Microbial strain design system and methods for improved large-scale production of engineered nucleotide sequences

Abstract

The generation of a factory order includes receiving an expression indicating an operation on a first sequence operand and a second sequence operand. The first sequence operand represents multiple biological sequence parts, and the second sequence operand represents at least one biological sequence part. The expression is evaluated to a sequence specification, which represents modifications to at least one biological sequence, and comprises a data structure representing (a) the first and second sequence operands, (b) one or more first-level operations to be performed on one or more first-level sequence operands, and (c) one or more second-level operations, the execution of at least one of which resolves values of at least one of the first-level sequence operands. A factory order is generated based upon execution of at least one first-level operation and at least one second-level operation.

What is claimed is: 
     
         1 .- 72 . (canceled) 
     
     
         73 . A method comprising:
 (i) receiving, at a computing device, an expression indicating an operation on a first sequence operand and a second sequence operand, wherein the first sequence operand represents a plurality of biological sequence parts, and the second sequence operand represents at least one biological sequence part;   (ii) executing, by a computing device, instructions to evaluate the expression to a sequence specification, wherein the sequence specification comprises a data structure representing (a) the first and second sequence operands, (b) one or more first-level operations to be performed on one or more first-level sequence operands, and (c) one or more second-level operations, the execution of at least one of which resolves a plurality of values of at least one of the one or more first-level sequence operands, wherein the sequence specification represents modifications to one or more biological sequences; and   (iii) generating a factory order based upon execution, by a computing device, of one or more of the first-level operations and one or more of the second-level operations.   
     
     
         74 . The method of  claim 73 , wherein, based on the factory order, biological sequence parts are assembled into a plurality of biological sequences. 
     
     
         75 . The method of  claim 73 , wherein a plurality of biological sequences assembled from biological sequence parts based on the factory order are assayed to determine their performance based upon the modifications represented by the sequence specification. 
     
     
         76 . The method of  claim 73 , wherein based on the factory order, a plurality of engineered cells, having a plurality of phenotypes that are based upon the modifications represented by the sequence specification, are produced. 
     
     
         77 . The method of  claim 73 , wherein:
 (iv) based on the factory order, biological sequence parts are assembled into a plurality of biological sequences; and   (v) the plurality of biological sequences are introduced into a plurality of cells to produce a plurality of engineered cells having a plurality of phenotypes that are based upon the modifications represented by the sequence specification.   
     
     
         78 . The method of  claim 77 , wherein:
 a subset of the plurality of engineered cells is selected based on assayed phenotypic performance of the plurality of engineered cells within the subset;   modifications are selected based on correlations between modifications represented in the sequence specification and assayed phenotypic performance of engineered cells;   a second plurality of biological sequences is assembled based upon performing (i)-(iv) with the first and second sequence operands, the one or more first-level operations, and the one or more second-level operations being based on the selected modifications; and   the second plurality of biological sequences is introduced into the subset of engineered cells.   
     
     
         79 . The method of  claim 73 , wherein the one or more biological sequences comprise one or more nucleotide sequences. 
     
     
         80 . The method of  claim 73 , wherein the data structure further includes a plurality of parameters relating to how at least one of the one or more first-level operations or at least one of the one or more second-level operations is to be reified, and the factory order includes information concerning the plurality of parameters. 
     
     
         81 . The method of  claim 73 , wherein the first-level sequence operand is expressed as a sequence specification indicating at least one operation to be performed on a plurality of sequence parts. 
     
     
         82 . The method of  claim 73 , wherein at least one of the one or more first-level operands is represented as a data structure that represents one or more second-level operations to be performed on one or more second-level operands. 
     
     
         83 . The method of  claim 73 , wherein the one or more biological sequences comprise more than one 100 biological sequences. 
     
     
         84 . A system comprising:
 one or more memories storing instructions; and   one or more processors, operatively coupled to the one or more memories, to execute the instructions to cause:   (i) receiving an expression indicating an operation on a first sequence operand and a second sequence operand, wherein the first sequence operand represents a plurality of biological sequence parts, and the second sequence operand represents at least one biological sequence part;   (ii) evaluating the expression to a sequence specification, wherein the sequence specification comprises a data structure representing (a) the first and second sequence operands, (b) one or more first-level operations to be performed on one or more first-level sequence operands, and (c) one or more second-level operations, the execution of at least one of which resolves a plurality of values of at least one of the one or more first-level sequence operands, wherein the sequence specification represents modifications to one or more biological sequences; and   (iii) generating a factory order based upon execution of one or more of the first-level operations and one or more of the second-level operations.   
     
     
         85 . The system of  claim 84 , wherein the instructions, when executed cause: based on the factory order, biological sequence parts are assembled into a plurality of biological sequences. 
     
     
         86 . The system of  claim 84 , wherein the instructions, when executed cause: a plurality of biological sequences assembled from biological sequence parts based on the factory order are assayed to determine their performance based upon the modifications represented by the sequence specification. 
     
     
         87 . The system of  claim 84 , wherein the instructions, when executed cause: based on the factory order, a plurality of engineered cells, having a plurality of phenotypes that are based upon the modifications represented by the sequence specification, are produced. 
     
     
         88 . The system of  claim 84 , wherein the instructions, when executed cause:
 (iv) based on the factory order, biological sequence parts are assembled into a plurality of biological sequences; and   (v) the plurality of biological sequences are introduced into a plurality of cells to produce a plurality of engineered cells having a plurality of phenotypes that are based upon the modifications represented by the sequence specification.   
     
     
         89 . The system of  claim 88 , wherein the instructions, when executed cause:
 a subset of the plurality of engineered cells is selected based on assayed phenotypic performance of the plurality of engineered cells within the subset;   modifications are selected based on correlations between modifications represented in the sequence specification and assayed phenotypic performance of engineered cells;   a second plurality of biological sequences is assembled based upon performing (i)-(iv) with the first and second sequence operands, the one or more first-level operations, and the one or more second-level operations being based on the selected modifications; and   the second plurality of biological sequences is introduced into the subset of engineered cells.   
     
     
         90 . The system of  claim 84 , wherein the one or more biological sequences comprise one or more nucleotide sequences. 
     
     
         91 . The system of  claim 84 , wherein the data structure further includes a plurality of parameters relating to how at least one of the one or more first-level operations or at least one of the one or more second-level operations is to be reified, and the factory order includes information concerning the plurality of parameters. 
     
     
         92 . The system of  claim 84 , wherein the first-level sequence operand is expressed as a sequence specification indicating at least one operation to be performed on a plurality of sequence parts. 
     
     
         93 . The system of  claim 84 , wherein at least one of the one or more first-level operands is represented as a data structure that represents one or more second-level operations to be performed on one or more second-level operands. 
     
     
         94 . The system of  claim 84 , wherein the one or more biological sequences comprise more than one 100 biological sequences. 
     
     
         95 . One or more non-transitory computer readable media storing instructions that, when executed, cause:
 (i) receiving an expression indicating an operation on a first sequence operand and a second sequence operand, wherein the first sequence operand represents a plurality of biological sequence parts, and the second sequence operand represents at least one biological sequence part;   (ii) evaluating the expression to a sequence specification, wherein the sequence specification comprises a data structure representing (a) the first and second sequence operands, (b) one or more first-level operations to be performed on one or more first-level sequence operands, and (c) one or more second-level operations, the execution of at least one of which resolves a plurality of values of at least one of the one or more first-level sequence operands, wherein the sequence specification represents modifications to one or more biological sequences; and   (iii) generating a factory order based upon execution of one or more of the first-level operations and one or more of the second-level operations.   
     
     
         96 . The one or more computer readable media of  claim 95 , wherein the instructions, when executed cause: based on the factory order, biological sequence parts are assembled into a plurality of biological sequences. 
     
     
         97 . The one or more computer readable media of  claim 95 , wherein the instructions, when executed cause: a plurality of biological sequences assembled from biological sequence parts based on the factory order are assayed to determine their performance based upon the modifications represented by the sequence specification. 
     
     
         98 . The one or more computer readable media of  claim 95 , wherein the instructions, when executed cause: based on the factory order, a plurality of engineered cells, having a plurality of phenotypes that are based upon the modifications represented by the sequence specification, are produced. 
     
     
         99 . The one or more computer readable media of  claim 95 , wherein the instructions, when executed cause:
 (iv) based on the factory order, biological sequence parts are assembled into a plurality of biological sequences; and   (v) the plurality of biological sequences are introduced into a plurality of cells to produce a plurality of engineered cells having a plurality of phenotypes that are based upon the modifications represented by the sequence specification.   
     
     
         100 . The one or more computer readable media of  claim 99 , wherein the instructions, when executed cause:
 a subset of the plurality of engineered cells is selected based on assayed phenotypic performance of the plurality of engineered cells within the subset;   modifications are selected based on correlations between modifications represented in the sequence specification and assayed phenotypic performance of engineered cells;   a second plurality of biological sequences is assembled based upon performing (i)-(iv) with the first and second sequence operands, the one or more first-level operations, and the one or more second-level operations being based on the selected modifications; and   the second plurality of biological sequences is introduced into the subset of engineered cells.   
     
     
         101 . The one or more computer readable media of  claim 95 , wherein the one or more biological sequences comprise one or more nucleotide sequences. 
     
     
         102 . The one or more computer readable media of  claim 95 , wherein the data structure further includes a plurality of parameters relating to how at least one of the one or more first-level operations or at least one of the one or more second-level operations is to be reified, and the factory order includes information concerning the plurality of parameters. 
     
     
         103 . The one or more computer readable media of  claim 95 , wherein the first-level sequence operand is expressed as a sequence specification indicating at least one operation to be performed on a plurality of sequence parts. 
     
     
         104 . The one or more computer readable media of  claim 95 , wherein at least one of the one or more first-level operands is represented as a data structure that represents one or more second-level operations to be performed on one or more second-level operands. 
     
     
         105 . The one or more computer readable media of  claim 95 , wherein the one or more biological sequences comprise more than one 100 biological sequences.