Towards the genomic sequence code of DNA fragility for machine learning.

Genomic DNA breakages and the subsequent insertion and deletion mutations are important contributors to genome instability and linked diseases. Unlike the research in point mutations, the relationship between DNA sequence context and the propensity for strand breaks remains elusive. Here, by analyzing the differences and commonalities across myriads of genomic breakage datasets, we extract the sequence-linked rules and patterns behind DNA fragility. We show the overall deconvolution of the sequence influence into short-, mid- and long-range effects, and the stressor-dependent differences in defining the range and compositional effects on DNA fragility. We summarize and release our feature compendium as a library that can be seamlessly incorporated into genomic machine learning procedures, where DNA fragility is of concern, and train a generalized DNA fragility model on cancer-associated breakages. Structural variants (SVs) tend to stabilize regions in which they emerge, with the effect most pronounced for pathogenic SVs. In contrast, the effects of chromothripsis are seen across regions less prone to breakages. We find that viral integration may bring genome fragility, particularly for cancer-associated viruses. Overall, this work offers novel insights into the genomic sequence basis of DNA fragility and presents a powerful machine learning resource to further enhance our understanding of genome (in)stability and evolution.

Periodically-arrayed ferroelectric nanostructures induced by dislocation structures in strontium titanate.

A dislocation induces ferroelectricity around it in incipient ferroelectric SrTiO3 due to some reasons such as electro-mechanical coupling and it being a one-dimensional ferroelectric nanostructure. Furthermore, this microstructure is arrayed periodically in the material and dislocation structures such as a dislocation wall are formed. Due to these facts, periodically-arrayed ferroelectric nanostructures, which show various intriguing polarization configurations and functionalities depending on the internal periodic structure, may be fabricated by dislocations. The phase-field simulation exhibits that a ferroelectric nano-region induced by the strain concentration and incidental electric field around a dislocation connects with each other in a dislocation wall. As a result, a periodic ferroelectric nano-region, which is a periodically-arrayed ferroelectric nanostructure embedded in paraelectric matrices, is formed. Our findings provide a new pathway for the fabrication of novel functional nanodevices in ferroelectric systems.

Topological ferroelectric nanostructures induced by mechanical strain in strontium titanate.

Ferroelectric materials exhibit novel topological polarization configurations due to geometric confinements originating from the material shapes and interfaces at the nanoscale. In this study, we demonstrate that those nontrivial topological ferroelectric nanostructures can be tailored in paraelectric nanoporous materials by mechanical loads using phase-field modeling. That is, in nanoporous strontium titanate, periodically-arrayed ferroelectric nanostructures in the shape of networks are formed due to strain concentrations by mechanical loads, and topological polarization configurations, such as hierarchical vortices, woven fabrics and nested structures of spiral like Hopf fibration, are stabilized in the structures strongly affected by the pore arrangements. Our work indicates that various ferroelectric nanostructures with novel shapes and topologies can be designed by controlling the pore arrangements and strain conditions in nanoporous SrTiO3, and thus provides a new pathway to realize novel topological ferroelectric nanostructures, which are essential for future nanodevices.

Quantum mechanical electronic and geometric parameters for DNA k-mers as features for machine learning.

We are witnessing a steep increase in model development initiatives in genomics that employ high-end machine learning methodologies. Of particular interest are models that predict certain genomic characteristics based solely on DNA sequence. These models, however, treat the DNA as a mere collection of four, A, T, G and C, letters, dismissing the past advancements in science that can enable the use of more intricate information from nucleic acid sequences. Here, we provide a comprehensive database of quantum mechanical (QM) and geometric features for all the permutations of 7-meric DNA in their representative B, A and Z conformations. The database is generated by employing the applicable high-cost and time-consuming QM methodologies. This can thus make it seamless to associate a wealth of novel molecular features to any DNA sequence, by scanning it with a matching k-meric window and pulling the pre-computed values from our database for further use in modelling. We demonstrate the usefulness of our deposited features through their exclusive use in developing a model for A->C mutation rates.

Ultrasmall Polar Skyrmions and Merons in SrTiO3 Heterostructures by Polaron Engineering.

Topological objects with skyrmionic textures in ferroelectrics, i.e., polar skyrmions, are promising technological paradigms in next-generation electronic devices. While breakthrough discoveries of stable polar skyrmions approximately ten nanometers in size have been very recently witnessed in complex systems, such a nontrivial topological order in ferroelectrics inevitably disappears below the ferroelectric critical size of several nanometers. Herein, we propose a strategy to overcome this limitation and achieve ultrasmall and isolated polar skyrmions by engineering excess-electron polarons in otherwise nonferroelectric SrTiO3 heterostructures. Our first-principle calculations demonstrate that a polaron localized at a SrTiO3 surface induces a Neel-type polar skyrmion as small as 1.8 nanometers attributed to the effect of atomic-scale surface roughness. Furthermore, we show that this polar topological structure is tunable by the choice of heterostructures and by the mechanical approach, which undergoes a phase transition to a meron state in the twisted boundary and to an antiskyrmion state in the surface with external shear strain, respectively. Such ultraminiaturization of skyrmions and their transitions unexpectedly unravels the formula of ultrasmall topological orders originating from the interplay between an electron polaron and structural symmetry breaking, which is completely different from the common mechanism of geometric confinement for larger-scale skyrmions. Our results not only provide a mechanism for the exploration of polar skyrmions and their rich topological transitions but also hold potential for ultrahigh-density memories.

Emergence of non-trivial polar topologies hidden in singular stress field in SrTiO3: topological strain-field engineering.

Discovery of non-trivial topological structures in condensed matters holds promise in novel technological paradigms. In contrast to ferromagnetics, where a variety of topological structures such as vortex, meron, and skyrmion have been discovered, only few topological structures can exist in ferroelectrics due to the lack of non-collinear interaction like the Dzyaloshinskii-Moriya interaction in ferromagnetics. Here, we demonstrate that polarization structures with a wide range of topological numbers (winding numbernfrom -3 to +1) can be mechanically excited and designed by the mode-I singular stress field formed near the crack-tip in incipient ferroelectric SrTiO3. Our phase-field simulations based on Ginzburg-Landau theory successfully reveals that the near-tip polar topology is driven by the flexoelectric coupling with intense strain gradient at the tip, while a variety of the far-field topological structures is triggered by a collaboration between the electrostrictive and flexoelectric effects. The strain (gradient) field analysis further shows that the unexpected topological characters are implied in the singular stress field, which develops a variety of polar topologies near the crack tip. Therefore, our work provides a novel insight into the unusual interplay between mechanical- and ferroelectric-topologies, i.e. 'topological strain-field engineering', which paves the way to the mechanical design of functional topologies in the matter.