Unconstrained mining of transcript data reveals increased alternative splicing complexity in the human transcriptome.

Mining massive amounts of transcript data for alternative splicing information is paramount to help understand how the maturation of RNA regulates gene expression. We developed an algorithm to cluster transcript data to annotated genes to detect unannotated splice variants. A higher number of alternatively spliced genes and isoforms were found compared to other alternative splicing databases. Comparison of human and mouse data revealed a marked increase, in human, of splice variants incorporating novel exons and retained introns. Previously unannotated exons were validated by tiling array expression data and shown to correspond preferentially to novel first exons. Retained introns were validated by tiling array and deep sequencing data. The majority of retained introns were shorter than 500 nt and had weak polypyrimidine tracts. A subset of retained introns matching small RNAs and displaying a high GC content suggests a possible coordination between splicing regulation and production of noncoding RNAs. Conservation of unannotated exons and retained introns was higher in horse, dog and cow than in rodents, and 64% of exon sequences were only found in primates. This analysis highlights previously bypassed alternative splice variants, which may be crucial to deciphering more complex pathways of gene regulation in human.

Madelung Formalism for Electron Spill-Out in Nonlocal Nanoplasmonics.

Current multiscale plasmonic systems pose a modeling challenge. Classical macroscopic theories fail to capture quantum effects in such systems, whereas quantum electrodynamics is impractical given the total size of the experimentally relevant systems, as the number of interactions is too large to be addressed one by one. To tackle the challenge, in this paper we propose to use the Madelung form of the hydrodynamic Drude model, in which the quantum effect electron spill-out is incorporated by describing the metal-dielectric interface using a super-Gaussian function. The results for a two-dimensional nanoplasmonic wedge are correlated to those from nonlocal full-wave numerical calculations based on a linearized hydrodynamic Drude model commonly employed in the literature, showing good qualitative agreement. Additionally, a conformal transformation perspective is provided to explain qualitatively the findings. The methodology described here may be applied to understand, both numerically and theoretically, the modular inclusions of additional quantum effects, such as electron spill-out and nonlocality, that cannot be incorporated seamlessly by using other approaches.