Aberrant time to most recent common ancestor as a signature of natural selection

异常时间最近的共同祖先的自然选择的签名

Natural selection inference methods often target one mode of selection of a particular age and strength. However, detecting multiple modes simultaneously, or with atypical representations, would be advantageous for understanding a population’s evolutionary history. We have developed an anomaly detection algorithm using distributions of pairwise time to most recent common ancestor (TMRCA) to simultaneously detect multiple modes of natural selection in whole-genome sequences. Since natural selection distorts local genealogies in distinct ways, the method uses pairwise TMRCA distributions, which approximate genealogies at a non-recombining locus, to detect distortions without targeting a specific mode of selection. We evaluate the performance of our method, TSel, for both positive and balancing selection over different time-scales and selection strengths and compare TSel’s performance to that of other methods. We then apply TSel to the Complete Genomics diversity panel, a set of human whole-genome sequences, and recover loci previously inferred to be under positive or balancing selection.

[详细]

  • Molecular Biology and Evolution
  • 5年前
  • Research Article

Pathway-Dependent Effectiveness of Network Algorithms for Gene Prioritization

基因排序网络算法的路径依赖性

by Jung Eun Shim, Sohyun Hwang, Insuk Lee

A network-based approach has proven useful for the identification of novel genes associated with complex phenotypes, including human diseases. Because network-based gene prioritization algorithms are based on propagating information of known phenotype-associated genes through networks, the pathway structure of each phenotype might significantly affect the effectiveness of algorithms. We systematically compared two popular network algorithms with distinct mechanisms – direct neighborhood which propagates information to only direct network neighbors, and network diffusion which diffuses information throughout the entire network – in prioritization of genes for worm and human phenotypes. Previous studies reported that network diffusion generally outperforms direct neighborhood for human diseases. Although prioritization power is generally measured for all ranked genes, only the top candidates are significant for subsequent functional analysis. We found that high prioritizing power of a network algorithm for all genes cannot guarantee successful prioritization of top ranked candidates for a given phenotype. Indeed, the majority of the phenotypes that were more efficiently prioritized by network diffusion showed higher prioritizing power for top candidates by direct neighborhood. We also found that connectivity among pathway genes for each phenotype largely determines which network algorithm is more effective, suggesting that the network algorithm used for each phenotype should be chosen with consideration of pathway gene connectivity.

[详细]

  • PloS one
  • 5年前

Asian Citrus Psyllid Expression Profiles Suggest Candidatus Liberibacter Asiaticus-Mediated Alteration of Adult Nutrition and Metabolism, and of Nymphal Development and Immunity

亚洲柑橘木虱的表达谱表明柑橘黄龙病菌介导的成人营养及代谢的变化,和若虫发育和免疫

by Meenal Vyas, Tonja W. Fisher, Ruifeng He, William Nelson, Guohua Yin, Joseph M. Cicero, Mark Willer, Ryan Kim, Robin Kramer, Greg A. May, John A. Crow, Carol A. Soderlund, David R. Gang, Judith K. Brown

The Asian citrus psyllid (ACP) Diaphorina citri Kuwayama (Hemiptera: Psyllidae) is the insect vector of the fastidious bacterium Candidatus Liberibacter asiaticus (CLas), the causal agent of citrus greening disease, or Huanglongbing (HLB). The widespread invasiveness of the psyllid vector and HLB in citrus trees worldwide has underscored the need for non-traditional approaches to manage the disease. One tenable solution is through the deployment of RNA interference technology to silence protein-protein interactions essential for ACP-mediated CLas invasion and transmission. To identify psyllid interactor-bacterial effector combinations associated with psyllid-CLas interactions, cDNA libraries were constructed from CLas-infected and CLas-free ACP adults and nymphs, and analyzed for differential expression. Library assemblies comprised 24,039,255 reads and yielded 45,976 consensus contigs. They were annotated (UniProt), classified using Gene Ontology, and subjected to in silico expression analyses using the Transcriptome Computational Workbench (TCW) (http://www.sohomoptera.org/ACPPoP/). Functional-biological pathway interpretations were carried out using the Kyoto Encyclopedia of Genes and Genomes databases. Differentially expressed contigs in adults and/or nymphs represented genes and/or metabolic/pathogenesis pathways involved in adhesion, biofilm formation, development-related, immunity, nutrition, stress, and virulence. Notably, contigs involved in gene silencing and transposon-related responses were documented in a psyllid for the first time. This is the first comparative transcriptomic analysis of ACP adults and nymphs infected and uninfected with CLas. The results provide key initial insights into host-parasite interactions involving CLas effectors that contribute to invasion-virulence, and to host nutritional exploitation and immune-related responses that appear to be essential for successful ACP-mediated circulative, propagative CLas transmission.

[详细]

  • PloS one
  • 5年前

Avoiding the Enumeration of Infeasible Elementary Flux Modes by Including Transcriptional Regulatory Rules in the Enumeration Process Saves Computational Costs

避免不可行的基元模式的枚举的枚举过程的转录调控规则节省计算成本

by Christian Jungreuthmayer, David E. Ruckerbauer, Matthias P. Gerstl, Michael Hanscho, Jürgen Zanghellini

Despite the significant progress made in recent years, the computation of the complete set of elementary flux modes of large or even genome-scale metabolic networks is still impossible. We introduce a novel approach to speed up the calculation of elementary flux modes by including transcriptional regulatory information into the analysis of metabolic networks. Taking into account gene regulation dramatically reduces the solution space and allows the presented algorithm to constantly eliminate biologically infeasible modes at an early stage of the computation procedure. Thereby, computational costs, such as runtime, memory usage, and disk space, are extremely reduced. Moreover, we show that the application of transcriptional rules identifies non-trivial system-wide effects on metabolism. Using the presented algorithm pushes the size of metabolic networks that can be studied by elementary flux modes to new and much higher limits without the loss of predictive quality. This makes unbiased, system-wide predictions in large scale metabolic networks possible without resorting to any optimization principle.

[详细]

  • PloS one
  • 5年前

Exonic Re-Sequencing of the Chromosome 2q24.3 Parkinson’s Disease Locus

外显子的染色体2q24.3帕金森病基因测序

by Catherine Labbé, Kotaro Ogaki, Oswaldo Lorenzo-Betancor, Minerva M. Carrasquillo, Michael G. Heckman, Allan McCarthy, Alexandra I. Soto-Ortolaza, Ronald L. Walton, Timothy Lynch, Joanna Siuda, Grzegorz Opala, Anna Krygowska-Wajs, Maria Barcikowska, Krzysztof Czyzewski, Dennis W. Dickson, Ryan J. Uitti, Zbigniew K. Wszolek, Owen A. Ross

Genome-wide association studies (GWAS) in Parkinson’s disease (PD) have identified over 20 genomic regions associated with disease risk. Many of these loci include several candidate genes making it difficult to pinpoint the causal gene. The locus on chromosome 2q24.3 encompasses three genes: B3GALT1, STK39, and CERS6. In order to identify if the causal variants are simple missense changes, we sequenced all 31 exons of these three genes in 187 patients with PD. We identified 13 exonic variants including four non-synonymous and three insertion/deletion variants (indels). These non-synonymous variants and rs2102808, the GWAS tag SNP, were genotyped in three independent series consisting of a total of 1976 patients and 1596 controls. Our results show that the seven identified 2q24.3 coding variants are not independently responsible for the GWAS association signal at the locus; however, there is a haplotype, which contains both rs2102808 and a STK39 exon 1 6bp indel variant, that is significantly associated with PD risk (Odds Ratio [OR] = 1.35, 95% CI: 1.11–1.64, P = 0.003). This haplotype is more associated than each of the two variants independently (OR = 1.23, P = 0.005 and 1.10, P = 0.10, respectively). Our findings suggest that the risk variant is likely located in a non-coding region. Additional sequencing of the locus including promoter and regulatory regions will be needed to pinpoint the association at this locus that leads to an increased risk to PD.

[详细]

  • PloS one
  • 5年前

Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk

在细胞内转运基因与上皮性卵巢癌(EOC)的常见遗传变异风险

by Ganna Chornokur, Hui-Yi Lin, Jonathan P. Tyrer, Kate Lawrenson, Joe Dennis, Ernest K. Amankwah, Xiaotao Qu, Ya-Yu Tsai, Heather S. L. Jim, Zhihua Chen, Ann Y. Chen, Jennifer Permuth-Wey, Katja KH. Aben, Hoda Anton-Culver, Natalia Antonenkova, Fiona Bruinsma, Elisa V. Bandera, Yukie T. Bean, Matthias W. Beckmann, Maria Bisogna, Line Bjorge, Natalia Bogdanova, Louise A. Brinton, Angela Brooks-Wilson, Clareann H. Bunker, Ralf Butzow, Ian G. Campbell, Karen Carty, Jenny Chang-Claude, Linda S. Cook, Daniel W. Cramer, Julie M. Cunningham, Cezary Cybulski, Agnieszka Dansonka-Mieszkowska, Andreas du Bois, Evelyn Despierre, Ed Dicks, Jennifer A. Doherty, Thilo Dörk, Matthias Dürst, Douglas F. Easton, Diana M. Eccles, Robert P. Edwards, Arif B. Ekici, Peter A. Fasching, Brooke L. Fridley, Yu-Tang Gao, Aleksandra Gentry-Maharaj, Graham G. Giles, Rosalind Glasspool, Marc T. Goodman, Jacek Gronwald, Patricia Harrington, Philipp Harter, Alexander Hein, Florian Heitz, Michelle A. T. Hildebrandt, Peter Hillemanns, Claus K. Hogdall, Estrid Hogdall, Satoyo Hosono, Anna Jakubowska, Allan Jensen, Bu-Tian Ji, Beth Y. Karlan, Linda E. Kelemen, Mellissa Kellar, Lambertus A. Kiemeney, Camilla Krakstad, Susanne K. Kjaer, Jolanta Kupryjanczyk, Diether Lambrechts, Sandrina Lambrechts, Nhu D. Le, Alice W. Lee, Shashi Lele, Arto Leminen, Jenny Lester, Douglas A. Levine, Dong Liang, Boon Kiong Lim, Jolanta Lissowska, Karen Lu, Jan Lubinski, Lene Lundvall, Leon F. A. G. Massuger, Keitaro Matsuo, Valerie McGuire, John R. McLaughlin, Iain McNeish, Usha Menon, Roger L. Milne, Francesmary Modugno, Kirsten B. Moysich, Roberta B. Ness, Heli Nevanlinna, Ursula Eilber, Kunle Odunsi, Sara H. Olson, Irene Orlow, Sandra Orsulic, Rachel Palmieri Weber, James Paul, Celeste L. Pearce, Tanja Pejovic, Liisa M. Pelttari, Malcolm C. Pike, Elizabeth M. Poole, Harvey A. Risch, Barry Rosen, Mary Anne Rossing, Joseph H. Rothstein, Anja Rudolph, Ingo B. Runnebaum, Iwona K. Rzepecka, Helga B. Salvesen, Eva Schernhammer, Ira Schwaab, Xiao-Ou Shu, Yurii B. Shvetsov, Nadeem Siddiqui, Weiva Sieh, Honglin Song, Melissa C. Southey, Beata Spiewankiewicz, Lara Sucheston, Soo-Hwang Teo, Kathryn L. Terry, Pamela J. Thompson, Lotte Thomsen, Ingvild L. Tangen, Shelley S. Tworoger, Anne M. van Altena, Robert A. Vierkant, Ignace Vergote, Christine S. Walsh, Shan Wang-Gohrke, Nicolas Wentzensen, Alice S. Whittemore, Kristine G. Wicklund, Lynne R. Wilkens, Anna H. Wu, Xifeng Wu, Yin-Ling Woo, Hannah Yang, Wei Zheng, Argyrios Ziogas, Hanis N. Hasmad, Andrew Berchuck, Georgia Chenevix-Trench on behalf of the AOCS management group , Edwin S. Iversen, Joellen M. Schildkraut, Susan J. Ramus, Ellen L. Goode, Alvaro N. A. Monteiro, Simon A. Gayther, Steven A. Narod, Paul D. P. Pharoah, Thomas A. Sellers, Catherine M. Phelan

Background

Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk.

Methods

In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons.

Results

The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4).

Conclusion

These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.

[详细]

  • PloS one
  • 5年前

Characterization of the Maize Chitinase Genes and Their Effect on Aspergillus flavus and Aflatoxin Accumulation Resistance

玉米几丁质酶基因的鉴定及其对黄曲霉和黄曲霉毒素的积累性效应

by Leigh K. Hawkins, J. Erik Mylroie, Dafne A. Oliveira, J. Spencer Smith, Seval Ozkan, Gary L. Windham, W. Paul Williams, Marilyn L. Warburton

Maize (Zea mays L.) is a crop of global importance, but prone to contamination by aflatoxins produced by fungi in the genus Aspergillus. The development of resistant germplasm and the identification of genes contributing to resistance would aid in the reduction of the problem with a minimal need for intervention by farmers. Chitinolytic enzymes respond to attack by potential pathogens and have been demonstrated to increase insect and fungal resistance in plants. Here, all chitinase genes in the maize genome were characterized via sequence diversity and expression patterns. Recent evolution within this gene family was noted. Markers from within each gene were developed and used to map the phenotypic effect on resistance of each gene in up to four QTL mapping populations and one association panel. Seven chitinase genes were identified that had alleles associated with increased resistance to aflatoxin accumulation and A. flavus infection in field grown maize. The chitinase in bin 1.05 identified a new and highly significant QTL, while chitinase genes in bins 2.04 and 5.03 fell directly beneath the peaks of previously published QTL. The expression patterns of these genes corroborate possible grain resistance mechanisms. Markers from within the gene sequences or very closely linked to them are presented to aid in the use of marker assisted selection to improve this trait.

[详细]

  • PloS one
  • 5年前

Ruminal Transcriptomic Analysis of Grass-Fed and Grain-Fed Angus Beef Cattle

喂草和谷物喂养的安古斯肉牛瘤胃的转录组分析

by Yaokun Li, José A. Carrillo, Yi Ding, YangHua He, Chunping Zhao, Linsen Zan, Jiuzhou Song

Beef represents a major diet component and one of the major sources of protein in human. The beef industry in the United States is currently undergoing changes and is facing increased demands especially for natural grass-fed beef. The grass-fed beef obtained their nutrients directly from pastures, which contained limited assimilable energy but abundant amount of fiber. On the contrary, the grain-fed steers received a grain-based regime that served as an efficient source of high-digestible energy. Lately, ruminant animals have been accused to be a substantial contributor for the green house effect. Therefore, the concerns from environmentalism, animal welfare and public health have driven consumers to choose grass-fed beef. Rumen is one of the key workshops to digest forage constituting a critical step to supply enough nutrients for animals’ growth and production. We hypothesize that rumen may function differently in grass- and grain-fed regimes. The objective of this study was to find the differentially expressed genes in the ruminal wall of grass-fed and grain-fed steers, and then explore the potential biopathways. In this study, the RNA Sequencing (RNA-Seq) method was used to measure the gene expression level in the ruminal wall. The total number of reads per sample ranged from 24,697,373 to 36,714,704. The analysis detected 342 differentially expressed genes between ruminal wall samples of animals raised under different regimens. The Fisher’s exact test performed in the Ingenuity Pathway Analysis (IPA) software found 16 significant molecular networks. Additionally, 13 significantly enriched pathways were identified, most of which were related to cell development and biosynthesis. Our analysis demonstrated that most of the pathways enriched with the differentially expressed genes were related to cell development and biosynthesis. Our results provided valuable insights into the molecular mechanisms resulting in the phenotype difference between grass-fed and grain-fed cattle.

[详细]

  • PloS one
  • 5年前

A Minimal Regulatory Network of Extrinsic and Intrinsic Factors Recovers Observed Patterns of CD4+ T Cell Differentiation and Plasticity

外在和内在因素的一个最小的监管网络恢复的CD4 T细胞的分化和可塑性的观察

by Mariana Esther Martinez-Sanchez, Luis Mendoza, Carlos Villarreal, Elena R. Alvarez-Buylla

CD4+ T cells orchestrate the adaptive immune response in vertebrates. While both experimental and modeling work has been conducted to understand the molecular genetic mechanisms involved in CD4+ T cell responses and fate attainment, the dynamic role of intrinsic (produced by CD4+ T lymphocytes) versus extrinsic (produced by other cells) components remains unclear, and the mechanistic and dynamic understanding of the plastic responses of these cells remains incomplete. In this work, we studied a regulatory network for the core transcription factors involved in CD4+ T cell-fate attainment. We first show that this core is not sufficient to recover common CD4+ T phenotypes. We thus postulate a minimal Boolean regulatory network model derived from a larger and more comprehensive network that is based on experimental data. The minimal network integrates transcriptional regulation, signaling pathways and the micro-environment. This network model recovers reported configurations of most of the characterized cell types (Th0, Th1, Th2, Th17, Tfh, Th9, iTreg, and Foxp3-independent T regulatory cells). This transcriptional-signaling regulatory network is robust and recovers mutant configurations that have been reported experimentally. Additionally, this model recovers many of the plasticity patterns documented for different T CD4+ cell types, as summarized in a cell-fate map. We tested the effects of various micro-environments and transient perturbations on such transitions among CD4+ T cell types. Interestingly, most cell-fate transitions were induced by transient activations, with the opposite behavior associated with transient inhibitions. Finally, we used a novel methodology was used to establish that T-bet, TGF-β and suppressors of cytokine signaling proteins are keys to recovering observed CD4+ T cell plastic responses. In conclusion, the observed CD4+ T cell-types and transition patterns emerge from the feedback between the intrinsic or intracellular regulatory core and the micro-environment. We discuss the broader use of this approach for other plastic systems and possible therapeutic interventions.

[详细]

  • PLOS Computational Biology
  • 5年前

[Report] Endocytic sites mature by continuous bending and remodeling of the clathrin coat

[报告]吞网站成熟的连续弯曲的网格蛋白涂层的重塑

During clathrin-mediated endocytosis (CME), plasma membrane regions are internalized to retrieve extracellular molecules and cell surface components. Whether endocytosis occurs by direct clathrin assembly into curved lattices on the budding vesicle or by initial recruitment to flat membranes and subsequent reshaping has been controversial. To distinguish between these models, we combined fluorescence microscopy and electron tomography to locate endocytic sites and to determine their coat and membrane shapes during invagination. The curvature of the clathrin coat increased, whereas the coated surface area remained nearly constant. Furthermore, clathrin rapidly exchanged at all stages of CME. Thus, coated vesicle budding appears to involve bending of a dynamic preassembled clathrin coat.

[详细]

  • Science
  • 5年前

Hybrid System for Ex Vivo Hemorheological and Hemodynamic Analysis: A Feasibility Study

体外血液流变学和血流动力学分析的混合系统的可行性研究

Precise measurement of biophysical properties is important to understand the relation between these properties and the outbreak of cardiovascular diseases (CVDs). However, a systematic measurement for these biophysical parameters under in vivo conditions is nearly impossible because of complex vessel shape and limited practicality. In vitro measurements can provide more biophysical information, but in vitro exposure changes hemorheological properties. In this study, a hybrid system composed of an ultrasound system and microfluidic device is proposed for monitoring hemorheological and hemodynamic properties under more reasonable experimental conditions. Biophysical properties including RBC aggregation, viscosity, velocity, and pressure of blood flows are simultaneously measured under various conditions to demonstrate the feasibility and performance of this measurement system. The proposed technique is applied to a rat extracorporeal loop which connects the aorta and jugular vein directly. As a result, the proposed system is found to measure biophysical parameters reasonably without blood collection from the rat and provided more detailed information. This hybrid system, combining ultrasound imaging and microfluidic techniques to ex vivo animal models, would be useful for monitoring the variations of biophysical properties induced by chemical agents. It can be used to understand the relation between biophysical parameters and CVDs.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

Generation of inheritable and “transgene clean” targeted genome-modified rice in later generations using the CRISPR/Cas9 system

遗传和转基因水稻在清洁“有针对性的基因组修饰后人利用CRISPR/Cas9系统生成

The CRISPR/Cas9 system is becoming an important genome editing tool for crop breeding. Although it has been demonstrated that target mutations can be transmitted to the next generation, their inheritance pattern has not yet been fully elucidated. Here, we describe the CRISPR/Cas9-mediated genome editing of four different rice genes with the help of online target-design tools. High-frequency mutagenesis and a large percentage of putative biallelic mutations were observed in T0 generations. Nonetheless, our results also indicate that the progeny genotypes of biallelic T0 lines are frequently difficult to predict and that the transmission of mutations largely does not conform to classical genetic laws, which suggests that the mutations in T0 transgenic rice are mainly somatic mutations. Next, we followed the inheritance pattern of T1 plants. Regardless of the presence of the CRISPR/Cas9 transgene, the mutations in T1 lines were stably transmitted to later generations, indicating a standard germline transmission pattern. Off-target effects were also evaluated, and our results indicate that with careful target selection, off-target mutations are rare in CRISPR/Cas9-mediated rice gene editing. Taken together, our results indicate the promising production of inheritable and “transgene clean” targeted genome-modified rice in the T1 generation using the CRISPR/Cas9 system.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

Quantitative assessment of single-cell whole genome amplification methods for detecting copy number variation using hippocampal neurons

拷贝数变异检测海马神经元单细胞全基因组扩增方法的定量评价

Single-cell genomic analysis has grown rapidly in recent years and finds widespread applications in various fields of biology, including cancer biology, development, immunology, pre-implantation genetic diagnosis, and neurobiology. To date, the amplification bias, amplification uniformity and reproducibility of the three major single cell whole genome amplification methods (GenomePlex WGA4, MDA and MALBAC) have not been systematically investigated using mammalian cells. In this study, we amplified genomic DNA from individual hippocampal neurons using three single-cell DNA amplification methods, and sequenced them at shallow depth. We then systematically evaluated the GC-bias, reproducibility, and copy number variations among individual neurons. Our results showed that single-cell genome sequencing results obtained from the MALBAC and WGA4 methods are highly reproducible and have a high success rate. The MALBAC displays significant biases towards high GC content. We then attempted to correct the GC bias issue by developing a bioinformatics pipeline, which allows us to call CNVs in single cell sequencing data, and chromosome level and sub-chromosomal level CNVs among individual neurons can be detected. We also proposed a metric to determine the CNV detection limits. Overall, MALBAC and WGA4 have better performance than MDA in detecting CNVs.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

Evolution of an Enzyme from a Noncatalytic Nucleic Acid Sequence

从一个非催化核酸序列酶的进化

The mechanism by which enzymes arose from both abiotic and biological worlds remains an unsolved natural mystery. We postulate that an enzyme can emerge from any sequence of any functional polymer under permissive evolutionary conditions. To support this premise, we have arbitrarily chosen a 50-nucleotide DNA fragment encoding for the Bos taurus (cattle) albumin mRNA and subjected it to test-tube evolution to derive a catalytic DNA (DNAzyme) with RNA-cleavage activity. After only a few weeks, a DNAzyme with significant catalytic activity has surfaced. Sequence comparison reveals that seven nucleotides are responsible for the conversion of the noncatalytic sequence into the enzyme. Deep sequencing analysis of DNA pools along the evolution trajectory has identified individual mutations as the progressive drivers of the molecular evolution. Our findings demonstrate that an enzyme can indeed arise from a sequence of a functional polymer via permissive molecular evolution, a mechanism that may have been exploited by nature for the creation of the enormous repertoire of enzymes in the biological world today.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

Maximal Holevo Quantity Based on Weak Measurements

基于弱测量的信道数量最大

The Holevo bound is a keystone in many applications of quantum information theory. We propose “ maximal Holevo quantity for weak measurements” as the generalization of the maximal Holevo quantity which is defined by the optimal projective measurements. The scenarios that weak measurements is necessary are that only the weak measurements can be performed because for example the system is macroscopic or that one intentionally tries to do so such that the disturbance on the measured system can be controlled for example in quantum key distribution protocols. We evaluate systematically the maximal Holevo quantity for weak measurements for Bell-diagonal states and find a series of results. Furthermore, we find that weak measurements can be realized by noise and project measurements.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

Transcriptomic and proteomic analysis of pre-diapause and non-diapause eggs of migratory locust, Locusta migratoria L. (Orthoptera: Acridoidea)

前滞育与非滞育卵飞蝗转录组和蛋白质组分析,东亚飞蝗L.(直翅目蝗总科)

Low temperature induces diapause in locusts. However, the physiological processes and initiation mechanism of diapause are not well understood. To understand the molecular basis of diapause, ‘omics’ analyses were performed to examine the differences between diapause and non-diapause eggs at both transcriptional and translational levels. Results indicated that a total of 62,241 mRNAs and 212 proteins were differentially expressed. Among them, 116 transcripts had concurrent transcription and translation profiles. Up-regulated genes related to diapause included glutathiones-S-transferase et al., and down-regulated genes including juvenile hormone esterase-like protein et al. KEGG analysis mapped 7,243 and 99 differentially expressed genes and proteins, to 83 and 25 pathways, respectively. Correlation enriched pathways indicated that there were nine identical pathways related to diapause. Gene Ontology analysis placed these genes and proteins into three categories, and a higher proportion of genes related to metabolism was up-regulated than down-regulated. Furthermore, three up-regulated pathways were linked to cryoprotection. This study demonstrates the applicability of high-throughput omics tools to identify molecules linked to diapause in the locust. In addition, it reveals cellular metabolism in diapause eggs is more active than in non-diapause eggs, and up-regulated enzymes may play roles in cryoprotection and storing energy for diapause and post-diapause stages.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

Complex Learning in Bio-plausible Memristive Networks

在生物合理的忆阻网络复杂学习

The emerging memristor-based neuromorphic engineering promises an efficient computing paradigm. However, the lack of both internal dynamics in the previous feedforward memristive networks and efficient learning algorithms in recurrent networks, fundamentally limits the learning ability of existing systems. In this work, we propose a framework to support complex learning functions by introducing dedicated learning algorithms to a bio-plausible recurrent memristive network with internal dynamics. We fabricate iron oxide memristor-based synapses, with well controllable plasticity and a wide dynamic range of excitatory/inhibitory connection weights, to build the network. To adaptively modify the synaptic weights, the comprehensive recursive least-squares (RLS) learning algorithm is introduced. Based on the proposed framework, the learning of various timing patterns and a complex spatiotemporal pattern of human motor is demonstrated. This work paves a new way to explore the brain-inspired complex learning in neuromorphic systems.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

Single Fluorescence Channel-based Multiplex Detection of Avian Influenza Virus by Quantitative PCR with Intercalating Dye

用嵌入染料荧光定量PCR单通道型禽流感病毒的多重检测

Since its invention in 1985 the polymerase chain reaction (PCR) has become a well-established method for amplification and detection of segments of double-stranded DNA. Incorporation of fluorogenic probe or DNA intercalating dyes (such as SYBR Green) into the PCR mixture allowed real-time reaction monitoring and extraction of quantitative information (qPCR). Probes with different excitation spectra enable multiplex qPCR of several DNA segments using multi-channel optical detection systems. Here we show multiplex qPCR using an economical EvaGreen-based system with single optical channel detection. Previously reported non quantitative multiplex real-time PCR techniques based on intercalating dyes were conducted once the PCR is completed by performing melting curve analysis (MCA). The technique presented in this paper is both qualitative and quantitative as it provides information about the presence of multiple DNA strands as well as the number of starting copies in the tested sample. Besides important internal control, multiplex qPCR also allows detecting concentrations of more than one DNA strand within the same sample. Detection of the avian influenza virus H7N9 by PCR is a well established method. Multiplex qPCR greatly enhances its specificity as it is capable of distinguishing both haemagglutinin (HA) and neuraminidase (NA) genes as well as their ratio.

[详细]

  • Scientific Reports 5
  • 5年前
  • Article

Transcriptome profiling provides new insights into the formation of floral scent in Hedychium coronarium

转录组学的研究提供了新的见解,形成花香在<它>姜花<它>

Background: Hedychium coronarium is a popular ornamental plant in tropical and subtropical regions because its flowers not only possess intense and inviting fragrance but also enjoy elegant shape. The fragrance results from volatile terpenes and benzenoids presented in the floral scent profile. However, in this species, even in monocots, little is known about the underlying molecular mechanism of floral scent production. Results: Using Illumina platform, approximately 81 million high-quality reads were obtained from a pooled cDNA library. The de novo assembly resulted in a transcriptome with 65,591 unigenes, 50.90 % of which were annotated using public databases. Digital gene expression (DGE) profiling analysis revealed 7,796 differential expression genes (DEGs) during petal development. GO term classification and KEGG pathway analysis indicated that the levels of transcripts changed significantly in “metabolic process”, including “terpenoid biosynthetic process”. Through a systematic analysis, 35 and 33 candidate genes might be involved in the biosynthesis of floral volatile terpenes and benzenoids, respectively. Among them, flower-specific HcDXS2A, HcGPPS, HcTPSs, HcCNL and HcBCMT1 might play critical roles in regulating the formation of floral fragrance through DGE profiling coupled with floral volatile profiling analyses. In vitro characterization showed that HcTPS6 was capable of generating β-farnesene as its main product. In the transcriptome, 1,741 transcription factors (TFs) were identified and 474 TFs showed differential expression during petal development. It is supposed that two R2R3-MYBs with flower-specific and developmental expression might be involved in the scent production. Conclusions: The novel transcriptome and DGE profiling provide an important resource for functional genomics studies and give us a dynamic view of biological process during petal development in H. coronarium. These data lay the basis for elucidating the molecular mechanism of floral scent formation and regulation in monocot. The results also provide the opportunities for genetic modification of floral scent profile in Hedychium.

[详细]

  • BMC Genomics 2015, null:470
  • 5年前

Distinctive expansion of gene families associated with plant cell wall degradation, secondary metabolism, and nutrient uptake in the genomes of grapevine trunk pathogens

独特的扩展与植物细胞壁降解相关的基因家族,次生代谢,并在葡萄树干病原体基因组的养分吸收

Background: Trunk diseases threaten the longevity and productivity of grapevines in all viticulture production systems. They are caused by distantly-related fungi that form chronic wood infections. Variation in wood-decay abilities and production of phytotoxic compounds are thought to contribute to their unique disease symptoms. We recently released the draft sequences of Eutypa lata, Neofusicoccum parvum and Togninia minima, causal agents of Eutypa dieback, Botryosphaeria dieback and Esca, respectively. In this work, we first expanded genomic resources to three important trunk pathogens, Diaporthe ampelina, Diplodia seriata, and Phaeomoniella chlamydospora, causal agents of Phomopsis dieback, Botryosphaeria dieback, and Esca, respectively. Then we integrated all currently-available information into a genome-wide comparative study to identify gene families potentially associated with host colonization and disease development. Results: The integration of RNA-seq, comparative and ab initio approaches improved the protein-coding gene prediction in T. minima, whereas shotgun sequencing yielded nearly complete genome drafts of Dia. ampelina, Dip. seriata, and P. chlamydospora. The predicted proteomes of all sequenced trunk pathogens were annotated with a focus on functions likely associated with pathogenesis and virulence, namely (i) wood degradation, (ii) nutrient uptake, and (iii) toxin production. Specific patterns of gene family expansion were described using Computational Analysis of gene Family Evolution, which revealed lineage-specific evolution of distinct mechanisms of virulence, such as specific cell wall oxidative functions and secondary metabolic pathways in N. parvum, Dia. ampelina, and E. lata. Phylogenetically-informed principal component analysis revealed more similar repertoires of expanded functions among species that cause similar symptoms, which in some cases did not reflect phylogenetic relationships, thereby suggesting patterns of convergent evolution. Conclusions: This study describes the repertoires of putative virulence functions in the genomes of ubiquitous grapevine trunk pathogens. Gene families with significantly faster rates of gene gain can now provide a basis for further studies of in planta gene expression, diversity by genome re-sequencing, and targeted reverse genetic approaches. The functional validation of potential virulence factors will lead to a more comprehensive understanding of the mechanisms of pathogenesis and virulence, which ultimately will enable the development of accurate diagnostic tools and effective disease management.

[详细]

  • BMC Genomics 2015, null:469
  • 5年前

IBiSS, a versatile and interactive tool for integrated sequence and 3D structure analysis of large macromolecular complexes

ibiss,集成序列和三维大分子复合物的结构分析通用的交互式工具

Motivation

In the past few years, an increasing number of crystal and cryo electron microscopy (cryo-EM) structures of large macromolecular complexes, such as the ribosome or the RNA polymerase, have become available from various species. These multi-subunit complexes can be difficult to analyse at the level of amino acid sequence in combination with the 3D structural organization of the complex. Therefore, novel tools for simultaneous analysis of structure and sequence information of complex assemblies are required to better understand the basis of molecular mechanisms and their functional implications.

Results

Here, we present a web-based tool, IBiSS (Integrative Biology of Sequences and Structures), which is designed for interactively displaying 3D structures and selected sequences of subunits from large macromolecular complexes thus allowing simultaneous structure-sequence analysis such as conserved residues involved in catalysis or protein-protein interfaces. This tool comprises a Graphic User Interface (GUI) and uses a rapid-access internal database, containing the relevant pre-aligned multiple sequences across all species available and 3D structural information. These annotations are automatically retrieved and updated from UniProt and crystallographic and cryo-EM data available in the Protein Data Bank (PDB) and Electron Microscopy Data Bank (EMDB).

Availability and Implementation

The database contains all currently available structures of ribosomes, RNA polymerases, nucleosomes, proteasome, photosystem I and II complexes. IBiSS is available at http://ibiss.igbmc.fr

Contact:

klaholz@igbmc.fr

[详细]

  • Bioinformatics
  • 5年前
  • ORIGINAL PAPER

Simultaneous live imaging of the transcription and nuclear position of specific genes

同时生活和特定基因的转录核位置成像

The relationship between genome organization and gene expression has recently been established. However, the relationships between spatial organization, dynamics, and transcriptional regulation of the genome remain unknown. In this study, we developed a live-imaging method for simultaneous measurements of the transcriptional activity and nuclear position of endogenous genes, which we termed the ‘Real-time Observation of Localization and EXpression (ROLEX)’ system. We demonstrated that ROLEX is highly specific and does not affect the expression level of the target gene. ROLEX enabled detection of sub-genome-wide mobility changes that depended on the state of Nanog transactivation in embryonic stem cells. We believe that the ROLEX system will become a powerful tool for exploring the relationship between transcription and nuclear dynamics in living cells.

[详细]

  • Nucleic Acids Research
  • 5年前
  • Methods Online

Ionic switch controls the DNA state in phage {lambda}

离子开关控制{λ噬菌体DNA状态}

We have recently found that DNA packaged in phage undergoes a disordering transition triggered by temperature, which results in increased genome mobility. This solid-to-fluid like DNA transition markedly increases the number of infectious particles facilitating infection. However, the structural transition strongly depends on temperature and ionic conditions in the surrounding medium. Using titration microcalorimetry combined with solution X-ray scattering, we mapped both energetic and structural changes associated with transition of the encapsidated -DNA. Packaged DNA needs to reach a critical stress level in order for transition to occur. We varied the stress on DNA in the capsid by changing the temperature, packaged DNA length and ionic conditions. We found striking evidence that the intracapsid DNA transition is ‘switched on’ at the ionic conditions mimicking those in vivo and also at the physiologic temperature of infection at 37°C. This ion regulated on-off switch of packaged DNA mobility in turn affects viral replication. These results suggest a remarkable adaptation of phage to the environment of its host bacteria in the human gut. The metastable DNA state in the capsid provides a new paradigm for the physical evolution of viruses.

[详细]

  • Nucleic Acids Research
  • 5年前
  • Genome Integrity, Repair and Replication

The eIF3 complex of Leishmania--subunit composition and mode of recruitment to different cap-binding complexes

利什曼原虫eIF3复合物——亚基组成和招募方式不同的帽结合复合物

Eukaryotic initiation factor 3 (eIF3) is a multi-protein complex and a key participant in the assembly of the translation initiation machinery. In mammals, eIF3 comprises 13 subunits, most of which are characterized by conserved structural domains. The trypanosomatid eIF3 subunits are poorly conserved. Here, we identify 12 subunits that comprise the Leishmania eIF3 complex (LeishIF3a-l) by combining bioinformatics with affinity purification and mass spectrometry analyses. These results highlight the strong association of LeishIF3 with LeishIF1, LeishIF2 and LeishIF5, suggesting the existence of a multi-factor complex. In trypanosomatids, the translation machinery is tightly regulated in the different life stages of these organisms as part of their adaptation and survival in changing environments. We, therefore, addressed the mechanism by which LeishIF3 is recruited to different mRNA cap-binding complexes. A direct interaction was observed in vitro between the fully assembled LeishIF3 complex and recombinant LeishIF4G3, the canonical scaffolding protein of the cap-binding complex in Leishmania promastigotes. We further highlight a novel interaction between the C-terminus of LeishIF3a and LeishIF4E1, the only cap-binding protein that efficiently binds the cap structure under heat shock conditions, anchoring a complex that is deficient of any MIF4G-based scaffolding subunit.

[详细]

  • Nucleic Acids Research
  • 5年前
  • Gene regulation, Chromatin and Epigenetics