High performance multi-input microrna sensors and uses thereof

A cell state classifier, the cell state classifier comprising:

• (i) a first sensor circuit comprising a promoter operably linked to a nucleotide sequence encoding a first activator and one or more target sites for a first set of microRNAs;
• (ii) a second sensor circuit comprising:
• (a) a promoter operably linked to a nucleotide sequence encoding a second activator one or more target sites for a second microRNA, and one or more target sites for a first regulatory microRNA that is different from any of the first set of microRNAs or the second microRNA;
• (b) a promoter that is activated by the second activator of (ii)(a), operably linked to a nucleotide sequence encoding a first repressor and one or more target sites for the second microRNA of (ii)(a);
• wherein the second activator is different from the first activator, and
• (iii) a first signal circuit comprising:
• (a) a first activatable/repressible promoter that is activated by the first activator of (i) or repressed by the first repressor of (ii)(b), operably linked to a nucleotide sequence encoding a first output molecule and to a nucleotide sequence encoding the first regulatory microRNA;
• and
• (b) one or more target sites for any one of the first set of microRNAs of (i).