Application of Logic Synthesis Toward the Inference and Control of Gene Regulatory Networks

In the quest to understand cell behavior and cure genetic diseases such as cancer, the fundamental approach being taken is undergoing a gradual change. It is becoming more acceptable to view these diseases as an engineering problem, and systems engineering approaches are being deployed to tackle genetic diseases. In this light, we believe that logic synthesis techniques can play a very important role. Several techniques from the field of logic synthesis can be adapted to assist in the arguably huge effort of modeling cell behavior, inferring biological networks, and controlling genetic diseases. Genes interact with other genes in a Gene Regulatory Network (GRN) and can be modeled as a Boolean Network (BN) or equivalently as a Finite State Machine (FSM). As the expression of genes deter- mine cell behavior, important problems include (i) inferring the GRN from observed gene expression data from biological measurements, and (ii) using the inferred GRN to explain how genetic diseases occur and determine the ”best” therapy towards treatment of disease. We report results on the application of logic synthesis techniques that we have developed to address both these problems. In the first technique, we present Boolean Satisfiability (SAT) based approaches to infer the predictor (logical support) of each gene that regulates melanoma, using gene expression data from patients who are suffering from the disease. From the output of such a tool, biologists can construct targeted experiments to understand the logic functions that regulate a particular target gene. Our second technique builds upon the first, in which we use a logic synthesis technique; implemented using SAT, to determine gene regulating functions for predictors and gene expression data. This technique determines a BN (or family of BNs) to describe the GRN and is validated on a synthetic network and the p53 network. The first two techniques assume binary valued gene expression data. In the third technique, we utilize continuous (analog) expression data, and present an algorithm to infer and rank predictors using modified Zhegalkin polynomials. We demonstrate our method to rank predictors for genes in the mutated mammalian and melanoma networks. The final technique assumes that the GRN is known, and uses weighted partial Max-SAT (WPMS) towards cancer therapy. In this technique, the GRN is assumed to be known. Cancer is modeled using a stuck-at fault model, and ATPG techniques are used to characterize genes leading to cancer and select drugs to treat cancer. To steer the GRN state towards a desirable healthy state, the optimal selection of drugs is formulated using WPMS. Our techniques can be used to find a set of drugs with the least side-effects, and is demonstrated in the context of growth factor pathways for colon cancer

Основи схемотехніки електронних систем

Basics of circuitry are stated, principles of operation are considered, it is given calculations of analog, digital and pulse devices of electronic systems, based on semiconductor devices, integrated operational amplifiers and integrated logic circuits of TTL, MOS, CMOS types, construction principles of systems of control by electronics devices based on microprocessors and microcontrollers. For students of institutions of higher education. It can be useful for specialists on electronic engineering, specializing in the area of development, fabrication and maintenance of electronic systems and devices

Proceedings of the 26th International Symposium on Theoretical Aspects of Computer Science (STACS'09)

The Symposium on Theoretical Aspects of Computer Science (STACS) is held alternately in France and in Germany. The conference of February 26-28, 2009, held in Freiburg, is the 26th in this series. Previous meetings took place in Paris (1984), Saarbr¨ucken (1985), Orsay (1986), Passau (1987), Bordeaux (1988), Paderborn (1989), Rouen (1990), Hamburg (1991), Cachan (1992), W¨urzburg (1993), Caen (1994), M¨unchen (1995), Grenoble (1996), L¨ubeck (1997), Paris (1998), Trier (1999), Lille (2000), Dresden (2001), Antibes (2002), Berlin (2003), Montpellier (2004), Stuttgart (2005), Marseille (2006), Aachen (2007), and Bordeaux (2008). ..

Proceedings of the 22nd Conference on Formal Methods in Computer-Aided Design – FMCAD 2022

The Conference on Formal Methods in Computer-Aided Design (FMCAD) is an annual conference on the theory and applications of formal methods in hardware and system verification. FMCAD provides a leading forum to researchers in academia and industry for presenting and discussing groundbreaking methods, technologies, theoretical results, and tools for reasoning formally about computing systems. FMCAD covers formal aspects of computer-aided system design including verification, specification, synthesis, and testing

Proceedings of the 22nd Conference on Formal Methods in Computer-Aided Design – FMCAD 2022

The Conference on Formal Methods in Computer-Aided Design (FMCAD) is an annual conference on the theory and applications of formal methods in hardware and system verification. FMCAD provides a leading forum to researchers in academia and industry for presenting and discussing groundbreaking methods, technologies, theoretical results, and tools for reasoning formally about computing systems. FMCAD covers formal aspects of computer-aided system design including verification, specification, synthesis, and testing