Optimal Assembly for High Throughput Shotgun Sequencing

We present a framework for the design of optimal assembly algorithms for shotgun sequencing under the criterion of complete reconstruction. We derive a lower bound on the read length and the coverage depth required for reconstruction in terms of the repeat statistics of the genome. Building on earlier works, we design a de Brujin graph based assembly algorithm which can achieve very close to the lower bound for repeat statistics of a wide range of sequenced genomes, including the GAGE datasets. The results are based on a set of necessary and sufficient conditions on the DNA sequence and the reads for reconstruction. The conditions can be viewed as the shotgun sequencing analogue of Ukkonen-Pevzner's necessary and sufficient conditions for Sequencing by Hybridization.Comment: 26 pages, 18 figure

Telescoper: de novo assembly of highly repetitive regions.

MotivationWith advances in sequencing technology, it has become faster and cheaper to obtain short-read data from which to assemble genomes. Although there has been considerable progress in the field of genome assembly, producing high-quality de novo assemblies from short-reads remains challenging, primarily because of the complex repeat structures found in the genomes of most higher organisms. The telomeric regions of many genomes are particularly difficult to assemble, though much could be gained from the study of these regions, as their evolution has not been fully characterized and they have been linked to aging.ResultsIn this article, we tackle the problem of assembling highly repetitive regions by developing a novel algorithm that iteratively extends long paths through a series of read-overlap graphs and evaluates them based on a statistical framework. Our algorithm, Telescoper, uses short- and long-insert libraries in an integrated way throughout the assembly process. Results on real and simulated data demonstrate that our approach can effectively resolve much of the complex repeat structures found in the telomeres of yeast genomes, especially when longer long-insert libraries are used.AvailabilityTelescoper is publicly available for download at sourceforge.net/p/[email protected] informationSupplementary data are available at Bioinformatics online

Novel Fabrication Routes to Nickel-based Cermet Electrodes for Solid Oxide Cells

Solid oxide cells (SOCs) are promising energy conversion devices in which the chemical energy of fuels is converted into electrical energy in an efficient manner. It is generally accepted that electrode microstructure plays an important role in determining the performance and durability of SOCs. The electrode is required to contain large amount of active reaction sites, termed triple phase boundaries (TPBs), to promote the electrochemical reaction. At the same time, effective transport pathways need to be established to and from each TPB. Therefore, the microstructure-performance relationships need to be understood in order to develop highly efficient electrodes. In this study a novel electrode, prepared by infiltration of nickel nano-particles into Gadolinium doped Ceria porous scaffold, is proposed. The research aims to understand the fundamental phenomena underpinning SOC operation for steam electrolysis/H2 oxidation in these electrodes and to establish the relationship between the microstructure of the infiltrated electrode and electrode performance. The electronic conductivity of infiltrated electrodes was tested by the van der Pauw method over the temperature range 20-700 ˚C. Electrochemical behaviour was assessed for fuel cell and electrolysis modes using three electrode AC and DC measurements. The microstructure was studied by SEM and FIB techniques, including 3-D imaging and quantification. Ultimately, this is to allow electrodes to be designed with desired characteristics. In addition, a novel approach for electrode preparation by Selective Laser Sintering (SLS) was evaluated by conducting a proof of concept study. This fabrication technique enables the porosity and pattern of the electrode to be controlled by regulating the parameters of the laser (laser power and laser speed). The feasibility of using this novel technique for solid oxide cells was demonstrated. A method for the fabrication of high performance ‘electrodes by design’ through the combination of the two techniques in which the scaffold preparation by SLS is followed by infiltration is in prospect.Open Acces

Inferring the Sign of Kinase-Substrate Interactions by Combining Quantitative Phosphoproteomics with a Literature-Based Mammalian Kinome Network

Protein phosphorylation is a reversible post-translational modification commonly used by cell signaling networks to transmit information about the extracellular environment into intracellular organelles for the regulation of the activity and sorting of proteins within the cell. For this study we reconstructed a literature-based mammalian kinase-substrate network from several online resources. The interactions within this directed graph network connect kinases to their substrates, through specific phosphosites including kinase-kinase regulatory interactions. However, the "signs" of links, activation or inhibition of the substrate upon phosphorylation, within this network are mostly unknown. Here we show how we can infer the "signs" indirectly using data from quantitative phosphoproteomics experiments applied to mammalian cells combined with the literature-based kinase-substrate network. Our inference method was able to predict the sign for 321 links and 153 phosphosites on 120 kinases, resulting in signed and directed subnetwork of mammalian kinase-kinase interactions. Such an approach can rapidly advance the reconstruction of cell signaling pathways and networks regulating mammalian cells.Comment: 5 page, 3 figures, IEEE-BIBE confrenc

How does mobility shape parental strategies:a case of the Israeli global middle class and their 'immobile' peers in Tel Aviv

We examined the parental strategies of global middle class (GMC) parents currently living in Israel, and compared these to their local middle class (LMC) peers. Both groups of parents were focused on securing advantages for their children through education choices and practices of cultivation. The central difference between these two groups of middle class parents was the ways in which ‘mobile-mindedness’ was conceived of, and in turn shaped the future aspirations they held for their children. A second critical finding was that this group of GMC actively fostered strong relations to belonging to their ‘home’ nation, challenging the suggestion of rootless nomads found in the literature. We argue that the GMCs in our sample think locally in each place they settle in order to secure the educational advantage, but act globally with respect to their children’s prospective futures. Meanwhile, the LMCs think globally in terms of cultivating forms of capital to secure advantages for their children, but do so with a locally-informed frame of reference for their imagined futures. These conceptual insights into the lived narratives of the GMC have implications for the ways we come to understand this emerging middle class fraction, and should shape further research in this area

Genes2WordCloud: a quick way to identify biological themes from gene lists and free text

<p>Abstract</p> <p>Background</p> <p>Word-clouds recently emerged on the web as a solution for quickly summarizing text by maximizing the display of most relevant terms about a specific topic in the minimum amount of space. As biologists are faced with the daunting amount of new research data commonly presented in textual formats, word-clouds can be used to summarize and represent biological and/or biomedical content for various applications.</p> <p>Results</p> <p>Genes2WordCloud is a web application that enables users to quickly identify biological themes from gene lists and research relevant text by constructing and displaying word-clouds. It provides users with several different options and ideas for the sources that can be used to generate a word-cloud. Different options for rendering and coloring the word-clouds give users the flexibility to quickly generate customized word-clouds of their choice.</p> <p>Methods</p> <p>Genes2WordCloud is a word-cloud generator and a word-cloud viewer that is based on WordCram implemented using Java, Processing, AJAX, mySQL, and PHP. Text is fetched from several sources and then processed to extract the most relevant terms with their computed weights based on word frequencies. Genes2WordCloud is freely available for use online; it is open source software and is available for installation on any web-site along with supporting documentation at <url>http://www.maayanlab.net/G2W</url>.</p> <p>Conclusions</p> <p>Genes2WordCloud provides a useful way to summarize and visualize large amounts of textual biological data or to find biological themes from several different sources. The open source availability of the software enables users to implement customized word-clouds on their own web-sites and desktop applications.</p

Genes2Networks: connecting lists of gene symbols using mammalian protein interactions databases

<p>Abstract</p> <p>Background</p> <p>In recent years, mammalian protein-protein interaction network databases have been developed. The interactions in these databases are either extracted manually from low-throughput experimental biomedical research literature, extracted automatically from literature using techniques such as natural language processing (NLP), generated experimentally using high-throughput methods such as yeast-2-hybrid screens, or interactions are predicted using an assortment of computational approaches. Genes or proteins identified as significantly changing in proteomic experiments, or identified as susceptibility disease genes in genomic studies, can be placed in the context of protein interaction networks in order to assign these genes and proteins to pathways and protein complexes.</p> <p>Results</p> <p>Genes2Networks is a software system that integrates the content of ten mammalian interaction network datasets. Filtering techniques to prune low-confidence interactions were implemented. Genes2Networks is delivered as a web-based service using AJAX. The system can be used to extract relevant subnetworks created from "seed" lists of human Entrez gene symbols. The output includes a dynamic linkable three color web-based network map, with a statistical analysis report that identifies significant intermediate nodes used to connect the seed list.</p> <p>Conclusion</p> <p>Genes2Networks is powerful web-based software that can help experimental biologists to interpret lists of genes and proteins such as those commonly produced through genomic and proteomic experiments, as well as lists of genes and proteins associated with disease processes. This system can be used to find relationships between genes and proteins from seed lists, and predict additional genes or proteins that may play key roles in common pathways or protein complexes.</p

SMaSH: A Benchmarking Toolkit for Human Genome Variant Calling

Motivation: Computational methods are essential to extract actionable information from raw sequencing data, and to thus fulfill the promise of next-generation sequencing technology. Unfortunately, computational tools developed to call variants from human sequencing data disagree on many of their predictions, and current methods to evaluate accuracy and computational performance are ad-hoc and incomplete. Agreement on benchmarking variant calling methods would stimulate development of genomic processing tools and facilitate communication among researchers. Results: We propose SMaSH, a benchmarking methodology for evaluating human genome variant calling algorithms. We generate synthetic datasets, organize and interpret a wide range of existing benchmarking data for real genomes, and propose a set of accuracy and computational performance metrics for evaluating variant calling methods on this benchmarking data. Moreover, we illustrate the utility of SMaSH to evaluate the performance of some leading single nucleotide polymorphism (SNP), indel, and structural variant calling algorithms. Availability: We provide free and open access online to the SMaSH toolkit, along with detailed documentation, at smash.cs.berkeley.edu