Bioinformatics Group

Madrid, Spain

Bioinformatics Group

Madrid, Spain
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Chen T.,Bioinformatics Group | Chen L.,Hong Kong University of Science and Technology | Ozsu M.T.,University of Waterloo | Xiao N.,National University of Defense Technology
IEEE Transactions on Knowledge and Data Engineering | Year: 2013

Query processing over uncertain data streams, in particular top-k query processing, has become increasingly important due to its wide application in many fields such as sensor network monitoring and internet traffic control. In many real applications, multiple top-k queries are registered in the system. Sharing the results of these queries is a key factor in saving the computation cost and providing real-time response. However, due to the complex semantics of uncertain top-k query processing, it is nontrivial to implement sharing among different top-k queries and few works have addressed the sharing issue. In this paper, we formulate various types of sharing among multiple top-k queries over uncertain data streams based on the frequency upper bound of each top-k query. We present an optimal dynamic programming solution as well as a more efficient (in terms of time and space complexity) greedy algorithm to compute the execution plan of executing queries for saving the computation cost between them. Experiments have demonstrated that the greedy algorithm can find the optimal solution in most cases, and it can almost achieve the same performance (in terms of latency and throughput) as the dynamic programming approach. © 2012 IEEE.

Yokoyama T.,Cancer Institute | Kanno Y.,Cancer Institute | Yamazaki Y.,Cancer Institute | Takahara T.,Cancer Institute | And 2 more authors.
Blood | Year: 2010

Trib1 is a myeloid oncogene that cooperates with Hoxa9 and Meis1. Although the MAPK pathway and C/EBP transcription factors are known to interact with Trib proteins, the mechanisms by which Trib1 contributes to myeloid leukemogenesis remains to be clarified. Here we report that interaction between Trib1 and MEK1 is required for Trib1-induced leukemogenesis. The C-terminal ILLHPWF motif that is well conserved among Trib family proteins is required for MEK1 binding, enhancement of ERK phosphorylation, enhanced self-renewal activity of bone marrow cells and leukemogenic activity by Trib1. The motif is also important for Trib1-induced C/EBPα degradation though interaction between Trib1 and C/EBPα is not necessary. Inhibition of ERK phosphorylation suppressed Trib1-induced C/EBPα degradation, indicating an important role for Trib1/MEK1 interaction. These results suggest that Trib1 may be a key mediator between the RTK-MAPK pathway and the C/EBP transcription factor in myeloid leukemogenesis. © 2010 by The American Society of Hematology.

Moldovan G.-L.,Dana-Farber Cancer Institute | Dejsuphong D.,Dana-Farber Cancer Institute | Petalcorin M.I.R.,Cancer Research UK Research Institute | Hofmann K.,Bioinformatics Group | And 3 more authors.
Molecular Cell | Year: 2012

Inappropriate homologous recombination (HR) causes genomic instability and cancer. In yeast, the UvrD family helicase Srs2 is recruited to sites of DNA replication by SUMO-modified PCNA, where it acts to restrict HR by disassembling toxic RAD51 nucleofilaments. How human cells control recombination at replication forks is unknown. Here, we report that the protein PARI, containing a UvrD-like helicase domain, is a PCNA-interacting partner required for preservation of genome stability in human and DT40 chicken cells. Using cell-based and biochemical assays, we show that PARI restricts unscheduled recombination by interfering with the formation of RAD51-DNA HR structures. Finally, we show that PARI knockdown suppresses the genomic instability of Fanconi Anemia/BRCA pathway-deficient cells. Thus, we propose that PARI is a long sought-after factor that suppresses inappropriate recombination events at mammalian replication forks. © 2012 Elsevier Inc.

Polachi N.,Bharathidasan University | Nagaraja P.,Bioinformatics Group | Subramaniyan B.,Bharathidasan University | Mathan G.,Bharathidasan University
Asian Journal of Pharmaceutical and Clinical Research | Year: 2015

Objective: The aim was to study the inhibitory effect of n-butanol fraction of Butea monosperma floral extracts (NBF-BMFE) against HCT116 cells. Moreover, the drug-likeness properties and in silico evaluation of their active compounds toward glycogen synthase kinase-3β (GSK-3β)/Axin and β-catenin/T-Cell factor-4 (Tcf-4) complex proteins. Methods: The three-dimensional protein structures were incurred from RCSB protein data bank, and their active site amino acids predicted using CASTp server. Similarly, the NBE-BMFE phytochemicals were retrieved from PubChem Database then their absorption, distribution, metabolism, excretion, and toxicity (ADMET)-related descriptors were calculated by using the admetSAR along with ACD/i-lab software. The docking analysis was performed by using AutoDock 4.2. Concurrently, the NBF-BMFE were experimentally characterized by using liquid chromatography/mass spectrometry (LC/MS) besides their anticancer activity was assessed against HCT-116 human colon cancer cells. Results: The docking studies results showed that the NBF-BMFE phytochemicals showed good hydrogen bond interaction against GSK-3β/Axin (4B7T) and β-catenin/Tcf-4 (1JPW) complex proteins. Moreover, the in silico results of ADMET factors were also satisfying correspondingly. The LC/MS results revealed that the NBF-BMFE contains isocoreopsin, butrin and isobutrin as major compounds, and it has significant anticancer activity (˃100 μM) against HCT-116 human colon cancer cells. Conclusion: Overall our results concluded that all the NBF-BMFE had significant inhibitory effect on HCT-116 cells plus good binding interaction with 4B7T and 1JPW, in specific isocoreopsin, butein and butin showed promising agents to develop as potent drug molecules against colorectal cancer. © 2015, Asian Journal of Pharmaceutical and Clinical Research. All rights reserved.

Huang F.W.D.,Center for Combinatorics | Qin J.,Center for Combinatorics | Reidys C.M.,Center for Combinatorics | Reidys C.M.,Nankai University | And 6 more authors.
Bioinformatics | Year: 2010

Motivation: It has been proven that the accessibility of the target sites has a critical influence on RNA-RNA binding, in general and the specificity and efficiency of miRNAs and siRNAs, in particular. Recently, O(N6) time and O(N4) space dynamic programming (DP) algorithms have become available that compute the partition function of RNA-RNA interaction complexes, thereby providing detailed insights into their thermodynamic properties. Results: Modifications to the grammars underlying earlier approaches enables the calculation of interaction probabilities for any given interval on the target RNA. The computation of the 'hybrid probabilities' is complemented by a stochastic sampling algorithm that produces a Boltzmann weighted ensemble of RNA-RNA interaction structures. The sampling of k structures requires only negligible additional memory resources and runs in O(k·N3). © The Author(s) 2009. Published by Oxford University Press.

Montero J.J.,Telomeres and Telomerase Group | Lopez De Silanes I.,Telomeres and Telomerase Group | Grana O.,Bioinformatics Group | Blasco M.A.,Telomeres and Telomerase Group
Nature Communications | Year: 2016

Telomeres are transcribed generating long non-coding RNAs known as TERRA. Deciphering the role of TERRA has been one of the unsolved issues of telomere biology in the past decade. This has been, in part, due to lack of knowledge on the TERRA loci, thus preventing functional genetic studies. Here, we describe that long non-coding RNAs with TERRA features are transcribed from the human 20q and Xp subtelomeres. Deletion of the 20q locus by using the CRISPR-Cas9 technology causes a dramatic decrease in TERRA levels, while deletion of the Xp locus does not result in decreased TERRA levels. Strikingly, 20q-TERRA ablation leads to dramatic loss of telomere sequences and the induction of a massive DNA damage response. These findings identify chromosome 20q as a main TERRA locus in human cells and represent the first demonstration in any organism of the essential role of TERRA in the maintenance of telomeres.

Kreck B.,University of Kiel | Marnellos G.,CA Technologies | Richter J.,University of Kiel | Krueger F.,Bioinformatics Group | And 2 more authors.
Bioinformatics | Year: 2012

Bisulfite sequencing, a combination of bisulfite treatment and high-throughput sequencing, has proved to be a valuable method for measuring DNA methylation at single base resolution. Here, we present B-SOLANA, an approach for the analysis of two-base encoding (colorspace) bisulfite sequencing data on the SOLiD platform of Life Technologies. It includes the alignment of bisulfite sequences and the determination of methylation levels in CpG as well as non-CpG sequence contexts. B-SOLANA enables a fast and accurate analysis of large raw sequence datasets. © The Author(s) 2011. Published by Oxford University Press. All rights reserved.

Orsini M.,Bioinformatics Group | Carcangiu S.,Bioinformatics Group
Source Code for Biology and Medicine | Year: 2013

Background: Large-scale sequence studies requiring BLAST-based analysis produce huge amounts of data to be parsed. BLAST parsers are available, but they are often missing some important features, such as keeping all information from the raw BLAST output, allowing direct access to single results, and performing logical operations over them.Findings: We implemented BlaSTorage, a Python package that parses multi BLAST results and returns them in a purpose-built object-database format. Unlike other BLAST parsers, BlaSTorage retains and stores all parts of BLAST results, including alignments, without loss of information; a complete API allows access to all the data components.Conclusions: BlaSTorage shows comparable speed of more basic parser written in compiled languages as C++ and can be easily integrated into web applications or software pipelines. © 2013 Orsini and Carcangiu; licensee BioMed Central Ltd.

Goodyer E.,Bioinformatics Group | Gunderson M.,University of Wisconsin - Madison | Dailey S.H.,University of Wisconsin - Madison
Journal of Voice | Year: 2010

During phonation, energy is transferred from the subglottal airflow through the air/mucosa interface that results in the propagation of the mucosal wave in the vocal fold. The vocal fold is soft, and the subglottal mucosa is stiff. We hypothesize that it is highly improbable that there is a rigid boundary between the tissue structures, with a sudden drop in stiffness; and that a gradual change would be more likely to support the efficient transfer of energy from the airflow to the mucosal wave. Our objective was to test this hypothesis by quantifying the change in mucosa stiffness with respect to anatomical position. In this initial study, using five pig larynges, a series of point-specific measurements of mucosa stiffness were taken in a line from the midpoint of the vocal fold toward the trachea. A modified linear skin rheometer adapted for laryngeal elasticity measurement applied shear stress to a series of seven positions at 2-mm intervals starting from the midmembranous vocal fold medial surface. A sinusoidal shear force of 1 g was applied at each point, and resultant displacement curve logged. Using a regression algorithm, the stiffness of the tissue was derived in units of grams force per millimeter displacement. Five readings were taken at each position. The results indicate that there is a linear increase in stiffness with respect to position, increasing as the measurements are taken further from the vocal fold. There is a gradual change in stiffness of the subglottal mucosa of a pig larynx. © 2010 The Voice Foundation.

Schofield P.N.,University of Cambridge | Schofield P.N.,The Jackson Laboratory | Gkoutos G.V.,University of Cambridge | Gruenberger M.,University of Cambridge | And 2 more authors.
DMM Disease Models and Mechanisms | Year: 2010

A major challenge of the post-genomic era is coding phenotype data from humans and model organisms such as the mouse, to permit the meaningful translation of phenotype descriptions between species. This ability is essential if we are to facilitate phenotype-driven gene function discovery and empower comparative pathobiology. Here, we review the current state of the art for phenotype and disease description in mice and humans, and discuss ways in which the semantic gap between coding systems might be bridged to facilitate the discovery and exploitation of new mouse models of human diseases. © 2010. Published by The Company of Biologists Ltd.

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