RESUMO
The 37th edition of MaxEnt was held in Brazil, hosting several distinguished researchers and students. The workshop offered four tutorials, nine invited talks, twenty four oral presentations and twenty seven poster presentations. All submissions received their first choice between oral and poster presentations. The event held a celebration to Julio Stern's 60th anniversary and awarded two prizes to young researchers. As customary, the workshop had one free afternoon, in which participants visited the city's surroundings and experienced Brazilian food and traditions.
RESUMO
The majority of individuals in the chronic phase of Chagas disease are asymptomatic (indeterminate form). Every year 2-3% of these individuals develop severe clinical manifestations (cardiac and digestive forms). In this study a Trypanosoma cruzi DNA microarray was used to compare the transcript profiles of six human isolates: three from asymptomatic and three from cardiac patients. Seven signals were expressed differentially between the two classes of isolates, including tryparedoxin, surface protease GP63, cyclophilin, some hypothetical proteins and the pre-edited maxicircle gene NADH dehydrogenase subunit 7 (ND7). The approximately 30-fold greater signal in cardiac strains for ND7 was the most pronounced of the group, and differential levels of pre-edited ND7 transcript confirmed the microarray analysis. The ND7 gene from asymptomatic isolates showed a deletion of 455bp from nt 222 to nt 677 relative to ND7 of the CL Brener reference strain. The ND7 gene structure correlated with disease manifestation for 20 isolates from clinically characterised, chronic phase patients. The ND7 lesion produces a truncated product that could impair the function of mitochondrial complex I. Possible links between the integrity of the electron transport chain and symptom presentation are discussed. We propose that ND7 and other genes of the pathway constitute valuable targets for PCR assays in the differential diagnosis of the infective T. cruzi strain. While this hypothesis requires validation by the examination of additional recent parasite isolates from patients with defined pathologies, the identification of specific molecular markers represents a promising advance in the association between parasite genetics and disease pathology.
Assuntos
Cardiomiopatia Chagásica/parasitologia , Doença de Chagas/parasitologia , DNA de Cinetoplasto/genética , Deleção de Genes , Proteínas de Membrana/genética , Proteínas de Protozoários/genética , Trypanosoma cruzi/genética , Adolescente , Adulto , Animais , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , NADH Desidrogenase/genética , Análise de Sequência com Séries de OligonucleotídeosRESUMO
BACKGROUND: The search for enriched (aka over-represented or enhanced) ontology terms in a list of genes obtained from microarray experiments is becoming a standard procedure for a system-level analysis. This procedure tries to summarize the information focussing on classification designs such as Gene Ontology, KEGG pathways, and so on, instead of focussing on individual genes. Although it is well known in statistics that association and significance are distinct concepts, only the former approach has been used to deal with the ontology term enrichment problem. RESULTS: BayGO implements a Bayesian approach to search for enriched terms from microarray data. The R source-code is freely available at http://blasto.iq.usp.br/~tkoide/BayGO in three versions: Linux, which can be easily incorporated into pre-existent pipelines; Windows, to be controlled interactively; and as a web-tool. The software was validated using a bacterial heat shock response dataset, since this stress triggers known system-level responses. CONCLUSION: The Bayesian model accounts for the fact that, eventually, not all the genes from a given category are observable in microarray data due to low intensity signal, quality filters, genes that were not spotted and so on. Moreover, BayGO allows one to measure the statistical association between generic ontology terms and differential expression, instead of working only with the common significance analysis.