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Search Results: 1 - 10 of 462710 matches for " Willy A. Valdivia-Granda "
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Transcriptional Interactions During Smallpox Infection and Identification of Early Infection Biomarkers
Willy A. Valdivia-Granda,Maricel G. Kann,Jose Malaga
Quantitative Biology , 2006,
Abstract: Smallpox is a deadly disease that can be intentionally reintroduced into the human population as a bioweapon. While host gene expression microarray profiling can be used to detect infection, the analysis of this information using unsupervised and supervised classification techniques can produce contradictory results. Here, we present a novel computational approach to incorporate molecular genome annotation features that are key for identifying early infection biomarkers (EIB). Our analysis identified 58 EIBs expressed in peripheral blood mononuclear cells (PBMCs) collected from 21 cynomolgus macaques (Macaca fascicularis) infected with two variola strains via aerosol and intravenous exposure. The level of expression of these EIBs was correlated with disease progression and severity. No overlap between the EIBs co-expression and protein interaction data reported in public databases was found. This suggests that a pathogen-specific re-organization of the gene expression and protein interaction networks occurs during infection. To identify potential genome-wide protein interactions between variola and humans, we performed a protein domain analysis of all smallpox and human proteins. We found that only 55 of the 161 protein domains in smallpox are also present in the human genome. These co-occurring domains are mostly represented in proteins involved in blood coagulation, complement activation, angiogenesis, inflammation, and hormone transport. Several of these proteins are within the EIBs category and suggest potential new targets for the development of therapeutic countermeasures.
Microarray Data Management. An Enterprise Information Approach: Implementations and Challenges
Willy Valdivia-Granda,Christopher Dwan
Quantitative Biology , 2006,
Abstract: The extraction of information form high-throughput experiments is a key aspect of modern biology. Early in the development of microarray technology, researchers recognized that the size of the datasets and the limitations of both computational and visualization techniques restricted their ability to find the biological meaning hidden in the data. In addition, most researchers wanted to make their datasets accessible to others. This resulted in the development of new and advanced data storage, analysis, and visualization tools enabling the cross-platform validation of the experiments and the identification of previously undetected patterns. In order to reap the benefits of this microarray data, researchers have needed to implement database management systems providing integration of different experiments and data types. Moreover, it was necessary to standardize the basic data structure and experimental techniques for the standardization of microarray platforms. In this chapter, we introduce the reader to the major concepts related to the use of controlled vocabularies (ontologies), the definition of Minimum Information About a Microarray Experiment (MIAME) and provide an overview of different microarray data management strategies in use today. We summarize the main characteristics of microarray data storage and sharing strategies including warehouses, datamarts, and federations. The fundamental challenges involved in the distribution, and retrieval of microarray data are presented, along with an overview of some emerging technologies.
Peano Count Trees (P-Trees) and Rule Association Mining for Gene Expression Profiling of Microarray Data
Willy Valdivia-Granda,William Perrizo,Edward Deckard,Francis Larson
Computer Science , 2006,
Abstract: The greatest challenge in maximizing the use of gene expression data is to develop new computational tools capable of interconnecting and interpreting the results from different organisms and experimental settings. We propose an integrative and comprehensive approach including a super-chip containing data from microarray experiments collected on different species subjected to hypoxic and anoxic stress. A data mining technology called Peano count tree (P-trees) is used to represent genomic data in multidimensions. Each microarray spot is presented as a pixel with its corresponding red/green intensity feature bands. Each bad is stored separately in a reorganized 8-separate (bSQ) file format. Each bSQ is converted to a quadrant base tree structure (P-tree) from which a superchip is represented as expression P-trees (EP-trees) and repression P-trees (RP-trees). The use of association rule mining is proposed to derived to meanigingfully organize signal transduction pathways taking in consideration evolutionary considerations. We argue that the genetic constitution of an organism (K) can be represented by the total number of genes belonging to two groups. The group X constitutes genes (X1,Xn) and they can be represented as 1 or 0 depending on whether the gene was expressed or not. The second group of Y genes (Y1,Yn) is expressed at different levels. These genes have a very high repression, high expression, very repressed or highly repressed. However, many genes of the group Y are specie specific and modulated by the products and combinations of genes of the group X. In this paper, we introduce the dSQ and P-tree technology; the biological implications of association rule mining using X and Y gene groups and some advances in the integration of this information using the BRAIN architecture.
The next meta-challenge for Bioinformatics
Willy Valdivia Granda
Bioinformation , 2008,
Abstract: The direct sequencing of uncultivable organisms present in complex biological and environmental samples has opportunities to discover new life forms and metabolic processes. This transformational field, known as metagenomics, is generating massive amounts of molecular information that can overwhelm the performance of conventional analysis and visualization algorithms. Here, I briefly highlight some of the emerging challenges this new discipline presents to the computational biology community and point some of the opportunities to develop applications that can translate metagenomic information into biomedical, agricultural, environmental, and industrial applications.
Transcriptome sequencing and development of an expression microarray platform for the domestic ferret
Carl E Bruder, Suxia Yao, Francis Larson, Jeremy V Camp, Ronald Tapp, Alexis McBrayer, Nicholas Powers, Willy Valdivia Granda, Colleen B Jonsson
BMC Genomics , 2010, DOI: 10.1186/1471-2164-11-251
Abstract: We produced more than 500000 sequence reads that were assembled into 16000 partial ferret genes. These genes were combined with the available ferret sequences in the GenBank to develop a ferret specific microarray platform. Using this array, we detected tissue specific expression patterns which were confirmed by quantitative real time PCR assays. We also present a set of 41 ferret genes with even transcription profiles across the tested tissues, indicating their usefulness as housekeeping genes.The tools developed in this study allow for functional genomic analysis and make further development of reagents for the ferret model possible.The ferret is an important model for pulmonary research studies because of the long trachea, large lung capacity and bronchiolar branching. It is commonly used for studies of infectious diseases and is susceptible to infection with a large number of pathogens, such as influenza virus, severe acute respiratory syndrome (SARS) corona virus, and canine distemper virus [1-8]. The ferret is an essential model for influenza research as it develops a number of the clinical symptoms of influenza that are also seen in humans and, in contrast to mice, can be infected by human isolates of influenza virus [9]. With the recent two-animal ruling by the US Food and Drug Administration (FDA) for the licensing of drugs or vaccines directed against diseases of low or no incidence, the ferret represents an inexpensive small, non-rodent animal model. Despite the fact that ferrets have been used in biomedical research for decades, little is known about the genome of M. p. furo. Currently, there are only a limited number of partial or full length cDNAs present in the GenBank. This not only impacts the number of molecular genetic assays available for analysis, but also hinders the development of antibody-based assays, such as flow cytometry. The lack of reagents for molecular analysis of the mechanisms involved in infection and immunogenic protection is rest
New infrared cut-off for the holographic scalar fields models of dark energy
L. N. Granda,A. Oliveros
Physics , 2008, DOI: 10.1016/j.physletb.2008.12.025
Abstract: Introducing a new infrared cut-off for the holographic dark-energy, we study the correspondence between the quintessence, tachyon, K-essence and dilaton energy density with this holographic dark energy density in the flat FRW universe. This correspondence allows to reconstruct the potentials and the dynamics for the scalar fields models, which describe accelerated expansion.
Infrared cut-off proposal for the Holographic density
L. N. Granda,A. Oliveros
Physics , 2008, DOI: 10.1016/j.physletb.2008.10.017
Abstract: We propose an infrared cut-off for the holographic the dark-energy, which besides the square of the Hubble scale also contains the time derivative of the Hubble scale. This avoids the problem of causality which appears using the event horizon area as the cut-off, and solves the coincidence problem.
El uso de la máscara laríngea en un ni o con síndrome de Goldenhar
Willy Orcada García
Revista Colombiana de Anestesiología , 2006,
Evaluation of a Modified Scleral Contact Lens as a Riboflavin Delivery Device for Corneal Collagen Crosslinking  [PDF]
Ricardo Torres Soares, Neil F. Novo, Willy Marcus Fran?a
Open Journal of Ophthalmology (OJOph) , 2017, DOI: 10.4236/ojoph.2017.74036
Introduction: Keratoconus is a complex corneal disease that reduces visual acuity by progressively modifying the corneal shape and thickness, usually producing myopia and irregular astigmatism. Corneal collagen crosslinking with riboflavin + ultraviolet-A radiation (CXL) has become a widely accepted treatment for progressive keratoconus. During CXL, riboflavin administration is performed by repeated manual instillation of solution drops on the cornea for 30 minutes, a procedure that is often uncomfortable for many patients and that consumes surgical facilities and staff resources. In this study, especially modified scleral contact lenses (MSCL) were employed for delivering riboflavin to the cornea during CXL. Objective: The study aimed at evaluating the safety and efficacy of MSCL as a drug delivery system, verifying if anterior chamber flare confirms riboflavin penetration and describes the impact on patient comfort and optimization of surgical staff and facility resources. Material and Method: This study included 8 eyes of 6 patients aged 16 - 25 years old with history of progressive keratoconus. After mechanical removal of corneal epithelium, the concave surface of the modified scleral contact lens was filled with riboflavin solution and the lens was placed on the patient’s eye during 30 minutes. The lens design allows the formation of a riboflavin layer between the lens and the exposed corneal stroma to facilitate riboflavin penetration. Patients with lens were allowed to stand up and wait for the second UVA phase outside the surgical room. Riboflavin diffusion was confirmed by biomicroscopic examination of the corneal stroma and anterior chamber with the lens in place. Patients returned and the lens was removed before UV-A irradiation at 3 mW/cm2 for 30 minutes. Statistical analysis was performed by comparing the following parameters of each patient pre- and post-CXL: Spherical equivalent (Sph.Eq.), Mean simulated keratometry (SimK-m) and corrected distance visual acuity (CDVA) using the Wilcoxon method for non-parametric data (p < 0. 05). Results: The MSCL allowed patients to be transferred from the surgical room to wait for corneal impregnation with riboflavin. The MSCL was effective in delivering riboflavin to the cornea as confirmed by biomicroscopic examination of the cornea and anterior chamber. No intraoperative or postoperative complications were observed. MSCL use improved the patient comfort and reduced the burden
Codon usage in vertebrates is associated with a low risk of acquiring nonsense mutations
Pirmin Schmid, Willy A Flegel
Journal of Translational Medicine , 2011, DOI: 10.1186/1479-5876-9-87
Abstract: We developed an event based model to calculate the risk of acquiring nonsense mutations in coding sequences. Complete coding sequences and genomes of 40 eukaryotes were analyzed for GC and CpG content, codon usage, and the associated risk of acquiring nonsense mutations. We included one species per genus for all eukaryotes with available reference sequence.We discovered that the codon usage bias detected in genomes of high GC content decreases the risk of acquiring nonsense mutations (Pearson's r = -0.95; P < 0.0001). In the genomes of all examined vertebrates, including humans, this risk was lower than expected (0.93 ± 0.02; mean ± SD) and lower than the risk in genomes of non-vertebrates (1.02 ± 0.13; P = 0.019).While the maintenance of a high GC content is energetically costly, it is associated with a codon usage bias harboring a low risk of acquiring nonsense mutations. The reduced exposure to this risk may contribute to the fitness of vertebrates.Codon usage bias in genomes is relevant for organisms. It influences the translation speed and thus gene expression [1]. Artificially deoptimized codon usage can decrease gene expression and create an attenuated viral virulence that may be used for vaccine production [2]. HIV-1 modifies the tRNA pool of the infected cells to increase translation efficiency of its own genes [3]. Initial studies on codon usage bias were based on few genes in single species: lists of the codon usage [4], determination of the number of codons used in genes [5], and models, such as the codon adaptation index (CAI). The CAI compared the codon usage of each gene with an "optimal" codon usage, which is inferred from high-expression gene sets [6]. Whole genome sequencing data and newer algorithms have allowed researchers to overcome previous limitations, study more genes, and classify genes in more detailed categories [7]. Codon usage bias is associated with tRNA concentration [8] and also the GC content of genomes [9-12].Loss-of-function mutat
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