Woo, Sung Sik Kim, Jaewook Sarpeshkar, Rahul 2024-01-19T23:03:09Z 2024-01-19T23:03:09Z 2021-09-03 2018-04 1932-4545 https://pubs.kist.re.kr/handle/201004/121554 Prior work has shown that compact analog circuits can faithfully represent and model fundamental biomolecular circuits via efficient log-domain cytomorphic transistor equivalents. Such circuits have emphasized basis functions that are dominant in genetic transcription and translation networks and deoxyribonucleic acid (DNA)-protein binding. Here, we report a system featuring digitally programmable 0.35 mu m BiCMOS analog cytomorphic chips that enable arbitrary biochemical reaction networks to be exactly represented thus enabling compact and easy composition of protein networks as well. Since all biomolecular networks can be represented as chemical reaction networks, our protein networks also include the former genetic network circuits as a special case. The cytomorphic analog protein circuits use one fundamental association-dissociation-degradation building-block circuit that can be configured digitally to exactly represent any zeroth-, first-, and second-order reaction including loading, dynamics, nonlinearity, and interactions with other building-block circuits. To address a divergence issue caused by random variations in chip fabrication processes, we propose a unique way of performing computation based on total variables and conservation laws, which we instantiate at both the circuit and network levels. Thus, scalable systems that operate with finite error over infinite time can be built. We show how the building-block circuits can be composed to form various network topologies, such as cascade, fan-out, fan-in, loop, dimerization, or arbitrary networks using total variables. We demonstrate results from a system that combines interacting cytomorphic chips to simulate a cancer pathway and a glycolysis pathway. Both simulations are consistent with conventional software simulations. Our highly parallel digitally programmable analog cytomorphic systems can lead to a useful design, analysis, and simulation tool for studying arbitrary large-scale biological networks in systems and synthetic biology. English IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC EXACT STOCHASTIC SIMULATION SYSTEMS OSCILLATIONS GLYCOLYSIS COMPUTER CIRCUITS BIOLOGY A Digitally Programmable Cytomorphic Chip for Simulation of Arbitrary Biochemical Reaction Networks Article 10.1109/TBCAS.2017.2781253 1 IEEE TRANSACTIONS ON BIOMEDICAL CIRCUITS AND SYSTEMS, v.12, no.2, pp.360 - 378 IEEE TRANSACTIONS ON BIOMEDICAL CIRCUITS AND SYSTEMS 12 2 360 378 scie scopus 000428547600010 2-s2.0-85041670868 Engineering, Biomedical Engineering, Electrical & Electronic Engineering Article EXACT STOCHASTIC SIMULATION SYSTEMS OSCILLATIONS GLYCOLYSIS COMPUTER CIRCUITS BIOLOGY Biochemical reaction biological circuit simulation cancer circuits cellular models cytomorphic glycolysis reaction networks systems biology synthetic biology transistor models