC Class Codes: G16B 20/00 ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• CPC Class Codes: G16B 20/20 Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• CPC Class Codes: G16B 20/30 Detection of binding sites or motifs
• 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 30/20 Sequence assembly
• CPC Class Codes: G16B 40/00 ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding

Abstract

In particular, this invention provides novel methods of populating data structures for use in evolutionary modeling. In particular, this invention provides methods of populating a data structure with a plurality of character strings. The methods involve encoding two or more a biological molecules into character strings to provide a collection of two or more different initial character strings; selecting at least two substrings from the pool of character strings; concatenating the substrings to form one or more product strings about the same length as one or more of the initial character strings; adding the product strings to a collection of strings; and optionally repeating this process using one or more of the product strings as an initial string in the collection of initial character strings.

Claims

1. A method of identifying molecules for production, wherein the molecules are represented by concatenated strings, said method comprising:

i) encoding two or more related biological molecules into initial character strings wherein each of said biological molecules comprises at least about 10 subunits;

ii) selecting at least two substrings from said initial character strings;

iii) concatenating said substrings to form one or more product strings about the same length as one or more of the initial character stings;

v) determining sequence identities of at least one of the product strings relative to at least one initial character string; and

vi) selecting one or more product biological molecules for production, wherein the one more product biological molecules correspond to one or more of the product strings.

2. The method of claim 1, further comprising:

vii) producing the one or more product biological molecules.

3. The method of claim 1, wherein the two or more related biological molecules encoded into initial character strings in i) comprise two or more nucleic acids.

4. The method of claim 3, wherein at least one of said two or more nucleic acids has a nucleic acid sequence encoding a naturally occurring protein.

5. The method of claim 1, wherein said encoding comprises encoding two or more amino acid sequences into said character strings.

6. The method of claim 5, wherein said two or more amino acid sequences comprise an amino acid sequence encoding a naturally occurring protein.

7. The method of claim 1, wherein said initial character strings have at least 30% sequence identity with each other.

8. The method of claim 1, wherein at least one of the substrings selected in ii) has ends that occur in siring regions of about 3 to about 20 characters in the initial character string that have higher sequence identity with the corresponding region of another of said initial character strings than the overall sequence identity between the two initial character strings.

9. The method of claim 1, wherein said selecting in (ii) comprises selecting substrings such that the ends of said substrings occur in predefined motifs of about 4 to about 8 characters.

10. The method of claim 1, wherein said selecting in (ii) comprises aligning two or more of said initial character strings to maximize pairwise identity between two or more substrings of the initial character strings, and selecting a character that is a member of an aligned pair for the end of one of the two or more substrings.

11. The method of claim 1, wherein said method further comprises randomly altering one or more characters of said initial or product character strings.

12. The method of claim 11, wherein said method further comprises randomly selecting and altering one or more occurrences of a particular preselected character in said initial or product character strings.

13. The method of claim 1, wherein the initial character strings of (i) are related in that they encode the same gene or protein family but differ in sequence.

14. The method of claim 1, further comprising determining a computationally predicted property for molecules represented by the product strings.

15. The method of claim 1, wherein the product biological molecules are made in parallel in an array of vessels.

16. The method of claim 1, wherein the product biological molecules are made by assembly of oligonucleotides.