Exo-π-bonding to an ortho-carborane hypercarbon atom: systematic icosahedral cage distortions reflected in the structures of the fluoro-, hydroxy- and amino-carboranes, 1-X-2-Ph-1,2-C2B10H10 (X = F, OH or NH2) and related anions

The structures of derivatives of phenyl-ortho-carborane bearing on the second cage hypercarbon atom a pi-donor substituent (F, OH, O-, NH2, NH- and CH2-) were investigated by NMR, X-ray crystallography and computational studies. The molecular structures of these compounds, notably their cage C1-C2 distances and the orientations of their pi-donor substituents (OH, NH2, NH- and CH2-) show remarkable and systematic variations with the degree of exo pi-bonding, which varies as expected with the pi-donor characteristics of the substituent

miPIE: NGS-based Prediction of miRNA Using Integrated Evidence

Methods for the de novo identification of microRNA (miRNA) have been developed using a range of sequence-based features. With the increasing availability of next generation sequencing (NGS) transcriptome data, there is a need for miRNA identification that integrates both NGS transcript expression-based patterns as well as advanced genomic sequence-based methods. While miRDeep2 does examine the predicted secondary structure of putative miRNA sequences, it does not leverage many of the sequence-based features used in state-of-the-art de novo methods. Meanwhile, other NGS-based methods, such as miRanalyzer, place an emphasis on sequence-based features without leveraging advanced expression-based features reflecting miRNA biosynthesis. This represents an opportunity to combine the strengths of NGS-based analysis with recent advances in de novo sequence-based miRNA prediction. We here develop a method, microRNA Prediction using Integrated Evidence (miPIE), which integrates both expression-based and sequence-based features to achieve significantly improved miRNA prediction performance. Feature selection identifies the 20 most discriminative features, 3 of which reflect strictly expression-based information. Evaluation using precision-recall curves, for six NGS data sets representing six diverse species, demonstrates substantial improvements in prediction performance compared to three methods: miRDeep2, miRanalyzer, and mirnovo. The individual contributions of expression-based and sequence-based features are also examined and we demonstrate that their combination is more effective than either alone

A framework for improving microRNA prediction in non-human genomes

The prediction of novel pre-microRNA (miRNA) from genomic sequence has received considerable attention recently. However, the majority of studies have focused on the human genome. Previous studies have demonstrated that sensitivity (correctly detecting true miRNA) is sustained when human-trained methods are applied to other species, however they have failed to report the dramatic drop in specificity (the ability to correctly reject non-miRNA sequences) in

Updated free energy parameters increase microRNA prediction performance

Most de novo microRNA prediction tools rely on RNA structure prediction as a pre-screening step - only those sequences that exhibit miRNA-like hairpin structures are considered as putative miRNAs. However, little attention has been paid to the quality of this pre-screening step. This prescreening may unduly limit the sensitivity of the miRNA prediction method. We here demonstrate that leveraging recent advances in RNA structure prediction results in significant increases in overall miRNA prediction recall and precision

Trends in ortho-carboranes 1-X-2-R-1,2-C2B10H10 (R = Ph, Me) bearing an exo-CN-bonded substituent group (X = NO, N=NR ' or NHR '')

The preparation and crystal structures of four ortho-carboranyl-nitrogen compounds, PhCboNdouble bond; length as m-dashN(C6H4Me-4) (1), PhCboNHNH(C6H4Me-4) (2), MeCboNHNHPh (3) and PhCboNHOH (4) (Cbo = 1,2-C2B10H10; nitrogen groups at cage carbon C1, Ph or Me at C2), the last as a 1,4-dioxane solvate, are reported. Comparisons of their structures with those of other ortho-carboranyl-nitrogen systems studied earlier reveal further correlations between their cage C–C and exo-C–N bond distances and bond orders. Substituent orientations and bond distances (cage C1–C2, exo-C1–N) in RCboNHR′′ systems (R = Ph or Me at C2) are consistent with dative π-bonding from a nitrogen lone pair into the cage carbon p-AO otherwise responsible for cage C1–C2 σ bonding. Their C1–C2 bond distances are remarkably sensitive to the planar (sp2) or pyramidal (sp3) nature of the NHR′′ group. The Ndouble bond; length as m-dashO and Ndouble bond; length as m-dashNR′ residues in RCboX prefer to be orientated in plane with the cage C1–C2 in contrast to the RCboNHR′′ systems. Correlations between their cage C–C and exo-C–N bond distances and the 11B NMR chemical shifts of their antipodal boron atoms reflect the π-bonding characteristics of the nitrogen substituent

Exact string matching for MS/MS protein identification using the cell broadband engine

Current computational mass spectrometry techniques are limited by data acquisition techniques which often make sub-optimal use of mass spectrometry hardware and produce datasets which may not uniquely identify all proteins present in the biological sample. This is largely due to the offline nature of the data analysis, which is only conducted after acquisition is complete. Recently proposed online data analysis techniques which guide data acquisition, known as information-driven or directed tandem mass spectrometry (MS/MS) techniques, show promise in producing mass spectrometry datasets which uniquely identify a greater number of proteins, but these techniques have not yet been feasible due to the strict real-time requirements of mass spectrometry data acquisition. With the introduction of novel parallel programming models, such as the heterogeneous multicore Cell broadband engine (Cell B/E) architecture, information-driven MS/MS may now be possible. One of the biggest computational hurdles in creating an information-driven MS/MS system is the need to rapidly search proteomic databases for peptide fragments as they are identified by the mass spectrometer in real-time. Therefore, as a first step toward information-driven MS/MS, we have implemented a parallel string matching algorithm which is tailored to single peptide fragment searches over large proteomic databases. The Orthogonal Parabix algorithm introduced here has achieved sustained throughputs of 215.4 Gbps on a QS22 Cell blade representing a 4x speedup over leading general-purpose string matching algorithms on comparable hardware and more than 10x over an equivalent serial algorithm on a modern desktop processor. The peptide string matching algorithms developed here will form an integral part of a complete real-time information-driven MS/MS system which is expected to achieve higher-confidence protein identifications, particularly for low-abundance proteins and biomarkers

New synthetic and structural studies on nitroso-ortho-carboranes RCB10H10CNO and bis(ortho-carboranyl)amines (RCB10H10C)(2)NH (R = Ph or Me)

Improved procedures are reported for the preparation of nitroso-carboranes RCb°NO (Cb° = 1,2-C2B10H10; R = Ph, Me at cage carbon C2) in 44–77% yield, and of dicarboranylamines (RCb°)2NH in 55–65% yield by reactions between the lithio-carboranes, RCb°Li and nitrosyl chloride, NOCl, in cold mixtures of diethyl ether and either pentane (for RCb°NO) or dimethoxyethane (for (RCb°)2NH). Deprotonation of the amines by KOtBu in toluene in the presence of 18-crown-6, (CH2CH2O)6, affords the salts [K(18-crown-6)]+[(RCb°)2N]−. X-ray crystal structures of PhCb°NO, (PhCb°)2NH, (MeCb°)2NH and [K(18-crown-6)]+[(PhCb°)2N]− are described, and the bonding implications of their cage C…C distances (1.68, 1.80, 1.75 and 1.99 Å, respectively) are discussed. These species provide further striking examples of the remarkable capacity of the ortho-carborane cage to act as a sensitive indicator of the π-donor characteristics of ligands attached to its cage carbon atoms