Entromics -- thermodynamics of sequence dependent base incorporation into DNA reveals novel long-distance genome organization

TL;DR

This paper introduces entromics, a thermodynamic framework based on DNA sequence-dependent incorporation chemical potential, revealing new insights into genome organization and constraints through a combination of graph theory and statistical thermodynamics.

Contribution

It develops a novel thermodynamic model of DNA base incorporation, introducing the concept of incorporation entropy and linking it to genome organization and evolution.

Findings

Identification of a new physical property of DNA, the incorporation chemical potential.

Derivation of formulas to compute this potential from DNA sequences.

Revelation of long-distance genome organization patterns through thermodynamic restrictions.

Abstract

Zero mode waveguide technology of next generation sequencing demonstrated sequence-dependence of the enzymatic reaction, incorporating a base into the genomic DNA. We show that these experimental results indicate existence of a previously uncharacterized physical property of DNA, the incorporation reaction chemical potential {\Delta}{\mu}. We use the combination of graph theory and statistical thermodynamics to derive entromics - a series of results providing the thermodynamic model of {\Delta}{\mu}. We also show that {\Delta}{\mu}i is quantitatively characterized as incorporation entropy. We present formulae for computing {\Delta}{\mu} from the genome DNA sequence. We then derive important restrictions on DNA properties and genome assembly that follow from thermodynamic properties of {\Delta}{\mu}. Finally, we show how these genome assembly restrictions lead directly to the evolution of detectable coherences in incorporation entropy along the entire genome. Examples of entromic applications, demonstrating functional and biological importance are shown.