Chromosome Three-Dimensional Structure Reconstruction: An Iterative ShRec3D Algorithm.

The three-dimensional (3D) structure of chromosomes is of great significance to ensure that the genome performs various functions (e.g., gene expression) correctly and replicates and separates correctly in mitosis. Since the emergence of Hi-C in 2009, a new experimental technique in molecular biology, researchers have been paying more and more attention to the reconstruction of chromosome 3D structure. To reconstruct the 3D structure of chromosomes based on Hi-C experimental data, many algorithms have been proposed, among which ShRec3D is one of the most outstanding. In this article, an iterative ShRec3D algorithm is presented to greatly improve the native ShRec3D algorithm. Experimental results show that our algorithm can significantly promote the performance of ShRec3D, and this improvement is applicable to almost all data noise range and signal coverage range, so it is universal.

Chromatin 3D structure reconstruction with consideration of adjacency relationship among genomic loci.

BACKGROUND: Chromatin 3D conformation plays important roles in regulating gene or protein functions. High-throughout chromosome conformation capture (3C)-based technologies, such as Hi-C, have been exploited to acquire the contact frequencies among genomic loci at genome-scale. Various computational tools have been proposed to recover the underlying chromatin 3D structures from in situ Hi-C contact map data. As connected residuals in a polymer, neighboring genomic loci have intrinsic mutual dependencies in building a 3D conformation. However, current methods seldom take this feature into account. RESULTS: We present a method called ShNeigh, which combines the classical MDS technique with local dependence of neighboring loci modeled by a Gaussian formula, to infer the best 3D structure from noisy and incomplete contact frequency matrices. We validated ShNeigh by comparing it to two typical distance-based algorithms, ShRec3D and ChromSDE. The comparison results on simulated Hi-C dataset showed that, while keeping the high-speed nature of classical MDS, ShNeigh can recover the true structure better than ShRec3D and ChromSDE. Meanwhile, ShNeigh is more robust to data noise. On the publicly available human GM06990 Hi-C data, we demonstrated that the structures reconstructed by ShNeigh are more reproducible between different restriction enzymes than by ShRec3D and ChromSDE, especially at high resolutions manifested by sparse contact maps, which means ShNeigh is more robust to signal coverage. CONCLUSIONS: Our method can recover stable structures in high noise and sparse signal settings. It can also reconstruct similar structures from Hi-C data obtained using different restriction enzymes. Therefore, our method provides a new direction for enhancing the reconstruction quality of chromatin 3D structures.

The role of sp2 and sp3 hybridized bonds on the structural, mechanical, and electronic properties in a hard BN framework.

A first-principles approach is used to systematically investigate the role of sp2 and sp3 hybridized bonds on the structural, mechanical, and electronic properties in a new BN phase (denoted Hex-(BN)12). Hex-(BN)12 has the same number of sp2 and sp3 hybridized atoms. The calculated cohesion energy, phonon frequencies, and elastic constants unambiguously confirm the structural stability of this compound. Due to the different types of hybridization and B-N covalent bonds with ionic characteristics, Hex-(BN)12 has unequal bond lengths and bond angles in these hybrid orbitals. These cause the relative energetic stability to be slightly lower than c-BN and w-BN. The hardness of Hex-(BN)12 is estimated to range from 33 to 40 GPa. The bond-breaking order under stress is sp3-sp3, sp2-sp3, and sp2-sp2. DFT calculations with the gradient approximation (GGA) and HSE06 functional indicate the electronic structure contains an indirect band gap at 3.21 and 4.42 eV, respectively. The electronic states in the region near the Fermi level primarily arise from the 2p orbitals in sp2-hybridized atoms. In general, sp3 bonded B and N atoms guarantee higher mechanical properties, and sp2 bonded atoms ensure ductility and even conductivity, although all changes vary with spatial structure. Hex-(BN)12 can be obtained from multilayer yne-BN, and BN nanosheets, nanotubes and nanoribbons under pressure.