Landscape of SNPs-mediated lncRNA structural variations and their implication in human complex diseases.

An increasing number of functional studies shows that long noncoding RNAs (lncRNAs) are involved in many aspects of cellular physiology and fulfills a wide variety of regulatory roles at almost every stage of gene expression. A major feature of lncRNAs is the highly folded modular domains in transcripts. With improved modeling and definition, it is now feasible to explore and gain novel insights into the structural-functional relationship of lncRNAs and their association with complex human diseases. In this study, we utilized an automatic computational pipeline to scan lncRNA architecture at the genome-wide scale and to obtain a landscape of functional domains. An accurate alignment algorithm was performed to identify 40 triple pairs between single-nucleotide polymorphisms (SNPs), lncRNAs and diseases. In order to detect the potential contribution of a lncRNA's modular character, we estimated and evaluated structural rearrangements, which were derived from disease-associated SNPs. In addition, we focused on annotating and comparing the global and local heterogeneity of the wild-type and mutant lncRNAs. Assessing lncRNA architecture has yielded how variations in structured regions impact the molecular mechanisms of lncRNAs and how SNPs disturb binding and recruiting ability. These observations are the first glimpse of the 'lncRNA structurome' and make it possible to robustly explore and assemble intricate space conformation and their stress variation. This result also successfully demonstrates that lncRNA transcripts contain a complex structural landscape and highlights the proposed contribution of lncRNA structure in controlling RNA functions and disease mechanisms.

Evaluation of drug efficacy based on the spatial position comparison of drug-target interaction centers.

The spatial position and interaction of drugs and their targets is the most important characteristics for understanding a drug's pharmacological effect, and it could help both in finding new and more precise treatment targets for diseases and in exploring the targeting effects of the new drugs. In this work, we develop a computational pipeline to confirm the spatial interaction relationship of the drugs and their targets and compare the drugs' efficacies based on the interaction centers. First, we produce a 100-sample set to reconstruct a stable docking model of the confirmed drug-target pairs. Second, we set 5.5 Å as the maximum distance threshold for the drug-amino acid residue atom interaction and construct 3-dimensional interaction surface models. Third, by calculating the spatial position of the 3-dimensional interaction surface center, we develop a comparison strategy for estimating the efficacy of different drug-target pairs. For the 1199 drug-target interactions of the 649 drugs and 355 targets, the drugs that have similar interaction center positions tend to have similar efficacies in disease treatment, especially in the analysis of the 37 targeted relationships between the 15 known anti-cancer drugs and 10 target molecules. Furthermore, the analysis of the unpaired anti-cancer drug and target molecules suggests that there is a potential application for discovering new drug actions using the sampling molecular docking and analyzing method. The comparison of the drug-target interaction center spatial position method better reflect the drug-target interaction situations and could support the discovery of new efficacies among the known anti-cancer drugs.

Location deviations of DNA functional elements affected SNP mapping in the published databases and references.

The recent extensive application of next-generation sequencing has led to the rapid accumulation of multiple types of data for functional DNA elements. With the advent of precision medicine, the fine-mapping of risk loci based on these elements has become of paramount importance. In this study, we obtained the human reference genome (GRCh38) and the main DNA sequence elements, including protein-coding genes, miRNAs, lncRNAs and single nucleotide polymorphism flanking sequences, from different repositories. We then realigned these elements to identify their exact locations on the genome. Overall, 5%-20% of all sequence element locations deviated among databases, on the scale of kilobase-pair to megabase-pair. These deviations even affected the selection of genome-wide association study risk-associated genes. Our results implied that the location information for functional DNA elements may deviate among public databases. Researchers should take care when using cross-database sources and should perform pilot sequence alignments before element location-based studies.

LncRNA Structural Characteristics in Epigenetic Regulation.

The rapid development of new generation sequencing technology has deepened the understanding of genomes and functional products. RNA-sequencing studies in mammals show that approximately 85% of the DNA sequences have RNA products, for which the length greater than 200 nucleotides (nt) is called long non-coding RNAs (lncRNA). LncRNAs now have been shown to play important epigenetic regulatory roles in key molecular processes, such as gene expression, genetic imprinting, histone modification, chromatin dynamics, and other activities by forming specific structures and interacting with all kinds of molecules. This paper mainly discusses the correlation between the structure and function of lncRNAs with the recent progress in epigenetic regulation, which is important to the understanding of the mechanism of lncRNAs in physiological and pathological processes.