Systems and methods for antibody engineering

A method of weighting a plurality of selection rules for use in selecting a plurality of positions in a biopolymer of interest and, for each respective position in said plurality of positions, one or more substitutions for the respective positions, the method comprising:

• a) identifying, using said plurality of selection rules, a plurality of positions in a biopolymer of interest and, for each respective position in said plurality of positions, one or more substitutions for the respective position, wherein
• the plurality of positions and the one or more substitutions for each respective position in the plurality of positions collectively define a biopolymer sequence space, and
• the contribution of each respective rule in said plurality of rules to said biopolymer sequence space is independently weighted by a rule weight in a plurality of rule weights corresponding to the respective rule;
• b) selecting a variant set, wherein said variant set comprises a plurality of variants of said biopolymer of interest and wherein said variant set is a subset of said biopolymer sequence space;
• c) measuring a property of all or a portion of the variants in said variant set;
• d) modeling a sequence-activity relationship between (i) one or more substitutions at one or more positions of the biopolymer of interest represented by the variant set and (ii) the property measured for all or said portion of the variants in the variant set;
• and
• e) adjusting one or more rule weights in said plurality of rule weights based on a comparison, for each respective variant in the variant set, (i) a value assigned to the respective variant by the sequence-activity relationship, and (ii) a score assigned by the plurality of rules to the respective variant;
• f) repeating said identifying, selecting, measuring, modeling, and adjusting for each biopolymer of interest in a plurality of biopolymers of interest.

A computer program product for use in conjunction with a computer system, the computer program product comprising a computer readable storage medium and a computer program mechanism embedded therein, the computer program mechanism comprising:

• a knowledge base comprising a plurality of rules;
• and
• an expert module for constructing a variant set for a biopolymer of interest, the expert module comprising:
• instructions for identifying, using said plurality of rules, a plurality of positions in said biopolymer of interest and, for each respective position in said plurality of positions, one or more substitutions for the respective position, wherein the plurality of positions and the one or more substitutions for each respective position in the plurality of positions collectively define a biopolymer sequence space;
• instructions for selecting a variant set, wherein said variant set comprises a plurality of variants of said biopolymer of interest and wherein said variant set is a subset of said biopolymer sequence space;
• instructions for measuring or receiving a measurement a property of all or a portion of the variants in said variant set;
• instructions for modeling a sequence-activity relationship between (i) one or more substitutions at one or more positions of the biopolymer of interest represented by the variant set and (ii) the property measured for all or said portion of the variants in the variant set;
• and
• instructions for redefining said variant set to comprise variants that include substitutions in said plurality of positions that are selected based on a function of said sequence-activity relationship.

A computer system comprising:

• a central processing unit;
• a memory, coupled to the central processing unit, the memory storing a knowledge base and an expert module, wherein
• the knowledge base comprises a plurality of rules;
• and
• the expert module is for constructing a variant set for a biopolymer of interest and comprises:
• instructions for identifying, using said plurality of rules, a plurality of positions in said biopolymer of interest and, for each respective position in said plurality of positions, one or more substitutions for the respective position, wherein the plurality of positions and the one or more substitutions for each respective position in the plurality of positions collectively define a biopolymer sequence space;
• instructions for selecting a variant set, wherein said variant set comprises a plurality of variants of said biopolymer of interest and wherein said variant set is a subset of said biopolymer sequence space;
• instructions for measuring or receiving a measurement a property of all or a portion of the variants in said variant set;
• instructions for modeling a sequence-activity relationship between (i) one or more substitutions at one or more positions of the biopolymer of interest represented by the variant set and (ii) the property measured for all or said portion of the variants in the variant set;
• and
• instructions for redefining said variant set to comprise variants that include substitutions in said plurality of positions that are selected based on a function of said sequence-activity relationship.