Patent ID: 8005620

Claim:
A method for constructing a variant set for modifying a biopolymer of interest, the method comprising: a) identifying 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; b) selecting a first plurality of variants of the biopolymer of interest thereby forming a variant set, wherein said variant set comprises a subset of said biopolymer sequence space; c) measuring a property of all or a portion of the variants in the variant set; and d) modeling, using a suitably programmed computer, 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 the portion of the variants in the variant set, wherein the sequence-activity relationship has the form Y=f ( w 1 x 1 ,w 2 x 2 , . . . w i x i ) wherein, Y is a quantitative measure of the property; x i is a descriptor of a substitution, a combination of substitutions, or a component of one or more substitutions, at one or more positions in the plurality of positions; w i is a weight applied to the descriptor x i ; and f( ) is a mathematical function, and wherein the modeling comprises: i) optimizing, using a suitably programmed computer, the sequence-activity relationship by adjusting individual weights w i for each said descriptor x i using a refinement algorithm that minimizes the difference between the predicted values and the real values of Y from partial data, wherein the partial data is the first plurality of variants with either (1) individual sequences left out on a random basis or (2) individual substitutions at positions in the plurality of positions left out on a random basis, and ii) repeating the optimizing i) a plurality of times thereby obtaining, for each respective substitution or combination of substitutions x i , (a) an average value for the weight w i describing a relative or absolute contribution of the respective substitution or combination of substitutions x i to Y, and (b) a standard deviation, variance or other measure of confidence in the weight w i describing the relative or absolute contribution of the respective substitution or combination of substitutions x i to Y.