Allocation Costs Associated with Induced Defense in Phaeocystis globosa (Prymnesiophyceae): the Effects of Nutrient Availability

在球形棕囊藻诱导防御相关的配置成本(Prymnesiophyceae):养分有效性的影响

Colony enlargement in Phaeocystis globosa has been considered as an induced defense strategy that reduces its susceptibility to grazers, but allocation costs inflicted by this plastic morphological defense are poorly understood. We conducted experiments in which P. globosa cultures were exposed to chemical cues from copepods, ciliates and heterotrophic dinoflagellates, respectively, under nutrient sufficient and deficient conditions to evaluate allocation costs associated with induced defense. Phaeocystis globosa responded to chemical cues from grazers by increasing colony diameter irrespective of nutrient conditions. We did not find trade-offs between induced defense and growth rate under nutrient sufficient conditions. Instead, induced defensive P. globosa had higher growth rates than non-induced P. globosa. When nutrient became limited, P. globosa exposed to grazing cues from copepods and dinoflagellates had significantly decreased growth rates when compared with non-induced P. globosa. We suggested that the decreased growth revealed allocation costs associated with induced defense that may influence on the trophic interactions between Phaeocystis and consumers.

[详细]

  • Scientific Reports 5
  • 10年前
  • Article

Pattern formation in multiplex networks

在多元化的网络模式的形成

The advances in understanding complex networks have generated increasing interest in dynamical processes occurring on them. Pattern formation in activator-inhibitor systems has been studied in networks, revealing differences from the classical continuous media. Here we study pattern formation in a new framework, namely multiplex networks. These are systems where activator and inhibitor species occupy separate nodes in different layers. Species react across layers but diffuse only within their own layer of distinct network topology. This multiplicity generates heterogeneous patterns with significant differences from those observed in single-layer networks. Remarkably, diffusion-induced instability can occur even if the two species have the same mobility rates; condition which can never destabilize single-layer networks. The instability condition is revealed using perturbation theory and expressed by a combination of degrees in the different layers. Our theory demonstrates that the existence of such topology-driven instabilities is generic in multiplex networks, providing a new mechanism of pattern formation.

[详细]

  • Scientific Reports 5
  • 10年前
  • Article

All-nanophotonic NEMS biosensor on a chip

芯片上的所有生物传感器的纳米光子器件

Integrated chemical and biological sensors give advantages in cost, size and weight reduction and open new prospects for parallel monitoring and analysis. Biosensors based on nanoelectromechanical systems (NEMS) are the most attractive candidates for the integrated platform. However, actuation and transduction techniques (e.g. electrostatic, magnetomotive, thermal or piezoelectric) limit their operation to laboratory conditions. All-optical approach gives the possibility to overcome this problem, nevertheless, the existing schemes are either fundamentally macroscopic or excessively complicated and expensive in mass production. Here we propose a novel scheme of extremely compact NEMS biosensor monolithically integrated on a chip with all-nanophotonic transduction and actuation. It consists of the nanophotonic waveguide and the nanobeam cantilever placed above the waveguide, both fabricated in the same CMOS-compatible process. Being in the near field of the strongly confined photonic or plasmonic mode, cantilever is efficiently actuated and its response is directly read out using the same waveguide, which results in a very high sensitivity and capability of single-molecule detection even in atmosphere.

[详细]

  • Scientific Reports 5
  • 10年前
  • Article

Structural ensembles reveal intrinsic disorder for the multi-stimuli responsive bio-mimetic protein Rec1-resilin

结构集成揭示内在的障碍多重刺激响应性的仿生蛋白REC1肢弹性

Rec1-resilin is the first recombinant resilin-mimetic protein polymer, synthesized from exon-1 of the Drosophila melanogaster gene CG15920 that has demonstrated unusual multi-stimuli responsiveness in aqueous solution. Crosslinked hydrogels of Rec1-resilin have also displayed remarkable mechanical properties including near-perfect rubber-like elasticity. The structural basis of these extraordinary properties is not clearly understood. Here we combine a computational and experimental investigation to examine structural ensembles of Rec1-resilin in aqueous solution. The structure of Rec1-resilin in aqueous solutions is investigated experimentally using circular dichroism (CD) spectroscopy and small angle X-ray scattering (SAXS). Both bench-top and synchrotron SAXS are employed to extract structural data sets of Rec1-resilin and to confirm their validity. Computational approaches have been applied to these experimental data sets in order to extract quantitative information about structural ensembles including radius of gyration, pair-distance distribution function, and the fractal dimension. The present work confirms that Rec1-resilin is an intrinsically disordered protein (IDP) that displays equilibrium structural qualities between those of a structured globular protein and a denatured protein. The ensemble optimization method (EOM) analysis reveals a single conformational population with partial compactness. This work provides new insight into the structural ensembles of Rec1-resilin in solution.

[详细]

  • Scientific Reports 5
  • 10年前
  • Article

Single prokaryotic cell isolation and total transcript amplification protocol for transcriptomic analysis

单核细胞分离和全转录扩增转录组分析

This protocol enables amplification of the total transcript of a single prokaryotic cell for in-depth analysis. Laser-capture microdissection is used to isolate single cells, and amplified cDNA can be further analyzed by microarray.

[详细]

  • Nature Protocols 10, 974 (2015)
  • 10年前
  • Protocol

Uncovering distinct protein-network topologies in heterogeneous cell populations

发现异质性细胞群中不同的蛋白质网络的拓扑结构

Background: Cell biology research is fundamentally limited by the number of intracellular components, particularly proteins, that can be co-measured in the same cell. Therefore, cell-to-cell heterogeneity in unmeasured proteins can lead to completely different observed relations between the same measured proteins. Attempts to infer such relations in a heterogeneous cell population can yield uninformative average relations if only one underlying biochemical network is assumed. To address this, we developed a method that recursively couples an iterative unmixing process with a Bayesian analysis of each unmixed subpopulation. Results: Our approach enables to identify the number of distinct cell subpopulations, unmix their corresponding observations and resolve the network structure of each subpopulation. Using simulations of the MAPK pathway upon EGF and NGF stimulations we assess the performance of the method. We demonstrate that the presented method can identify better than clustering approaches the number of subpopulations within a mixture of observations, thus resolving correctly the statistical relations between the proteins. Conclusions: Coupling the unmixing of multiplexed observations with the inference of statistical relations between the measured parameters is essential for the success of both of these processes. Here we present a conceptual and algorithmic solution to achieve such coupling and hence to analyze data obtained from a natural mixture of cell populations. As the technologies and necessity for multiplexed measurements are rising in the systems biology era, this work addresses an important current challenge in the analysis of the derived data.

[详细]

  • BMC Systems Biology 2015, null:24
  • 10年前

UNCLES: method for the identification of genes differentially consistently co-expressed in a specific subset of datasets

叔叔:对基因的识别差异始终有限数据集的特定子集表示方法

Background: Collective analysis of the increasingly emerging gene expression datasets are required. The recently proposed binarisation of consensus partition matrices (Bi-CoPaM) method can combine clustering results from multiple datasets to identify the subsets of genes which are consistently co-expressed in all of the provided datasets in a tuneable manner. However, results validation and parameter setting are issues that complicate the design of such methods. Moreover, although it is a common practice to test methods by application to synthetic datasets, the mathematical models used to synthesise such datasets are usually based on approximations which may not always be sufficiently representative of real datasets. Results: Here, we propose an unsupervised method for the unification of clustering results from multiple datasets using external specifications (UNCLES). This method has the ability to identify the subsets of genes consistently co-expressed in a subset of datasets while being poorly co-expressed in another subset of datasets, and to identify the subsets of genes consistently co-expressed in all given datasets. We also propose the M-N scatter plots validation technique and adopt it to set the parameters of UNCLES, such as the number of clusters, automatically. Additionally, we propose an approach for the synthesis of gene expression datasets using real data profiles in a way which combines the ground-truth-knowledge of synthetic data and the realistic expression values of real data, and therefore overcomes the problem of faithfulness of synthetic expression data modelling. By application to those datasets, we validate UNCLES while comparing it with other conventional clustering methods, and of particular relevance, biclustering methods. We further validate UNCLES by application to a set of 14 real genome-wide yeast datasets as it produces focused clusters that conform well to known biological facts. Furthermore, in-silico-based hypotheses regarding the function of a few previously unknown genes in those focused clusters are drawn. Conclusions: The UNCLES method, the M-N scatter plots technique, and the expression data synthesis approach will have wide application for the comprehensive analysis of genomic and other sources of multiple complex biological datasets. Moreover, the derived in-silico-based biological hypotheses represent subjects for future functional studies.

[详细]

  • BMC Bioinformatics 2015, null:184
  • 10年前

Mitonuclear Ecology

线粒体核生态学

Eukaryotes were born of a chimeric union between two prokaryotes—the progenitors of the mitochondrial and nuclear genomes. Early in eukaryote evolution, most mitochondrial genes were lost or transferred to the nucleus, but a core set of genes that code exclusively for products associated with the electron transport system remained in the mitochondrion. The products of these mitochondrial genes work in intimate association with the products of nuclear genes to enable oxidative phosphorylation and core energy production. The need for coadaptation, the challenge of cotransmission, and the possibility of genomic conflict between mitochondrial and nuclear genes have profound consequences for the ecology and evolution of eukaryotic life. An emerging interdisciplinary field that I call "mitonuclear ecology" is reassessing core concepts in evolutionary ecology including sexual reproduction, two sexes, sexual selection, adaptation, and speciation in light of the interactions of mitochondrial and nuclear genomes.

[详细]

  • Molecular Biology and Evolution
  • 10年前
  • Review

Whole Genome Sequencing Investigation of a Tuberculosis Outbreak in Port-au-Prince, Haiti Caused by a Strain with a “Low-Level” rpoB Mutation L511P – Insights into a Mechanism of Resistance Escalation

全基因组测序在太子港的结核病疫情调查,造成海地的一株“低水平”l511p rpoB基因突变–了解耐药机制ESCA

by Oksana Ocheretina, Lishuang Shen, Vincent E. Escuyer, Marie-Marcelle Mabou, Gertrude Royal-Mardi, Sean E. Collins, Jean W. Pape, Daniel W. Fitzgerald

The World Health Organization recommends diagnosing Multidrug-Resistant Tuberculosis (MDR-TB) in high burden countries by detection of mutations in Rifampin (RIF) Resistance Determining Region of Mycobacterium tuberculosis rpoB gene with rapid molecular tests GeneXpert MTB/RIF and Hain MTBDRplus. Such mutations are found in >95% of Mycobacterium tuberculosis strains resistant to RIF by conventional culture-based drug susceptibility testing (DST). However routine diagnostic screening with molecular tests uncovered specific “low level” rpoB mutations conferring resistance to RIF below the critical concentration of 1 μg/ml in some phenotypically susceptible strains. Cases with discrepant phenotypic (susceptible) and genotypic (resistant) results for resistance to RIF account for at least 10% of resistant diagnoses by molecular tests and urgently require new guidelines to inform therapeutic decision making. Eight strains with a “low level” rpoB mutation L511P were isolated by GHESKIO laboratory between 2008 and 2012 from 6 HIV-negative and 2 HIV-positive patients during routine molecular testing. Five isolates with a single L511P mutation and two isolates with double mutation L511P&M515T had MICs for RIF between 0.125 and 0.5 μg/ml and tested susceptible in culture-based DST. The eighth isolate carried a double mutation L511P&D516C and was phenotypically resistant to RIF. All eight strains shared the same spoligotype SIT 53 commonly found in Haiti but classic epidemiological investigation failed to uncover direct contacts between the patients. Whole Genome Sequencing (WGS) revealed that L511P cluster isolates resulted from a clonal expansion of an ancestral strain resistant to Isoniazid and to a very low level of RIF. Under the selective pressure of RIF-based therapy the strain acquired mutation in the M306 codon of embB followed by secondary mutations in rpoB and escalation of resistance level. This scenario highlights the importance of subcritical resistance to RIF for both clinical management of patients and public health and provides support for introducing rpoB mutations as proxy for MICs into laboratory diagnosis of RIF resistance. This study illustrates that WGS is a promising multi-purpose genotyping tool for high-burden settings as it provides both “gold standard” sequencing results for prediction of drug susceptibility and a high-resolution data for epidemiological investigation in a single assay.

[详细]

  • PloS one
  • 10年前

A Single-Nucleotide Polymorphism in an Endo-1,4-β-Glucanase Gene Controls Seed Coat Permeability in Soybean

单核苷酸多态性在一个内切-1,4 -β-葡聚糖酶基因控制大豆种皮的通透性

by Seong-Jin Jang, Masako Sato, Kei Sato, Yutaka Jitsuyama, Kaien Fujino, Haruhide Mori, Ryoji Takahashi, Eduardo R. Benitez, Baohui Liu, Tetsuya Yamada, Jun Abe

Physical dormancy, a structural feature of the seed coat known as hard seededness, is an important characteristic for adaptation of plants against unstable and unpredictable environments. To dissect the molecular basis of qHS1, a quantitative trait locus for hard seededness in soybean (Glycine max (L) Merr.), we developed a near-isogenic line (NIL) of a permeable (soft-seeded) cultivar, Tachinagaha, containing a hard-seed allele from wild soybean (G. soja) introduced by successive backcrossings. The hard-seed allele made the seed coat of Tachinagaha more rigid by increasing the amount of β-1,4-glucans in the outer layer of palisade cells of the seed coat on the dorsal side of seeds, known to be a point of entrance of water. Fine-mapping and subsequent expression and sequencing analyses revealed that qHS1 encodes an endo-1,4-β-glucanase. A single-nucleotide polymorphism (SNP) introduced an amino acid substitution in a substrate-binding cleft of the enzyme, possibly reducing or eliminating its affinity for substrates in permeable cultivars. Introduction of the genomic region of qHS1 from the impermeable (hard-seeded) NIL into the permeable cultivar Kariyutaka resulted in accumulation of β-1,4-glucan in the outer layer of palisade cells and production of hard seeds. The SNP allele found in the NIL was further associated with the occurrence of hard seeds in soybean cultivars of various origins. The findings of this and previous studies may indicate that qHS1 is involved in the accumulation of β-1,4-glucan derivatives such as xyloglucan and/or β-(1,3)(1,4)-glucan that reinforce the impermeability of seed coats in soybean.

[详细]

  • PloS one
  • 10年前

Genomic Comparison of the Closely-Related Salmonella enterica Serovars Enteritidis, Dublin and Gallinarum

密切相关的沙门氏菌血清型沙门氏菌的基因组比较,都柏林和鸡

by T. David Matthews, Robert Schmieder, Genivaldo G. Z. Silva, Julia Busch, Noriko Cassman, Bas E. Dutilh, Dawn Green, Brian Matlock, Brian Heffernan, Gary J. Olsen, Leigh Farris Hanna, Dieter M. Schifferli, Stanley Maloy, Elizabeth A. Dinsdale, Robert A. Edwards

The Salmonella enterica serovars Enteritidis, Dublin, and Gallinarum are closely related but differ in virulence and host range. To identify the genetic elements responsible for these differences and to better understand how these serovars are evolving, we sequenced the genomes of Enteritidis strain LK5 and Dublin strain SARB12 and compared these genomes to the publicly available Enteritidis P125109, Dublin CT 02021853 and Dublin SD3246 genome sequences. We also compared the publicly available Gallinarum genome sequences from biotype Gallinarum 287/91 and Pullorum RKS5078. Using bioinformatic approaches, we identified single nucleotide polymorphisms, insertions, deletions, and differences in prophage and pseudogene content between strains belonging to the same serovar. Through our analysis we also identified several prophage cargo genes and pseudogenes that affect virulence and may contribute to a host-specific, systemic lifestyle. These results strongly argue that the Enteritidis, Dublin and Gallinarum serovars of Salmonella enterica evolve by acquiring new genes through horizontal gene transfer, followed by the formation of pseudogenes. The loss of genes necessary for a gastrointestinal lifestyle ultimately leads to a systemic lifestyle and niche exclusion in the host-specific serovars.

[详细]

  • PloS one
  • 10年前

Computational identification of novel microRNAs and their targets in the malarial vector, Anopheles stephensi.

计算的新型小分子核糖核酸及其目标识别疟疾向量,按蚊stephensi。

MicroRNAs are a ~22 nucleotide small non-coding RNAs found in animals, plants and viruses. They regulate key cellular processes by enhancing, degrading or silencing protein coding targets. Currently most of the data on miRNA is available from Drosophila . Given their important post-transcriptional role in several organisms, there is a need to understand the miRNA mediated processes in normal and abnormal conditions. Here we report four novel microRNAs ast - mir - 2502, ast - mir - 2559, ast - mir - 3868 and ast - mir - 9891 in Anopheles stephensi identified from a set of 3,052 transcriptome sequences, showing average minimum free energy of -31.8 kcal/mol of duplex formation with mRNA indicating their functional relevance. Phylogenetic study shows conservation of sequence signatures within the Class Insecta. Furthermore, 26 potential targets of these four miRNAs have been predicted that play an important role in the mosquito life-cycle. This work leads to novel leads and experimental possibilities for improved understanding of gene regulatory processes in mosquito.

[详细]

  • Syst Synth Biol. 2015 Jun;9(1-2):11-7
  • 10年前
  • Syst Synth Biol

Regulation of a phenylalanine ammonia lyase (BbPAL) by calmodulin in response to environmental changes in the entomopathogenic fungus Beauveria bassiana.

监管的苯丙氨酸氨裂解酶(BbPAL)钙调蛋白在昆虫病原真菌白僵菌的环境变化。

Phenylalanine ammonia lyase (PAL, E.C. 4.3.1.5) catalyzes the deamination of L -phenylalanine to trans-cinnamic acid and ammonia, facilitating a critical step in the phenylpropanoid pathway that produces a variety of secondary metabolites. In this study, we isolated BbPAL gene in the entomopathogenic fungus Beauveria bassiana. According to multiple sequence alignment, homology modeling, and in vitro PAL activity, we demonstrated that BbPAL acts as a typical PAL enzyme in B. bassiana. BbPAL interacted with calmodulin (CaM) in vitro and in vivo, indicating that BbPAL is a novel CaM-binding protein. The functional role of CaM in BbPAL action was to negatively regulate the BbPAL activity in B. bassiana. HPLC analysis revealed that L -phenylalanine was reduced and trans-cinnamic acid was increased in response to the CaM inhibitor W-7. Dark conditions suppressed BbPAL activity in B. bassiana, compared to light. In addition, heat and cold stresses inhibited BbPAL activity in B. bassiana. Interestingly, these negative effects of BbPAL activity by dark, heat, and cold conditions were recovered by W-7 treatment, suggesting that the inhibitory mechanism is mediated through stimulation of CaM activity. Therefore, this work suggests that BbPAL plays a role in the phenylpropanoid pathway mediated by environmental stimuli via the CaM signaling pathway.

[详细]

  • Environ Microbiol. 2015 May 13;
  • 10年前
  • Environ Microbiol

Transcriptional control of fungal cell cycle and cellular events by Fkh2, a forkhead transcription factor in an insect pathogen.

转录控制真菌的细胞周期和细胞活动由Fkh2 forkhead转录因子在昆虫病原体。

Transcriptional control of the cell cycle by forkhead (Fkh) transcription factors is likely associated with fungal adaptation to host and environment. Here we show that Fkh2, an ortholog of yeast Fkh1/2, orchestrates cell cycle and many cellular events of Beauveria bassiana, a filamentous fungal insect pathogen. Deletion of Fkh2 in B. bassiana resulted in dramatic down-regulation of the cyclin-B gene cluster and hence altered cell cycle (longer G2/M and S, but shorter G0/G1, phases) in unicellular blastospores. Consequently, ΔFkh2 produced twice as many, but smaller, blastospores than wild-type under submerged conditions, and formed denser septa and shorter/broader cells in aberrantly branched hyphae. In these hyphae, clustered genes required for septation and conidiation were remarkedly up-regulated, followed by higher yield and slower germination of aerial conidia. Moreover, ΔFkh2 displayed attenuated virulence and decreased tolerance to chemical and environmental stresses, accompanied with altered transcripts and activities of phenotype-influencing proteins or enzymes. All the changes in ΔFkh2 were restored by Fkh2 complementation. All together, Fkh2-dependent transcriptional control is vital for the adaptation of B. bassiana to diverse habitats of host insects and hence contributes to its biological control potential against arthropod pests.

[详细]

  • Sci Rep. 2015;5:10108
  • 10年前
  • Sci Rep

Metabolomics reveals insect metabolic responses associated with fungal infection.

代谢组学揭示昆虫代谢反应与真菌感染有关。

The interactions between insects and pathogenic fungi are complex. We employed metabolomic techniques to profile insect metabolic dynamics upon infection by the pathogenic fungus Beauveria bassiana. Silkworm larvae were infected with fungal spores and microscopic observations demonstrated that the exhaustion of insect hemocytes was coupled with fungal propagation in the insect body cavity. Metabolomic analyses revealed that fungal infection could significantly alter insect energy and nutrient metabolisms as well as the immune defense responses, including the upregulation of carbohydrates, amino acids, fatty acids, and lipids, but the downregulation of eicosanoids and amines. The insect antifeedant effect of the fungal infection was evident with the reduced level of maclurin (a component of mulberry leaves) in infected insects but elevated accumulations in control insects. Insecticidal and cytotoxic mycotoxins like oosporein and beauveriolides were also detected in insects at the later stages of infection. Taken together, the metabolomics data suggest that insect immune responses are energy-cost reactions and the strategies of nutrient deprivation, inhibition of host immune responses, and toxin production would be jointly employed by the fungus to kill insects. The data obtained in this study will facilitate future functional studies of genes and pathways associated with insect-fungus interactions.

[详细]

  • Anal Bioanal Chem. 2015 Jun;407(16):4815-21
  • 10年前
  • Anal Bioanal Chem

Molecular characterization of a novel amalgavirus from the entomopathogenic fungus Beauveria bassiana.

分子特征的小说amalgavirus昆虫病原真菌白僵菌。

Beauveria bassiana is a ubiquitous entomopathogen infecting hundreds of insect species. We have determined the genomic organization and the complete nucleotide sequence of a novel virus isolated from the isolate A24 of B. bassiana. Phylogenetic analysis of the polymerase gene reveals that the virus, tentatively named Beauveria bassiana virus 1, belongs to the family Amalgaviridae and represents a distinct lineage of amalgaviruses infecting fungi.

[详细]

  • Arch Virol. 2015 Jun;160(6):1585-8
  • 10年前
  • Arch Virol

Partitioning between recoding and termination at a stop codon-selenocysteine insertion sequence

在记录和终止在一个终止密码子的硒代半胱氨酸插入序列划分

Selenocysteine (Sec) is inserted into proteins by recoding a UGA stop codon followed by a selenocysteine insertion sequence (SECIS). UGA recoding by the Sec machinery is believed to be very inefficient owing to RF2-mediated termination at UGA. Here we show that recoding efficiency in vivo is 30–40% independently of the cell growth rate. Efficient recoding requires sufficient selenium concentrations in the medium. RF2 is an unexpectedly poor competitor of Sec. We recapitulate the major characteristics of SECIS-dependent UGA recoding in vitro using a fragment of fdhF-mRNA encoding a natural bacterial selenoprotein. Only 40% of actively translating ribosomes that reach the UGA codon insert Sec, even in the absence of RF2, suggesting that the capacity to insert Sec into proteins is inherently limited. RF2 does not compete with the Sec incorporation machinery; rather, it terminates translation on those ribosomes that failed to incorporate Sec. The data suggest a model in which early recruitment of Sec-tRNASec–SelB–GTP to the SECIS blocks the access of RF2 to the stop codon, thereby prioritizing recoding over termination at Sec-dedicated stop codons.

[详细]

  • Nucleic Acids Research
  • 10年前
  • Molecular Biology

Sequence-independent characterization of viruses based on the pattern of viral small RNAs produced by the host

基于病毒小RNA由主机产生的模式病毒序列独立的表征

Virus surveillance in vector insects is potentially of great benefit to public health. Large-scale sequencing of small and long RNAs has previously been used to detect viruses, but without any formal comparison of different strategies. Furthermore, the identification of viral sequences largely depends on similarity searches against reference databases. Here, we developed a sequence-independent strategy based on virus-derived small RNAs produced by the host response, such as the RNA interference pathway. In insects, we compared sequences of small and long RNAs, demonstrating that viral sequences are enriched in the small RNA fraction. We also noted that the small RNA size profile is a unique signature for each virus and can be used to identify novel viral sequences without known relatives in reference databases. Using this strategy, we characterized six novel viruses in the viromes of laboratory fruit flies and wild populations of two insect vectors: mosquitoes and sandflies. We also show that the small RNA profile could be used to infer viral tropism for ovaries among other aspects of virus biology. Additionally, our results suggest that virus detection utilizing small RNAs can also be applied to vertebrates, although not as efficiently as to plants and insects.

[详细]

  • Nucleic Acids Research
  • 10年前
  • Computational Biology

Characterization of fusion genes and the significantly expressed fusion isoforms in breast cancer by hybrid sequencing

融合基因及其表达明显的融合的异构体在乳腺癌的杂交测序

We developed an innovative hybrid sequencing approach, IDP-fusion, to detect fusion genes, determine fusion sites and identify and quantify fusion isoforms. IDP-fusion is the first method to study gene fusion events by integrating Third Generation Sequencing long reads and Second Generation Sequencing short reads. We applied IDP-fusion to PacBio data and Illumina data from the MCF-7 breast cancer cells. Compared with the existing tools, IDP-fusion detects fusion genes at higher precision and a very low false positive rate. The results show that IDP-fusion will be useful for unraveling the complexity of multiple fusion splices and fusion isoforms within tumorigenesis-relevant fusion genes.

[详细]

  • Nucleic Acids Research
  • 10年前
  • Methods Online

SNiPlay3: a web-based application for exploration and large scale analyses of genomic variations

sniplay3:一个基于Web的应用程序开发的基因组规模大的变化分析

SNiPlay is a web-based tool for detection, management and analysis of genetic variants including both single nucleotide polymorphisms (SNPs) and InDels. Version 3 now extends functionalities in order to easily manage and exploit SNPs derived from next generation sequencing technologies, such as GBS (genotyping by sequencing), WGRS (whole gre-sequencing) and RNA-Seq technologies. Based on the standard VCF (variant call format) format, the application offers an intuitive interface for filtering and comparing polymorphisms using user-defined sets of individuals and then establishing a reliable genotyping data matrix for further analyses. Namely, in addition to the various scaled-up analyses allowed by the application (genomic annotation of SNP, diversity analysis, haplotype reconstruction and network, linkage disequilibrium), SNiPlay3 proposes new modules for GWAS (genome-wide association studies), population stratification, distance tree analysis and visualization of SNP density. Additionally, we developed a suite of Galaxy wrappers for each step of the SNiPlay3 process, so that the complete pipeline can also be deployed on a Galaxy instance using the Galaxy ToolShed procedure and then be computed as a Galaxy workflow. SNiPlay is accessible at http://sniplay.southgreen.fr.

[详细]

  • Nucleic Acids Research
  • 10年前
  • Web Server issue

Context-specific role of SOX9 in NF-Y mediated gene regulation in colorectal cancer cells

在病毒Sox9上下文特定的作用介导的基因调控大肠癌细胞

Roles for SOX9 have been extensively studied in development and particular emphasis has been placed on SOX9 roles in cell lineage determination in a number of discrete tissues. Aberrant expression of SOX9 in many cancers, including colorectal cancer, suggests roles in these diseases as well and recent studies have suggested tissue- and context-specific roles of SOX9. Our genome wide approach by chromatin immunoprecipitation sequencing (ChIP-seq) in human colorectal cancer cells identified a number of physiological targets of SOX9, including ubiquitously expressed cell cycle regulatory genes, such as CCNB1 and CCNB2, CDK1, and TOP2A. These novel high affinity-SOX9 binding peaks precisely overlapped with binding sites for histone-fold NF-Y transcription factor. Furthermore, our data showed that SOX9 is recruited by NF-Y to these promoters of cell cycle regulatory genes and that SOX9 is critical for the full function of NF-Y in activation of the cell cycle genes. Mutagenesis analysis and in vitro binding assays provided additional evidence to show that SOX9 affinity is through NF-Y and that SOX9 DNA binding domain is not necessary for SOX9 affinity to those target genes. Collectively, our results reveal possibly a context-dependent, non-classical regulatory role for SOX9.

[详细]

  • Nucleic Acids Research
  • 10年前
  • Gene regulation, Chromatin and Epigenetics

TiQuant: Software for tissue analysis, quantification and surface reconstruction

tiquant:组织分析软件,定量和表面重建

Motivation: TiQuant is a modular software tool for efficient quantification of biological tissues based on volume data obtained by biomedical image modalities. It includes a number of versatile image and volume processing chains tailored to the analysis of different tissue types which have been experimentally verified. TiQuant implements a novel method for the reconstruction of three-dimensional surfaces of biological systems, data that often cannot be obtained experimentally but which is of utmost importance for tissue modelling in systems biology.

Availability: TiQuant is freely available for non-commercial use at msysbio.com/tiquant. Windows, OSX and Linux are supported.

Contact: hoehme@uni-leipzig.de

Supplementary information: Supplementary data are available at Bioinformatics online.

[详细]

  • Bioinformatics
  • 10年前
  • APPLICATIONS NOTE

Assembling Short Reads from Jumping Libraries with Large Insert Sizes

组装短读取跳图书馆插入大尺寸

Motivation: Advances in NGS technologies and sample preparation recently enabled generation of high-quality jumping libraries that have a potential to significantly improve short read assemblies. However, assembly algorithms have to catch up with experimental innovations in order to benefit from them and to produce high-quality assemblies.

Results: We present a new algorithm that extends recently described exSPAnder universal repeat resolution approach to enable its applications to several challenging data types, including jumping libraries generated by the recently developed Illumina Nextera Mate Pair protocol. We demonstrate that, with these improvements, bacterial genomes often can be assembled in a few contigs using only a single Nextera Mate Pair library of short reads.

Availability and implementation: Described algorithms are implemented in C++ as a part of SPAdes genome assembler, which is freely available at bioinf.spbau.ru/en/spades.

Keywords: genome assembly, scaffolding, repeat resolution, jumping libraries, Nextera Mate Pairs.

Contact: ap@bioinf.spbau.ru

Supplementary material: To be posted on-line.

[详细]

  • Bioinformatics
  • 10年前
  • ORIGINAL PAPER