A Logic Programming Language for Computational Nucleic Acid Devices

Abstract

Computational nucleic acid devices show great potential for enabling a broad range of biotechnology applications, including smart probes for molecular biology research, in vitro assembly of complex compounds, high-precision in vitro disease diagnosis and, ultimately, computational theranostics inside living cells. This diversity of applications is supported by a range of implementation strategies, including nucleic acid strand displacement, localization to substrates, and the use of enzymes with polymerase, nickase, and exonuclease functionality. However, existing computational design tools are unable to account for these strategies in a unified manner. This paper presents a logic programming language that allows a broad range of computational nucleic acid systems to be designed and analyzed. The language extends standard logic programming with a novel equational theory to express nucleic acid molecular motifs. It automatically identifies matching motifs present in the full system, in order to apply a specified transformation expressed as a logical rule. The language supports the definition of logic predicates, which provide constraints that need to be satisfied in order for a given rule to be applied. The language is sufficiently expressive to encode the semantics of nucleic strand displacement systems with complex topologies, together with computation performed by a broad range of enzymes, and is readily extensible to new implementation strategies. Our approach lays the foundation for a unifying framework for the design of computational nucleic acid devices.

Dynamic and scalable DNA-based information storage

“…Similar capabilities in DNA-based systems would significantly increase their value and competitiveness. ssDNA overhangs have previously been used to execute computations in the context of toehold switches [40][41][42][43] , and we therefore hypothesized they could be used to implement instorage file operations. As a proof-of-principle, we implemented locking, unlocking, renaming, and deleting files and showed these operations could be performed at room temperature (Fig.…”

A domain-level DNA strand displacement reaction enumerator allowing arbitrary non-pseudoknotted secondary structures

“…VisualDSD is well-known and well-developed software for enumeration and simulation of DNA strand displacement systems [15][16][17][18]20]. The enumeration semantics is based on a process calculus for modelling DNA strand displacement, originally allowing a restrictive class of secondary structures, e.g.…”

“…no hairpin-loops, no branched structures) and a built-in set of common intended reaction rules between those structures. More recently, VisualDSD can interpret a programming language called LogicDSD [18,20], which has been used to enumerate and simulate a much wider class of DNA related systems. For example, it supports DNA structures with arbitrary pairing between two complementary domains (including hairpins, branched structures and so-called pseudoknotted conformations; see definition 2.3), it supports enzymatic processes such as DNA degradation, etc.…”

Dynamic DNA-based information storage

“…Similar capabilities in DNA-based systems would significantly increase their value and competitiveness. DNA has previously been used to execute computations [23][24][25] , and we therefore hypothesized toeholds could be used to implement in-storage file operations. As a proof-of-principle, we implemented locking, unlocking, renaming, and deleting files and showed these operations could be performed at room temperature (Figure 4).…”