Methods, systems, and software for identifying functional biomolecules
AssigneeMaxygen, Inc.
InventorRichard John Fox
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Abstract
The present invention generally relates to methods of rapidly and efficiently searching biologically-related data space. More specifically, the invention includes methods of identifying bio-molecules with desired properties, or which are most suitable for acquiring such properties, from complex bio-molecule libraries or sets of such libraries. The invention also provides methods of modeling sequence-activity relationships. As many of the methods are computer-implemented, the invention additionally provides digital systems and software for performing these methods.
Claims16
A method for identifying nucleotides for variation in nucleic acids encoding a protein variant library in order to impact a desired activity, said method comprising:
- (a) receiving data characterizing a training set of a protein variant library, wherein the data provides activity and nucleotide sequence information for each protein variant in the training set;
- (b) from the data, developing a sequence activity model for predicting activity as a function of independent variables each specifying the presence or absence of a nucleotide, identity of said nucleotide, and position of said nucleotide in a nucleotide sequence,
- wherein the sequence-activity model includes one or more non-linear terms, each representing an interaction between two or more amino acid residues in a protein sequence;
- and
- (c) using the sequence activity model to rank positions in the nucleotide sequence and nucleotide types at the ranked positions in the nucleotide sequence in order of impact on the desired activity;
- (d) using the ranking to identify one or more nucleotides, in the nucleotide sequence, that are to be varied or fixed in order to impact the desired activity, wherein the nucleotides to be varied include codons encoding particular amino acids,
- wherein operations (a)-(d) are performed by executing instructions on a computer system programmed to perform said operations.
A computer program product comprising a tangible machine readable medium on which is provided program code for identifying nucleotides for variation in nucleic acids encoding a protein variant library in order to impact a desired activity, said program code comprising:
- (a) code for receiving data characterizing a training set of a protein variant library, wherein the data provides activity and nucleotide sequence information for each protein variant in the training set;
- (b) code for developing, from said data, a sequence activity model for predicting activity as a function of independent variables each specifying the presence or absence of a nucleotide, identity of said nucleotide, and position of said nucleotide in a nucleotide sequence,
- wherein the sequence-activity model includes one or more non-linear terms, each representing an interaction between two or more amino acid residues in a protein sequence;
- and
- (c) code for using the sequence activity model to rank positions in the nucleotide sequence and nucleotide types at the ranked positions in the nucleotide sequence in order of impact on the desired activity;
- (d) code for using the ranking to identify one or more nucleotides, in the nucleotide sequence, that are to be varied or fixed in order to impact the desired activity wherein the nucleotides to be varied include codons encoding particular amino acids.
Dependencies are inferred from the claim text.