Patent ID: 8635029

Claim:
A method 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 said biopolymer of interest thereby forming a first variant set, wherein said first variant set comprises a first subset of said biopolymer sequence space; c) measuring a property of all or a portion of the variants in said first variant set; d) modeling, using a suitably programmed computer, a sequence-activity relationship on a computer between (i) one or more substitutions at one or more positions of the biopolymer of interest represented by the first variant set described as a plurality of descriptors x and a plurality of weights w, each weight w i in the plurality of weights w being applied to a corresponding descriptor x i in the plurality of descriptors x; and (ii) the property Y measured for all or said portion of the variants in the first variant set, 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 in the sequence-activity relationship 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 descriptor x i , (a) an average value for the weight w i describing a relative or absolute contribution of the respective descriptor 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 descriptor x i to Y, and e) defining a second variant set for the biopolymer of interest, wherein the second variant set is a second subset of said biopolymer sequence space, the second variant set comprises a variant of the biopolymer of interest having a first substitution in a position in the plurality of positions, wherein the first substitution is selected on the basis that the average weight w i corresponding to the first substitution is at least one standard deviation above neutrality as determined by the modeling d).