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Background
The computational prediction of DNA methylation has become an important topic in the recent years due to its role in the epigenetic control of normal and cancer-related processes. While previous prediction approaches focused merely on differences between methylated and unmethylated DNA sequences, recent experimental results have shown the presence of much more complex patterns of methylation across tissues and time in the human genome. These patterns are only partially described by a binary model of DNA methylation. In this work we propose a novel approach, based on profile analysis of tissue-specific methylation that uncovers significant differences in the sequences of CpG islands (CGIs) that predispose them to a tissue- specific methylation pattern.Results
We defined CGI methylation profiles that separate not only between constitutively methylated and unmethylated CGIs, but also identify CGIs showing a differential degree of methylation across tissues and cell-types or a lack of methylation exclusively in sperm. These profiles are clearly distinguished by a number of CGI attributes including their evolutionary conservation, their significance, as well as the evolutionary evidence of prior methylation. Additionally, we assess profile functionality with respect to the different compartments of protein coding genes and their possible use in the prediction of DNA methylation.Conclusion
Our approach provides new insights into the biological features that determine if a CGI has a functional role in the epigenetic control of gene expression and the features associated with CGI methylation susceptibility. Moreover, we show that the ability to predict CGI methylation is based primarily on the quality of the biological information used and the relationships uncovered between different sources of knowledge. The strategy presented here is able to predict, besides the constitutively methylated and unmethylated classes, two more tissue specific methylation classes conserving the accuracy provided by leading binary methylation classification methods. 相似文献3.
Background
Mannose binding proteins (MBPs) play a vital role in several biological functions such as defense mechanisms. These proteins bind to mannose on the surface of a wide range of pathogens and help in eliminating these pathogens from our body. Thus, it is important to identify mannose interacting residues (MIRs) in order to understand mechanism of recognition of pathogens by MBPs.Results
This paper describes modules developed for predicting MIRs in a protein. Support vector machine (SVM) based models have been developed on 120 mannose binding protein chains, where no two chains have more than 25% sequence similarity. SVM models were developed on two types of datasets: 1) main dataset consists of 1029 mannose interacting and 1029 non-interacting residues, 2) realistic dataset consists of 1029 mannose interacting and 10320 non-interacting residues. In this study, firstly, we developed standard modules using binary and PSSM profile of patterns and got maximum MCC around 0.32. Secondly, we developed SVM modules using composition profile of patterns and achieved maximum MCC around 0.74 with accuracy 86.64% on main dataset. Thirdly, we developed a model on a realistic dataset and achieved maximum MCC of 0.62 with accuracy 93.08%. Based on this study, a standalone program and web server have been developed for predicting mannose interacting residues in proteins (http://www.imtech.res.in/raghava/premier/).Conclusions
Compositional analysis of mannose interacting and non-interacting residues shows that certain types of residues are preferred in mannose interaction. It was also observed that residues around mannose interacting residues have a preference for certain types of residues. Composition of patterns/peptide/segment has been used for predicting MIRs and achieved reasonable high accuracy. It is possible that this novel strategy may be effective to predict other types of interacting residues. This study will be useful in annotating the function of protein as well as in understanding the role of mannose in the immune system. 相似文献4.
The recognition of gene/protein names in literature is one of the pivotal steps in the processing of biological literatures for information extraction
or data mining. We have compiled a lexicon of biomedical words (conserved patterns/ potential motifs) which has the combination of only 20
alphabets of amino acids. The remaining 6 letters of the English alphabets (B, J, O, U, X, Z) are treated as invalid amino acid characters (to our
context), We have jumbled the 6 letters for the sake of usage and convenience and termed as ’JUZBOX‘ and these characters were filtered in the
biomedical lexicon. Undoubtedly, the generation of biomedical words from protein sequence using JUZBOX have applications specific for
functional annotation.
Availability
JUZBOX is available freely at http://www.spices.res.in/juzbox 相似文献5.
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Deus HF Stanislaus R Veiga DF Behrens C Wistuba II Minna JD Garner HR Swisher SG Roth JA Correa AM Broom B Coombes K Chang A Vogel LH Almeida JS 《PloS one》2008,3(8):e2946
Background
Data, data everywhere. The diversity and magnitude of the data generated in the Life Sciences defies automated articulation among complementary efforts. The additional need in this field for managing property and access permissions compounds the difficulty very significantly. This is particularly the case when the integration involves multiple domains and disciplines, even more so when it includes clinical and high throughput molecular data.Methodology/Principal Findings
The emergence of Semantic Web technologies brings the promise of meaningful interoperation between data and analysis resources. In this report we identify a core model for biomedical Knowledge Engineering applications and demonstrate how this new technology can be used to weave a management model where multiple intertwined data structures can be hosted and managed by multiple authorities in a distributed management infrastructure. Specifically, the demonstration is performed by linking data sources associated with the Lung Cancer SPORE awarded to The University of Texas MDAnderson Cancer Center at Houston and the Southwestern Medical Center at Dallas. A software prototype, available with open source at www.s3db.org, was developed and its proposed design has been made publicly available as an open source instrument for shared, distributed data management.Conclusions/Significance
The Semantic Web technologies have the potential to addresses the need for distributed and evolvable representations that are critical for systems Biology and translational biomedical research. As this technology is incorporated into application development we can expect that both general purpose productivity software and domain specific software installed on our personal computers will become increasingly integrated with the relevant remote resources. In this scenario, the acquisition of a new dataset should automatically trigger the delegation of its analysis. 相似文献8.
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Edward G. Hawkins Ian Martin Lindsay M. Kondo Meredith E. Judy Victoria E. Brings Chung-Lung Chan GinaMari G. Blackwell Jill C. Bettinger Andrew G. Davies 《Genetics》2015,199(1):135-149
The Prp43 DExD/H-box protein is required for progression of the biochemically distinct pre-messenger RNA and ribosomal RNA (rRNA) maturation pathways. In Saccharomyces cerevisiae, the Spp382/Ntr1, Sqs1/Pfa1, and Pxr1/Gno1 proteins are implicated as cofactors necessary for Prp43 helicase activation during spliceosome dissociation (Spp382) and rRNA processing (Sqs1 and Pxr1). While otherwise dissimilar in primary sequence, these Prp43-binding proteins each contain a short glycine-rich G-patch motif required for function and thought to act in protein or nucleic acid recognition. Here yeast two-hybrid, domain-swap, and site-directed mutagenesis approaches are used to investigate G-patch domain activity and portability. Our results reveal that the Spp382, Sqs1, and Pxr1 G-patches differ in Prp43 two-hybrid response and in the ability to reconstitute the Spp382 and Pxr1 RNA processing factors. G-patch protein reconstitution did not correlate with the apparent strength of the Prp43 two-hybrid response, suggesting that this domain has function beyond that of a Prp43 tether. Indeed, while critical for Pxr1 activity, the Pxr1 G-patch appears to contribute little to the yeast two-hybrid interaction. Conversely, deletion of the primary Prp43 binding site within Pxr1 (amino acids 102–149) does not impede rRNA processing but affects small nucleolar RNA (snoRNA) biogenesis, resulting in the accumulation of slightly extended forms of select snoRNAs, a phenotype unexpectedly shared by the prp43 loss-of-function mutant. These and related observations reveal differences in how the Spp382, Sqs1, and Pxr1 proteins interact with Prp43 and provide evidence linking G-patch identity with pathway-specific DExD/H-box helicase activity. 相似文献
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Background
Epigenome-wide association scans (EWAS) are an increasingly powerful and widely-used approach to assess the role of epigenetic variation in human complex traits. However, this rapidly emerging field lacks dedicated visualisation tools that can display features specific to epigenetic datasets.Result
We developed coMET, an R package and online tool for visualisation of EWAS results in a genomic region of interest. coMET generates a regional plot of epigenetic-phenotype association results and the estimated DNA methylation correlation between CpG sites (co-methylation), with further options to visualise genomic annotations based on ENCODE data, gene tracks, reference CpG-sites, and user-defined features. The tool can be used to display phenotype association signals and correlation patterns of microarray or sequencing-based DNA methylation data, such as Illumina Infinium 450k, WGBS, or MeDIP-seq, as well as other types of genomic data, such as gene expression profiles. The software is available as a user-friendly online tool from http://epigen.kcl.ac.uk/cometand as an R Bioconductor package. Source code, examples, and full documentation are also available from GitHub.Conclusion
Our new software allows visualisation of EWAS results with functional genomic annotations and with estimation of co-methylation patterns. coMET is available to a wide audience as an online tool and R package, and can be a valuable resource to interpret results in the fast growing field of epigenetics. The software is designed for epigenetic data, but can also be applied to genomic and functional genomic datasets in any species. 相似文献11.
Background
Male-factor infertility is a common condition, and etiology is unknown for a high proportion of cases. Abnormal epigenetic programming of the germline is proposed as a possible mechanism compromising spermatogenesis of some men currently diagnosed with idiopathic infertility. During germ cell maturation and gametogenesis, cells of the germ line undergo extensive epigenetic reprogramming. This process involves widespread erasure of somatic-like patterns of DNA methylation followed by establishment of sex-specific patterns by de novo DNA methylation. Incomplete reprogramming of the male germ line could, in theory, result in both altered sperm DNA methylation and compromised spermatogenesis.Methodology/Principal Finding
We determined concentration, motility and morphology of sperm in semen samples collected by male members of couples attending an infertility clinic. Using MethyLight and Illumina assays we measured methylation of DNA isolated from purified sperm from the same samples. Methylation at numerous sequences was elevated in DNA from poor quality sperm.Conclusions
This is the first report of a broad epigenetic defect associated with abnormal semen parameters. Our results suggest that the underlying mechanism for these epigenetic changes may be improper erasure of DNA methylation during epigenetic reprogramming of the male germ line. 相似文献12.
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Tom Baden Andre Maia Chagas Greg Gage Timothy Marzullo Lucia L. Prieto-Godino Thomas Euler 《PLoS biology》2015,13(3)
The introduction of affordable, consumer-oriented 3-D printers is a milestone in the current “maker movement,” which has been heralded as the next industrial revolution. Combined with free and open sharing of detailed design blueprints and accessible development tools, rapid prototypes of complex products can now be assembled in one’s own garage—a game-changer reminiscent of the early days of personal computing. At the same time, 3-D printing has also allowed the scientific and engineering community to build the “little things” that help a lab get up and running much faster and easier than ever before.Applications of 3-D printing technologies (Fig. 1A, Box 1) have become as diverse as the types of materials that can be used for printing. Replacement parts at the International Space Station may be printed in orbit from durable plastics or metals, while back on Earth the food industry is starting to explore the same basic technology to fold strings of chocolate into custom-shaped confectionary. Also, consumer-oriented laser-cutting technology makes it very easy to cut raw materials such as sheets of plywood, acrylic, or aluminum into complex shapes within seconds. The range of possibilities comes to light when those mechanical parts are combined with off-the-shelf electronics, low-cost microcontrollers like Arduino boards [1], and single-board computers such as a Beagleboard [2] or a Raspberry Pi [3]. After an initial investment of typically less than a thousand dollars (e.g., to set-up a 3-D printer), the only other materials needed to build virtually anything include a few hundred grams of plastic (approximately US$30/kg), cables, and basic electronic components [4,5].Open in a separate windowFig 1Examples of open 3-D printed laboratory tools.
A
1, Components for laboratory tools, such as the base for a micromanipulator [18] shown here, can be rapidly prototyped using 3-D printing. A
2, The printed parts can be easily combined with an off-the-shelf continuous rotation servo-motor (bottom) to motorize the main axis. B
1, A 3-D printable micropipette [8], designed in OpenSCAD [19], shown in full (left) and cross-section (right). B
2, The pipette consists of the printed parts (blue), two biro fillings with the spring, an off-the-shelf piece of tubing to fit the tip, and one screw used as a spacer. B
3, Assembly is complete with a laboratory glove or balloon spanned between the two main printed parts and sealed with tape to create an airtight bottom chamber continuous with the pipette tip. Accuracy is ±2–10 μl depending on printer precision, and total capacity of the system is easily adjusted using two variables listed in the source code, or accessed via the “Customizer” plugin on the thingiverse link [8]. See also the first table.Area Project Source Microscopy Smartphone Microscope
http://www.instructables.com/id/10-Smartphone-to-digital-microscope-conversion
iPad Microscope
http://www.thingiverse.com/thing:31632
Raspberry Pi Microscope
http://www.thingiverse.com/thing:385308
Foldscope
http://www.foldscope.com/
Molecular Biology Thermocycler (PCR)
http://openpcr.org/
Water bath
http://blog.labfab.cc/?p=47
Centrifuge
http://www.thingiverse.com/thing:151406
Dremelfuge
http://www.thingiverse.com/thing:1483
Colorometer
http://www.thingiverse.com/thing:73910
Micropipette
http://www.thingiverse.com/thing:255519
Gel Comb
http://www.thingiverse.com/thing:352873
Hot Plate
http://www.instructables.com/id/Programmable-Temperature-Controller-Hot-Plate/
Magnetic Stirrer
http://www.instructables.com/id/How-to-Build-a-Magnetic-Stirrer/
Electrophysiology Waveform Generator
http://www.instructables.com/id/Arduino-Waveform-Generator/
Open EEG
https://www.olimex.com/Products/EEG/OpenEEG/
Mobile ECG
http://mobilecg.hu/
Extracellular amplifier
https://backyardbrains.com/products/spikerBox
Micromanipulator
http://www.thingiverse.com/thing:239105
Open Ephys
http://open-ephys.org/
Other Syringe pump
http://www.thingiverse.com/thing:210756
Translational Stage
http://www.thingiverse.com/thing:144838
Vacuum pump
http://www.instructables.com/id/The-simplest-vacuum-pump-in-the-world/
Skinner Box
http://www.kscottz.com/open-skinner-box-pycon-2014/