Methods for modulating the function of biological regulatory networks in health and disease by exploiting their memory properties

A system for determining whether a determining whether a gene regulatory network (GRN) exhibits memory, the system comprising at least one hardware processor that is programmed to perform one or more of the following steps:

• (A) simulating administering to the GRN an unconditioned stimuli (UCS) and determining whether the UCS triggers a response by the GRN;
• and
• (i) if the UCS does not trigger a response by the GRN, then repeating step (A) using another different UCS until the UCS triggers a response by the GRN;
• or
• (ii) if/when the UCS triggers a response by the GRN, then allowing the GRN to relax and simulating administering the UCS to the GRN and determining whether the GRN exhibits UCS-based memory (UM), and if the GRN does not exhibit UM then proceeding to step (B) or if the GRN exhibits UM then optionally completing the method;
• (B) simulating administering to the GRN a combination of an unconditioned stimulus (UCS) and a neutral stimulus (NS) and determining whether the combination of the UCS and the NS triggers a response by the GRN;
• and
• (i) if the combination of the UCS and the NS does not trigger a response by the GRN, then repeating step (B) using a combination of the UCS and another different NS until the combination of the UCS and the NS triggers a response by the GRN;
• or
• (ii) if/when the combination of the UCS and the NS triggers a response by the GRN, then allowing the GRN to relax and simulating administering the combination of the UCS and the NS and determining whether the GRN exhibits pairing memory (PM), and if the GRN does not exhibit PM then proceeding to step (C) or step (D) and if the GRN exhibits PM then optionally completing the method;
• (C) simulating administering to the GRN an unconditioned stimuli (UCS) and determining whether the UCS triggers a response by the GRN;
• and
• (i) if the UCS does not trigger a response by the GRN, then repeating step (C) using another different UCS until the UCS triggers a response by the GRN;
• and
• (ii) if/when the UCS triggers a response by the GRN, then allowing the GRN to relax and simulating administering a NS to the GRN and determining whether the GRN exhibits transfer memory (TM), and if the GRN does not exhibit TM then proceeding to step (D) or if the GRN exhibits TM then optionally completing the method;
• (D) simulating administering to the GRN a combination of an unconditioned stimulus (UCS) and a neutral stimulus (NS) and determining whether the combination of the UCS and the NS triggers a response by the GRN;
• and
• (i) if the combination of the UCS and the NS does not trigger a response by the GRN, then repeating step (D) using a different combination of another different UCS and/or another different NS until the combination of the UCS and the NS triggers a response by the GRN;
• or
• (ii) if/when the combination of the UCS and the NS triggers a response by the GRN, then allowing the GRN to relax and simulating administering the NS and determining whether the GRN exhibits associative memory (AM), and if the GRN does not exhibit AM then proceeding to step (E), or if the GRN does exhibit AM then optionally completing the method or optionally proceeding to step (D) (iii);
• or
• (iii) if the GRN exhibits AM, then allowing the GRN to relax and simulating administering the NS and determining whether the GRN exhibits long recall AM (LRAM), and if the GRN does not exhibit LRAM, then determining that the GRN exhibits short recall AM (SRAM) and optionally repeating step (D) using a different combination of another different UCS and/or another different NS until the GRN exhibits LRAM;
• and
• (E) after performing step (D), allowing the GRN to relax and simulating administering the NS and determining whether the GRN exhibits consolidation memory (CM), and if the GRN exhibits CM optionally completing the method or if the GRN does not exhibit CM then determining that the GRN does not exhibit memory.