Many fields of science and industry depend on efficient production of active protein using heterologous expression in Escherichia coli. The solubility of proteins upon expression is dependent on ...their amino acid sequence. Prediction of solubility from sequence is therefore highly valuable. We present a novel machine‐learning‐based model called PROSO II which makes use of new classification methods and growth in experimental data to improve coverage and accuracy of solubility predictions. The classification algorithm is organized as a two‐layered structure in which the output of a primary Parzen window model for sequence similarity and a logistic regression classifier of amino acid k‐mer composition serve as input for a second‐level logistic regression classifier. Compared with previously published research our model is trained on five times more data than used by any other method before (82 000 proteins). When tested on a separate holdout set not used at any point of method development our server attained the best results in comparison with other currently available methods: accuracy 75.4%, Matthew’s correlation coefficient 0.39, sensitivity 0.731, specificity 0.759, gain (soluble) 2.263. In summary, due to utilization of cutting edge machine learning technologies combined with the largest currently available experimental data set the PROSO II server constitutes a substantial improvement in protein solubility predictions. PROSO II is available at http://mips.helmholtz‐muenchen.de/prosoII.
The solubility of proteins upon heterologous expression in Escherichia coli is dependent on their amino acid sequence. Prediction of solubility from sequence is therefore highly valuable. We present a web‐server, PROSO II, which makes use of novel classification methods and growth in experimental data to improve significantly the coverage and accuracy of solubility predictions (accuracy 75.4%, MCC 0.39 gain (soluble) 2.263).
High-quality mapping of genomic regions and genes between two organisms is an indispensable prerequisite for evolutionary analyses and comparative genomics. Existing approaches to this problem focus ...on either delineating orthologs or finding extended sequence regions of common evolutionary origin (syntenic blocks). We propose SyntenyMapper, a novel tool for refining predefined syntenic regions. SyntenyMapper creates a set of blocks with conserved gene order between two genomes and finds all minor rearrangements that occurred since the evolutionary split of the two species considered. We also present TrackMapper, a SyntenyMapper-based tool that allows users to directly compare genome features, such as histone modifications, between two organisms, and identify genes with highly conserved features. We demonstrate SyntenyMapper's advantages by conducting a large-scale analysis of micro-rearrangements within syntenic regions of 25 eukaryotic species. Unsurprisingly, the number and length of syntenic regions is correlated with evolutionary distance, while the number of micro-rearrangements depends only on the size of the harboring region. On the other hand, the size of rearranged regions remains relatively constant regardless of the evolutionary distance between the organisms, implying a length constraint in the rearrangement process. SyntenyMapper is a useful software tool for both large-scale and gene-centric genome comparisons.
RNA synthesis and decay rates determine the steady-state levels of cellular RNAs. Metabolic tagging of newly transcribed RNA by 4-thiouridine (4sU) can reveal the relative contributions of RNA ...synthesis and decay rates. The kinetics of RNA processing, however, had so far remained unresolved. Here, we show that ultrashort 4sU-tagging not only provides snapshot pictures of eukaryotic gene expression but, when combined with progressive 4sU-tagging and RNA-seq, reveals global RNA processing kinetics at nucleotide resolution. Using this method, we identified classes of rapidly and slowly spliced/degraded introns. Interestingly, each class of splicing kinetics was characterized by a distinct association with intron length, gene length, and splice site strength. For a large group of introns, we also observed long lasting retention in the primary transcript, but efficient secondary splicing or degradation at later time points. Finally, we show that processing of most, but not all small nucleolar (sno)RNA-containing introns is remarkably inefficient with the majority of introns being spliced and degraded rather than processed into mature snoRNAs. In summary, our study yields unparalleled insights into the kinetics of RNA processing and provides the tools to study molecular mechanisms of RNA processing and their contribution to the regulation of gene expression.
Any method that de novo predicts protein function should do better than random. More challenging, it also ought to outperform simple homology-based inference.
Here, we describe a few methods that ...predict protein function exclusively through homology. Together, they set the bar or lower limit for future improvements.
During the development of these methods, we faced two surprises. Firstly, our most successful implementation for the baseline ranked very high at CAFA1. In fact, our best combination of homology-based methods fared only slightly worse than the top-of-the-line prediction method from the Jones group. Secondly, although the concept of homology-based inference is simple, this work revealed that the precise details of the implementation are crucial: not only did the methods span from top to bottom performers at CAFA, but also the reasons for these differences were unexpected. In this work, we also propose a new rigorous measure to compare predicted and experimental annotations. It puts more emphasis on the details of protein function than the other measures employed by CAFA and may best reflect the expectations of users. Clearly, the definition of proper goals remains one major objective for CAFA.
Recent improvements in experimental technologies now allow measurements of de novo transcription and/or RNA decay at whole transcriptome level and determination of precise transcript half-lives. Such ...transcript half-lives provide important insights into the regulation of biological processes and the relative contributions of RNA decay and de novo transcription to differential gene expression. In this article, we present HALO (Half-life Organizer), the first software for the precise determination of transcript half-lives from measurements of RNA de novo transcription or decay determined with microarrays or RNA-seq. In addition, methods for quality control, filtering and normalization are supplied. HALO provides a graphical user interface, command-line tools and a well-documented Java application programming interface (API). Thus, it can be used both by biologists to determine transcript half-lives fast and reliably with the provided user interfaces as well as software developers integrating transcript half-life analysis into other gene expression profiling pipelines. Availability: Source code, executables and documentation are available at http://www.bio.ifi.lmu.de/software/halo Contact: caroline.friedel@bio.ifi.lmu.de
The recent advent of conformation capture techniques has provided unprecedented insights into the spatial organization of chromatin. We present a large-scale investigation of the inter-chromosomal ...segment and gene contact networks in embryonic stem cells of two mammalian organisms: humans and mice. Both interaction networks are characterized by a high degree of clustering of genome regions and the existence of hubs. Both genomes exhibit similar structural characteristics such as increased flexibility of certain Y chromosome regions and co-localization of centromere-proximal regions. Spatial proximity is correlated with the functional similarity of genes in both species. We also found a significant association between spatial proximity and the co-expression of genes in the human genome. The structural properties of chromatin are also species specific, including the presence of two highly interactive regions in mouse chromatin and an increased contact density on short, gene-rich human chromosomes, thereby indicating their central nuclear position. Trans-interacting segments are enriched in active marks in human and had no distinct feature profile in mouse. Thus, in contrast to interactions within individual chromosomes, the inter-chromosomal interactions in human and mouse embryonic stem cells do not appear to be conserved.
Provider: - Institution: - Data provided by Europeana Collections- Greifswald, Univ., Diss., 2016- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 ...1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
P-519
The indicated level of significance refers in each case to day 1.
Telemonitoring of BP is feasible in pharmacological studies and allows unbiased evaluation of the extent and onset of action of ...antihypertensive drugs. Further analysis of all BP data will give detailed information on morning/evening ratio of antihypertensive efficacy and onset of action of Olmesartan.
Key Words: Telemonitoring of Blood Pressure, Blood Pressure Self-Measurement, OLMETEL Study
;;2>POSTERS: Risk Factors/Global Assessment
BPSM is increasingly used in pharmacological studies as it provides longitudinal information on the time course of blood pressure (BP) over several days and weeks. Traditional BPSM is however limited ...by reporting bias and data loss. The OLMETEL study investigates the feasibility of BP-telemonitoring in previous uncontrolled hypertensives treated with Olmesartan (Olmetec®, Sankyo Pharma GmbH) over 12 weeks. Telemonitoring was performed with the Tensiophone 2 device (TP2, upper arm oscillometric device, Tensiomed Hungary).TP2 home monitors were programmed through standard phone lines and data were automatically downloaded to the remote service center. 60 patients performed morning and evening BPSM with TP2 over an average of 80 monitoring days (2,53 BP readings/day). More than 12,000 BP values were sucessfully transmitted through standard phone line and are available for statistical analysis. Data from 49 patients over 56 days are presented in the table: Systolic/Diastolic BP Heart Rate day 1 154/88 mmHg 79 beats/min day 7 144/80 mmHg, p < 0,05 78 beats/min, n.s. day 28 143/80 mmHg, p < 0,05 76 beats/min, n.s. day 56 140/79 mmHg, p < 0,005 76 beats/min, n.s. The indicated level of significance refers in each case to day 1. Telemonitoring of BP is feasible in pharmacological studies and allows unbiased evaluation of the extent and onset of action of antihypertensive drugs. Further analysis of all BP data will give detailed information on morning/evening ratio of antihypertensive efficacy and onset of action of Olmesartan.
Provider: - Institution: - Data provided by Europeana Collections- München, Technische Universität München, Diss., 2015- All metadata published by Europeana are available free of restriction under ...the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
PDF
