KIRMES: kernel-based identification of regulatory modules in euchromatic sequences

Motivation: Understanding transcriptional regulation is one of the main challenges in computational biology. An important problem is the identification of transcription factor (TF) binding sites in promoter regions of potential TF target genes. It is typically approached by position weight matrix-based motif identification algorithms using Gibbs sampling, or heuristics to extend seed oligos. Such algorithms succeed in identifying single, relatively well-conserved binding sites, but tend to fail when it comes to the identification of combinations of several degenerate binding sites, as those often found in cis-regulatory modules

The Role of Mobile Phones in Governance-Driven Technology Exports in Sub-Saharan Africa

This study assesses how the mobile phone influences governance to improve information and communication technology (ICT) exports in Sub-Saharan Africa with data from 2000-2012. The empirical evidence is based on Generalised Method of Moments and three main governance concepts are used, namely: (i) institutional (comprising the rule of law and corruption-control); (ii) political (involving political stability/no violence and voice & accountability) and (iii) economic (including regulation quality and government effectiveness) governance. The following findings are established. First, there are positive net effects on ICT goods exports from independent interactions between mobile phones and ‘political stability’ ‘voice and accountability’ and corruption-control. Second, significant net effects are not apparent from independent interactions between mobile phones and government effectiveness, regulation quality and the rule of law. Theoretical and practical implications are discussed

Dithiothreitol (DTT) acts as a specific, UV-inducible cross-linker in elucidation of protein-RNA interactions.

Protein-RNA cross-linking by UV irradiation at 254 nm wavelength has been established as an unbiased method to identify proteins in direct contact with RNA, and has been successfully applied to investigate the spatial arrangement of protein and RNA in large macromolecular assemblies, e.g. ribonucleoprotein-complex particles (RNPs). The mass spectrometric analysis of such peptide-RNA cross-links provides high resolution structural data to the point of mapping protein-RNA interactions to specific peptides or even amino acids. However, the approach suffers from the low yield of cross-linking products, which can be addressed by improving enrichment and analysis methods. In the present article, we introduce dithiothreitol (DTT) as a potent protein-RNA cross-linker. In order to evaluate the efficiency and specificity of DTT, we used two systems, a small synthetic peptide from smB protein incubated with U1 snRNA oligonucleotide and native ribonucleoprotein complexes from S. cerevisiae. Our results unambiguously show that DTT covalently participates in cysteine-uracil crosslinks, which is observable as a mass increment of 151.9966 Da (C4H8S2O2) upon mass spectrometric analysis. DTT presents advantages for cross-linking of cysteine containing regions of proteins. This is evidenced by comparison to experiments where (tris(2-carboxyethyl)phosphine) is used as reducing agent, and significantly less cross-links encompassing cysteine residues are found. We further propose insertion of DTT between the cysteine and uracil reactive sites as the most probable structure of the cross-linking products

Clinical and non-targeted metabolomic profiling of homozygous carriers of transcription factor 7-like 2 variant rs7903146.

An important role of the type 2 diabetes risk variant rs7903146 in TCF7L2 in metabolic actions of various tissues, in particular of the liver, has recently been demonstrated by functional animal studies. Accordingly, the TT diabetes risk allele may lead to currently unknown alterations in human. Our study revealed no differences in the kinetics of glucose, insulin, C-peptide and non-esterified fatty acids during an OGTT in homozygous participants from a German diabetes risk cohort (n = 1832) carrying either the rs7903146 CC (n = 15) or the TT (n = 15) genotype. However, beta-cell function was impaired for TT carriers. Covering more than 4000 metabolite ions the plasma metabolome did not reveal any differences between genotypes. Our study argues against a relevant impact of TCF7L2 rs7903146 on the systemic level in humans, but confirms the role in the pathogenesis of type 2 diabetes in humans as a mechanism impairing insulin secretion

Automated label-free quantification of metabolites from liquid chromatography-mass spectrometry data.

Liquid chromatography coupled to mass spectrometry (LC-MS) has become a standard technology in metabolomics. In particular, label-free quantification based on LC-MS is easily amenable to large-scale studies and thus well suited to clinical metabolomics. Large-scale studies, however, require automated processing of the large and complex LC-MS datasets. We present a novel algorithm for the detection of mass traces and their aggregation into features (i.e. all signals caused by the same analyte species) that is computationally efficient and sensitive and that leads to reproducible quantification results. The algorithm is based on a sensitive detection of mass traces, which are then assembled into features based on mass-to-charge spacing, co-elution information, and a support vector machine-based classifier able to identify potential metabolite isotope patterns. The algorithm is not limited to metabolites but is applicable to a wide range of small molecules (e.g. lipidomics, peptidomics), as well as to other separation technologies. We assessed the algorithm's robustness with regard to varying noise levels on synthetic data and then validated the approach on experimental data investigating human plasma samples. We obtained excellent results in a fully automated data-processing pipeline with respect to both accuracy and reproducibility. Relative to state-of-the art algorithms, ours demonstrated increased precision and recall of the method. The algorithm is available as part of the open-source software package OpenMS and runs on all major operating systems