Microbial engineering methods and systems for optimizing microbe fitness

Abstract

The present disclosure provides a microbe engineering platform that permits optimization of microbe fitness levels to optimize a microbe's suitability for industrial fermentation. The disclosed platform identifies an association between microbe properties and microbe fitness levels. The association between microbe properties and microbe fitness levels may be used to identify candidate microbes with desired fitness levels. The identified candidate microbes may be used to further optimize the industrial fermentation process.

1 . A computer-implemented method of identifying a collection of microbes based on fitness level, the method comprising:
 obtaining, by a computing device, image data relating to a plurality of collections of microbes, wherein one or more of the collections of microbes have a different fitness level than at least one of the other collections of microbes, and the image data is related to appearance of the plurality of collections of microbes;   determining, by a computing device, one or more values of one or more image data properties of each of the collections of microbes in a first set of the plurality of collections of microbes based at least in part upon the image data, wherein the first set comprises two or more collections of microbes;   determining an expressed value of fitness level of each of the collections of microbes in the first set;   identifying an association between the one or more image data properties and the fitness level, across the collections of microbes in the first set, based at least in part upon the one or more values of the one or more image data properties and the corresponding expressed value of fitness level for each collection of microbes in the first set; and   identifying a first collection of microbes based at least in part upon a predicted value of fitness level, wherein the predicted value of fitness level is based at least in part upon the association and one or more values of one or more image data properties of the first collection of microbes.   
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 , wherein the one or more image properties are related to one or more of the following properties of at least one corresponding collection of microbes: size, color, eccentricity, aspect ratio, opacity, edge roughness, edge sharpness, fluorescence, uniformity, topology, height, opacity profile, uniformity profile, fluorescence profile, height profile, distance to a nearest neighboring collection of microbes, growth rate, or local density of collections of microbes. 
     
     
         4 . The method of  claim 3 , wherein the fitness level is related to productivity. 
     
     
         5 . (canceled) 
     
     
         6 . The method of  claim 3 , wherein the fitness level is related to yield. 
     
     
         7 . (canceled) 
     
     
         8 . The method of  claim 1 , further comprising:
 identifying that a second collection of microbes includes contaminating microbes based at least in part upon one or more values of one or more image data properties of the second collection of microbes.   
     
     
         9 . The method of  claim 1 , further comprising:
 selecting the first collection of microbes for further processing.   
     
     
         10 . The method of  claim 9 , wherein the selected first collection of microbes comprises microbes with improved fitness relative to at least one collection of microbes in the plurality of collections of microbes. 
     
     
         11 . The method of  claim 9 , wherein the selected first collection of microbes comprises microbes with reduced fitness relative to at least one collection of microbes in the plurality of collections of microbes. 
     
     
         12 . The method of  claim 9 , further comprising:
 genetically modifying a microbe from the selected first collection of microbes.   
     
     
         13 . A system for identifying a collection of microbes based on fitness level, the system comprising:
 one or more processors; and   one or more memories operatively coupled to at least one of the one or more processors and having instructions stored thereon that, when executed by at least one of the one or more processors, cause the system to:
 obtain image data relating to a plurality of collections of microbes, 
 wherein one or more of the collections of microbes have a different fitness level than at least one of the other collections of microbes and the image data is related to appearance of the plurality of collections of microbes; 
 determine one or more values of one or more image data properties of each of the collections of microbes in a first set of the plurality of collections of microbes based at least in part upon the image data, wherein the first set comprises two or more collections of microbes; 
 determine an expressed value of fitness level of each of the collections of microbes in the first set; 
 identify an association between the one or more image data properties and the fitness level, across the collections of microbes in the first set, based at least in part upon the one or more values of the one or more image data properties and the corresponding expressed value of fitness level for each collection of microbes in the first set; and 
 identify a first collection of microbes based at least in part upon a predicted value of fitness level, wherein the predicted value of fitness level is based at least in part upon the association and one or more values of one or more image data properties of the first collection of microbes. 
   
     
     
         14 . (canceled) 
     
     
         15 . The system of  claim 13 , wherein the one or more image properties are related to one or more of the following properties of at least one corresponding collection of microbes: size, color, eccentricity, aspect ratio, opacity, edge roughness, edge sharpness, fluorescence, uniformity, topology, height, opacity profile, uniformity profile, fluorescence profile, height profile, distance to a nearest neighboring collection of microbes, growth rate, or local density of collections of microbes. 
     
     
         16 . The system of  claim 15 , wherein the fitness level is related to productivity. 
     
     
         17 . (canceled) 
     
     
         18 . The system of  claim 15 , wherein the fitness level is related to yield. 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . The system of  claim 13 , wherein at least one of the one or more memories operatively coupled to at least one of the one or more processors has instructions stored thereon that, when executed by at least one of the one or more processors, cause the system to:
 select the first collection of microbes for further processing.   
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . The system of  claim 21 , wherein at least one of the one or more memories operatively coupled to at least one of the one or more processors has instructions stored thereon that, when executed by at least one of the one or more processors, cause the system to:
 genetically modify a microbe from the selected first collection of microbes.   
     
     
         25 . One or more non-transitory computer readable media storing instructions for identifying a collection of microbes based on fitness level, wherein the instructions, when executed by one or more computing devices, cause at least one of the one or more computing devices to:
 obtain image data relating to a plurality of collections of microbes, wherein one or more of the collections of microbes have a different fitness level than at least one of the other collections of microbes, and the image data is related to appearance of the plurality of collections of microbes;   determine one or more values of one or more image data properties of each of the collections of microbes in a first set of the plurality of collections of microbes based at least in part upon the image data, wherein the first set comprises two or more collections of microbes;   determine an expressed value of fitness level of each of the collections of microbes in the first set;   identify an association between the one or more image data properties and the fitness level, across the collections of microbes in the first set, based at least in part upon the one or more values of the one or more image data properties and the corresponding expressed value of fitness level for each collection of microbes in the first set; and   identify a first collection of microbes based at least in part upon a predicted value of fitness level, wherein the predicted value of fitness level is based at least in part upon the association and one or more values of one or more image data properties of the first collection of microbes.   
     
     
         26 . (canceled) 
     
     
         27 . The computer readable media of  claim 25 , wherein the one or more image properties are related to one or more of the following properties of at least one corresponding collection of microbes: size, color, eccentricity, aspect ratio, opacity, edge roughness, edge sharpness, fluorescence, uniformity, topology, height, opacity profile, uniformity profile, fluorescence profile, height profile, distance to a nearest neighboring collection of microbes, growth rate, or local density of collections of microbes. 
     
     
         28 . The computer readable media of  claim 27 , wherein the fitness level is related to productivity. 
     
     
         29 . (canceled) 
     
     
         30 . The computer readable media of  claim 27 , wherein the fitness level is related to yield. 
     
     
         31 . (canceled) 
     
     
         32 . (canceled) 
     
     
         33 . The computer readable media of  claim 25 , storing instructions that, when executed by the one or more computing devices, cause at least one of the one or more computing devices to:
 select the first collection of microbes for further processing.   
     
     
         34 - 45 . (canceled)