Htp genomic engineering platform

A method, comprising:

• (a) generating, by a processor, a promoter swap host cell library having a plurality of engineered host cells, each engineered host cell from the plurality of engineered host cells having a promoter-gene combination such that the plurality of engineered host cells having a plurality of promoter-gene combinations, each promoter-gene combination from the plurality of promoter-gene combinations having one or more promoters from a promoter ladder operably linked to a target gene present in a base host cell from a plurality of base host cells, the promoter ladder including a plurality of promoters exhibiting different expression profiles in the plurality of base host cells;
• (b) sending, by the processor, instructions to automated liquid and particle handling robotics to cause the automated liquid and particle handling robotics to manipulate liquid or particles added to or removed from cultures having the plurality of base host cells to create the plurality of engineered host cells;
• (c) determining, by the processor and based on screening and selecting engineered host cells from the plurality of engineered host cells based on a phenotypic performance metric, a set of promoter-gene combinations (1) from the plurality of promoter-gene combinations and (2) that confer a greater degree of a desired phenotype associated with the phenotypic performance metric than the remaining promoter-gene combinations from the plurality of promoter-gene combinations;
• and
• (d) generating, by the processor, an output identifying the set of promoter-gene combinations.

A processor-readable non-transitory medium storing code representing instructions to be executed by a processor, the code comprising code to cause the processor to:

• (a) generate a promoter swap host cell library defining a first plurality of engineered host, each engineered host cell from the first plurality of engineered host cells having a genetic variation such that the plurality of engineered host cells have a plurality of genetic variations, each genetic variation from the plurality of genetic variations having one or more promoters from a promoter ladder operably linked to a target gene present in a base host cell from a plurality of base host cells, the promoter ladder including a plurality of promoters exhibiting different expression profiles in the plurality of base host cells;
• (b) determine, based on screening and selecting engineered host cells from the first plurality of engineered host cells based on a phenotypic performance metric, a set of genetic variations (1) from the plurality of genetic variations and (2) that confer a greater degree of a desired phenotype associated with the phenotypic performance metric than the remaining genetic variations from the plurality of genetic variations;
• and
• (c) generate a subsequent promoter swap host cell library to define a second plurality of engineered host cells that each have a combination of genetic variations selected from the set of genetic variations and present in at least two engineered host cells from the first plurality of engineered host cells.

A processor-readable non-transitory medium storing code representing instructions to be executed by a processor, the code comprising code to cause the processor to:

• (a) generate a promoter swap host cell library having a plurality of engineered host cells, each engineered host cell from the plurality of engineered host cells having a promoter-gene combination such that the plurality of engineered host cells having a plurality of promoter-gene combinations, each promoter-gene combination from the plurality of promoter-gene combinations having one or more promoters from a promoter ladder operably linked to a target gene present in a base host cell from a plurality of base host cells, the promoter ladder including a plurality of promoters exhibiting different expression profiles in the plurality of base host cells;
• (b) send instructions to automated liquid and particle handling robotics to cause the automated liquid and particle handling robotics to manipulate liquid or particles added to or removed from cultures having the plurality of base host cells to create the plurality of engineered host cells;
• (c) determine, based on screening and selecting engineered host cells from the plurality of engineered host cells based on a phenotypic performance metric, a set of promoter-gene combinations (1) from the plurality of promoter-gene combinations and (2) that confer a greater degree of a desired phenotype associated with the phenotypic performance metric than the remaining promoter-gene combinations from the plurality of promoter-gene combinations;
• and
• (d) generate an output identifying the set of promoter-gene combinations.