Automatic intrinsic DNA curvature computation from AFM images

Critical information on several biological processes such as DNA-protein interactions and DNA transcription can be derived from analysis of DNA curvature. Under thermal perturbation, the curvature is composed of static and dynamic contributions, thus, can be described as the sum of intrinsic curvature and a fluctuation contribution. Without considering thermal agitations, the DNA curvature is reducible to the intrinsic component, which is a function of the DNA nucleotide sequence only. In this paper, we present an automated algorithm to determine the DNA intrinsic curvature profiles and the molecular spatial orientations in Atomic Force Microscope images. The algorithm allows to reconstruct the intrinsic curvature profile by filtering the thermal contribution. It detects fragment orientation on atomic force microscope images without labels with a percentage of correct molecular-orientation detection of 96.79% in computer-generated benchmarks, for molecules with a high curvature peak. The automated algorithm reconstructs the intrinsic curvature profile of DNA molecules with a mean square error of 3.8122·10^-4 rads over a profile with a central peak value of 0.196 rads, and 6.1·10^-3 rads over a curvature profile with two symmetric peaks of about 0.08rads. Moreover, it correctly detects the location of the peaks in the molecules with a deviation of about 1% of molecule length.