An environment for knowledge discovery in biology

This paper describes a data mining environment for knowledge discovery in bioinformatics applications. The system has a generic kernel that implements the mining functions to be applied to input primary databases, with a warehouse architecture, of biomedical information. Both supervised and unsupervised classification can be implemented within the kernel and applied to data extracted from the primary database, with the results being suitably stored in a complex object database for knowledge discovery. The kernel also includes a specific high-performance library that allows designing and applying the mining functions in parallel machines. The experimental results obtained by the application of the kernel functions are reported. © 2003 Elsevier Ltd. All rights reserved.

Relationship between global structural parameters and Enzyme Commission hierarchy: Implications for function prediction

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The plant energy-dissipating mitochondrial systems: Depicting the genomic structure and the expression profiles of the gene families of uncoupling protein and alternative oxidase in monocots and dicots

The simultaneous existence of alternative oxidases and uncoupling proteins in plants has raised the question as to why plants need two energy-dissipating systems with apparently similar physiological functions. A probably complete plant uncoupling protein gene family is described and the expression profiles of this family compared with the multigene family of alternative oxidases in Arabidopsis thaliana and sugarcane (Saccharum sp.) employed as dicot and monocot models, respectively. In total, six uncoupling protein genes, AtPUMP1-6, were recognized within the Arabidopsis genome and five (SsPUMP1-5) in a sugarcane EST database. The recombinant AtPUMP5 protein displayed similar biochemical properties as AtPUMP1. Sugarcane possessed four Arabidopsis AOx1-type orthologues (SsAOx1a-1d); no sugarcane orthologue corresponding to Arabidopsis AOx2-type genes was identified. Phylogenetic and expression analyses suggested that AtAOx1d does not belong to the AOx1-type family but forms a new (AOx3-type) family. Tissue-enriched expression profiling revealed that uncoupling protein genes were expressed more ubiquitously than the alternative oxidase genes. Distinct expression patterns among gene family members were observed between monocots and dicots and during chilling stress. These findings suggest that the members of each energy-dissipating system are subject to different cell or tissue/organ transcriptional regulation. As a result, plants may respond more flexibly to adverse biotic and abiotic conditions, in which oxidative stress is involved. © The Author [2006]. Published by Oxford University Press [on behalf of the Society for Experimental Biology]. All rights reserved.

HPLC determination of hemoglobins to establish reference values with the aid of statistics and informatics

The purpose of the present study was to establish reference values for hemoglobins (Hb) using HPLC, in samples containing normal Hb (AA), sickle cell trait without alpha-thalassemia (AS), sickle cell trait with alpha-thalassemia (ASH), sickle cell anemia (SS), and Hb SC disease (SC). The blood samples were analyzed by electrophoresis, HPLC and molecular procedures. The Hb A2 mean was 4.30 ± 0.44% in AS, 4.18 ± 0.42% in ASH, 3.90 ± 1.14% in SS, and 4.39 ± 0.35% in SC. They were similar, but above the normal range. Between the AS and ASH groups, only the amount of Hb S was higher in the AS group. The Hb S mean in the AS group was 38.54 ± 3.01% and in the ASH it was 36.54 ± 3.76%. In the qualitative analysis, using FastMap, distinct groups were seen: AA and SS located at opposite extremes, AS and ASH with overlapping values and intermediate distribution, SC between heterozygotes and the SS group. Hb S was confirmed by allele-specific polymerase chain reaction. The Hb values established will be available for use as a reference for the Brazilian population, drawing attention to the increased levels of Hb A2, which should be considered with caution to prevent incorrect diagnoses. ©FUNPEC-RP.

Optimal clone identifier for genomic shotgun libraries: OC Identifier tool

In DNA microarray experiments, the gene fragments that are spotted on the slides are usually obtained by the synthesis of specific oligonucleotides that are able to amplify genes through PCR. Shotgun library sequences are an alternative to synthesis of primers for the study of each gene in the genome. The possibility of putting thousands of gene sequences into a single slide allows the use of shotgun clones in order to proceed with microarray analysis without a completely sequenced genome. We developed an OC Identifier tool (optimal clone identifier for genomic shotgun libraries) for the identification of unique genes in shotgun libraries based on a partially sequenced genome; this allows simultaneous use of clones in projects such as transcriptome and phylogeny studies, using comparative genomic hybridization and genome assembly. The OC Identifier tool allows comparative genome analysis, biological databases, query language in relational databases, and provides bioinformatics tools to identify clones that contain unique genes as alternatives to primer synthesis. The OC Identifier allows analysis of clones during the sequencing phase, making it possible to select genes of interest for construction of a DNA microarray. ©FUNPEC-RP.

miRNApath: A database of miRNAs, target genes and metabolic pathways

MicroRNAs (miRNAs) are small non-coding RNAs that regulate target gene expression and hence play important roles in metabolic pathways. Recent studies have evidenced the interrelation of miRNAs with cell proliferation, differentiation, development, and diseases. Since they are involved in gene regulation, they are intrinsically related to metabolic pathways. This leads to questions that are particularly interesting for investigating medical and laboratorial applications. We developed an miRNApath online database that uses miRNA target genes to link miRNAs to metabolic pathways. Currently, databases about miRNA target genes (DIANA miRGen), genomic maps (miRNAMap) and sequences (miRBase) do not provide such correlations. Additionally, miRNApath offers five search services and a download area. For each search, there is a specific type of input, which can be a list of target genes, miRNAs, or metabolic pathways, which results in different views, depending upon the input data, concerning relationships between the target genes, miRNAs and metabolic pathways. There are also internal links that lead to a deeper analysis and cross-links to other databases with more detailed information. miRNApath is being continually updated and is available at http://lgmb.fmrp.usp.br/mirnapath. ©FUNPEC-RP.

Routine libraries for pattern recognition in quasispecies.

The results obtained through biological research usually need to be analyzed using computational tools, since manual analysis becomes unfeasible due to the complexity and size of these results. For instance, the study of quasispecies frequently demands the analysis of several, very lengthy sequences of nucleotides and amino acids. Therefore, bioinformatics tools for the study of quasispecies are constantly being developed due to different problems found by biologists. In the present study, we address the development of a software tool for the evaluation of population diversity in quasispecies. Special attention is paid to the localization of genome regions prone to changes, as well as of possible hot spots.

Optimal clone identifier based on dynamic rules and process algebra

The rule creation to clone selection in different projects is a hard task to perform by using traditional implementations to control all the processes of the system. The use of an algebraic language is an alternative approach to manage all of system flow in a flexible way. In order to increase the power of versatility and consistency in defining the rules for optimal clone selection, this paper presents the software OCI 2 in which uses process algebra in the flow behavior of the system. OCI 2, controlled by an algebraic approach was applied in the rules elaboration for clone selection containing unique genes in the partial genome of the bacterium Bradyrhizobium elkanii Semia 587 and in the whole genome of the bacterium Xanthomonas axonopodis pv. citri. Copyright© (2009) by the International Society for Research in Science and Technology.

SKPDB: A structural database of shikimate pathway enzymes

Background: The functional and structural characterisation of enzymes that belong to microbial metabolic pathways is very important for structure-based drug design. The main interest in studying shikimate pathway enzymes involves the fact that they are essential for bacteria but do not occur in humans, making them selective targets for design of drugs that do not directly impact humans.Description: The ShiKimate Pathway DataBase (SKPDB) is a relational database applied to the study of shikimate pathway enzymes in microorganisms and plants. The current database is updated regularly with the addition of new data; there are currently 8902 enzymes of the shikimate pathway from different sources. The database contains extensive information on each enzyme, including detailed descriptions about sequence, references, and structural and functional studies. All files (primary sequence, atomic coordinates and quality scores) are available for downloading. The modeled structures can be viewed using the Jmol program.Conclusions: The SKPDB provides a large number of structural models to be used in docking simulations, virtual screening initiatives and drug design. It is freely accessible at http://lsbzix.rc.unesp.br/skpdb/. © 2010 Arcuri et al; licensee BioMed Central Ltd.

Screening of genomic libraries

Microsatellites, or simple sequence repeats (SSRs), have proven to be an important molecular marker in plant genetics and breeding research. The main strategies to obtain these markers can be through genomic DNA and from expressed sequence tags (ESTs) from mRNA/cDNA libraries. Genetic studies using microsatellite markers have increased rapidly because they can be highly polymorphic, codominant markers and they show heterozygous conserved sequences. Here, we describe a methodology to obtain microsatellite using the enrichment library of DNA genomic sequences. This method is highly efficient to development microsatellite markers especially in plants that do not have available ESTs or genome databases. This methodology has been used to enrich SSR marker libraries in Citrus spp., an important tool to genotype germplasm, to select zygotic hybrids, and to saturate genetic maps in breeding programs. © Springer Science+Business Media, LLC 2013.

Supervised variational relevance learning, an analytic geometric feature selection with applications to omic datasets

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Técnicas de otimização em alinhamentos múltiplos de sequência via Cadeias de Markov

Pós-graduação em Ciência da Computação - IBILCE

Exploring the multifactorial nature of autism through computational systems biology: Calcium and the Rho GTPase RAC1 under the spotlight

Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication accompanied with repetitive behavioral patterns and unusual stereotyped interests. Autism is considered a highly heterogeneous disorder with diverse putative causes and associated factors giving rise to variable ranges of symptomatology. Incidence seems to be increasing with time, while the underlying pathophysiological mechanisms remain virtually uncharacterized (or unknown). By systematic review of the literature and a systems biology approach, our aims were to examine the multifactorial nature of autism with its broad range of severity, to ascertain the predominant biological processes, cellular components, and molecular functions integral to the disorder, and finally, to elucidate the most central contributions (genetic and/or environmental) in silico. With this goal, we developed an integrative network model for gene-environment interactions (GENVI model) where calcium (Ca2+) was shown to be its most relevant node. Moreover, considering the present data from our systems biology approach together with the results from the differential gene expression analysis of cerebellar samples from autistic patients, we believe that RAC1, in particular, and the RHO family of GTPases, in general, could play a critical role in the neuropathological events associated with autism. © 2013 Springer Science+Business Media New York.

Strand Analysis, a free online program for the computational identification of the best RNA interference (RNAi) targets based on Gibbs free energy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

An improved interolog mapping-based computational prediction of protein protein interactions with increased network coverage

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)