RESUMO
BACKGROUND: Human protein-protein interaction (PPI) data is essential to network and systems biology studies. PPI data can help biochemists hypothesize how proteins form complexes by binding to each other, how extracellular signals propagate through post-translational modification of de-activated signaling molecules, and how chemical reactions are coupled by enzymes involved in a complex biological process. Our capability to develop good public database resources for human PPI data has a direct impact on the quality of future research on genome biology and medicine. RESULTS: The database of Human Annotated and Predicted Protein Interactions (HAPPI) version 2.0 is a major update to the original HAPPI 1.0 database. It contains 2,922,202 unique protein-protein interactions (PPI) linked by 23,060 human proteins, making it the most comprehensive database covering human PPI data today. These PPIs contain both physical/direct interactions and high-quality functional/indirect interactions. Compared with the HAPPI 1.0 database release, HAPPI database version 2.0 (HAPPI-2) represents a 485% of human PPI data coverage increase and a 73% protein coverage increase. The revamped HAPPI web portal provides users with a friendly search, curation, and data retrieval interface, allowing them to retrieve human PPIs and available annotation information on the interaction type, interaction quality, interacting partner drug targeting data, and disease information. The updated HAPPI-2 can be freely accessed by Academic users at http://discovery.informatics.uab.edu/HAPPI . CONCLUSIONS: While the underlying data for HAPPI-2 are integrated from a diverse data sources, the new HAPPI-2 release represents a good balance between data coverage and data quality of human PPIs, making it ideally suited for network biology.
Assuntos
Anotação de Sequência Molecular , Mapeamento de Interação de Proteínas/métodos , Bases de Dados de Proteínas , Humanos , InternetRESUMO
BACKGROUND: Current network-based microarray analysis uses the information of interactions among concerned genes/gene products, but still considers each gene expression individually. We propose an organized knowledge-supervised approach - Integrative eXpression Profiling (IXP), to improve microarray classification accuracy, and help discover groups of genes that have been too weak to detect individually by traditional ways. To implement IXP, ant colony optimization reordering (ACOR) algorithm is used to group functionally related genes in an ordered way. RESULTS: Using Alzheimer's disease (AD) as an example, we demonstrate how to apply ACOR-based IXP approach into microarray classifications. Using a microarray dataset - GSE1297 with 31 samples as training set, the result for the blinded classification on another microarray dataset - GSE5281 with 151 samples, shows that our approach can improve accuracy from 74.83% to 82.78%. A recently-published 1372-probe signature for AD can only achieve 61.59% accuracy in the same condition. The ACOR-based IXP approach also has better performance than the IXP approach based on classic network ranking, graph clustering, and random-ordering methods in an overall classification performance comparison. CONCLUSIONS: The ACOR-based IXP approach can serve as a knowledge-supervised feature transformation approach to increase classification accuracy dramatically, by transforming each gene expression profile to an integrated expression files as features inputting into standard classifiers. The IXP approach integrates both gene expression information and organized knowledge - disease gene/protein network topology information, which is represented as both network node weights (local topological properties) and network node orders (global topological characteristics).
Assuntos
Perfilação da Expressão Gênica/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Algoritmos , Doença de Alzheimer/metabolismo , Análise por Conglomerados , Humanos , Análise de Sequência com Séries de Oligonucleotídeos/classificação , Mapeamento de Interação de ProteínasRESUMO
BACKGROUND: Over the past decade, pathway and gene-set enrichment analysis has evolved into the study of high-throughput functional genomics. Owing to poorly annotated and incomplete pathway data, researchers have begun to combine pathway and gene-set enrichment analysis as well as network module-based approaches to identify crucial relationships between different molecular mechanisms. METHODS: To meet the new challenge of molecular phenotype discovery, in this work, we have developed an integrated online database, the Pathway And Gene Enrichment Database (PAGED), to enable comprehensive searches for disease-specific pathways, gene signatures, microRNA targets, and network modules by integrating gene-set-based prior knowledge as molecular patterns from multiple levels: the genome, transcriptome, post-transcriptome, and proteome. RESULTS: The online database we developed, PAGED http://bio.informatics.iupui.edu/PAGED is by far the most comprehensive public compilation of gene sets. In its current release, PAGED contains a total of 25,242 gene sets, 61,413 genes, 20 organisms, and 1,275,560 records from five major categories. Beyond its size, the advantage of PAGED lies in the explorations of relationships between gene sets as gene-set association networks (GSANs). Using colorectal cancer expression data analysis as a case study, we demonstrate how to query this database resource to discover crucial pathways, gene signatures, and gene network modules specific to colorectal cancer functional genomics. CONCLUSIONS: This integrated online database lays a foundation for developing tools beyond third-generation pathway analysis approaches on for discovering molecular phenotypes, especially for disease-associated pathway/gene-set enrichment analysis.
Assuntos
Biologia Computacional/métodos , Bases de Dados Genéticas , Redes Reguladoras de Genes , Genômica/métodos , Algoritmos , Neoplasias Colorretais/genética , Genoma Humano , Humanos , Proteoma , Software , TranscriptomaRESUMO
BACKGROUND: Network pharmacology has emerged as a new topic of study in recent years. It aims to study the myriad relationships among proteins, drugs, and disease phenotypes. The concept of molecular connectivity maps has been proposed to establish comprehensive knowledge links between molecules of interest in a given biological context. Molecular connectivity maps between drugs and genes/proteins in specific disease contexts can be particularly valuable, since the functional approach with these maps helps researchers gain global perspectives on both the therapeutic profiles and toxicological profiles of candidate drugs. METHODS: To assess drug pharmacological effect, we assume that "ideal" drugs for a patient can treat or prevent the disease by modulating gene expression profiles of this patient to the similar level with those in healthy people. Starting from this hypothesis, we build comprehensive disease-gene-drug connectivity relationships with drug-protein directionality (inhibit/activate) information based on a computational connectivity maps (C²Maps) platform. An interactive interface for directionality annotation of drug-protein pairs with literature evidences from PubMed has been added to the new version of C²Maps. We also upload the curated directionality information of drug-protein pairs specific for three complex diseases - breast cancer, colorectal cancer and Alzheimer disease. RESULTS: For relevant drug-protein pairs with directionality information, we use breast cancer as a case study to demonstrate the functionality of disease-specific searching. Based on the results obtained from searching, we perform pharmacological effect evaluation for two important breast cancer drugs on treating patients diagnosed with different breast cancer subtypes. The evaluation is performed on a well-studied breast cancer gene expression microarray dataset to portray how useful the updated C²Maps is in assessing drug efficacy and toxicity information. CONCLUSIONS: The C²Maps platform is an online bioinformatics resource that provides biologists with directional relationships between drugs and genes/proteins in specific disease contexts based on network mining, literature mining, and drug effect annotating. A new insight to assess overall drug efficacy and toxicity can be provided by using the C²Maps platform to identify disease relevant proteins and drugs. The case study on breast cancer correlates very well with the existing pharmacology of the two breast cancer drugs and highlights the significance of C²Maps database.
Assuntos
Biologia Computacional , Bases de Dados Factuais , Antineoplásicos/metabolismo , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Internet , Proteínas/metabolismoRESUMO
BACKGROUND: Pathway-oriented experimental and computational studies have led to a significant accumulation of biological knowledge concerning three major types of biological pathway events: molecular signaling events, gene regulation events, and metabolic reaction events. A pathway consists of a series of molecular pathway events that link molecular entities such as proteins, genes, and metabolites. There are approximately 300 biological pathway resources as of April 2009 according to the Pathguide database; however, these pathway databases generally have poor coverage or poor quality, and are difficult to integrate, due to syntactic-level and semantic-level data incompatibilities. RESULTS: We developed the Human Pathway Database (HPD) by integrating heterogeneous human pathway data that are either curated at the NCI Pathway Interaction Database (PID), Reactome, BioCarta, KEGG or indexed from the Protein Lounge Web sites. Integration of pathway data at syntactic, semantic, and schematic levels was based on a unified pathway data model and data warehousing-based integration techniques. HPD provides a comprehensive online view that connects human proteins, genes, RNA transcripts, enzymes, signaling events, metabolic reaction events, and gene regulatory events. At the time of this writing HPD includes 999 human pathways and more than 59,341 human molecular entities. The HPD software provides both a user-friendly Web interface for online use and a robust relational database backend for advanced pathway querying. This pathway tool enables users to 1) search for human pathways from different resources by simply entering genes/proteins involved in pathways or words appearing in pathway names, 2) analyze pathway-protein association, 3) study pathway-pathway similarity, and 4) build integrated pathway networks. We demonstrated the usage and characteristics of the new HPD through three breast cancer case studies. CONCLUSION: HPD http://bio.informatics.iupui.edu/HPD is a new resource for searching, managing, and studying human biological pathways. Users of HPD can search against large collections of human biological pathways, compare related pathways and their molecular entity compositions, and build high-quality, expanded-scope disease pathway models. The current HPD software can help users address a wide range of pathway-related questions in human disease biology studies.
Assuntos
Bases de Dados Factuais , Software , Biologia de Sistemas/métodos , Biologia Computacional/métodos , Bases de Dados de Proteínas , Humanos , Internet , Proteínas/químicaRESUMO
OBJECTIVE: To compare normothermic (35°C-36°C) versus hypothermic (28°C) cardiopulmonary bypass (CPB) in paediatric patients undergoing open heart surgery to test the hypothesis that normothermic CPB perfusion maintains the functional integrity of major organ systems leading to faster recovery. METHODS: Two single-centre, randomised controlled trials (known as Thermic-1 and Thermic-2, respectively) were carried out to compare the effectiveness and acceptability of normothermic versus hypothermic CPB in children with congenital heart disease undergoing open heart surgery. In both studies, the co-primary clinical outcomes were duration of inotropic support, intubation time and postoperative hospital stay. RESULTS: In total, 200 participants were recruited; 59 to the Thermic-1 study and 141 to the Thermic-2 study. 98 patients received normothermic CPB and 102 patients received hypothermic CPB. There were no significant differences between the treatment groups for any of the co-primary outcomes: inotrope duration HR=1.01, 95% CI (0.72 to 1.41); intubation time HR=1.14, 95% CI (0.86 to 1.51); postoperative hospital stay HR=1.06, 95% CI (0.80 to 1.40). Differences favouring normothermia were found in urea nitrogen at 2 days geometric mean ratio (GMR)=0.86 95% CI (0.77 to 0.97); serum creatinine at 3 days GMR=0.89, 95% CI (0.81 to 0.98); urinary albumin at 48 hours GMR=0.32, 95% CI (0.14 to 0.74) and neutrophil gelatinase-associated lipocalin at 4 hours GMR=0.47, 95% CI (0.22 to 1.02), but not at other postoperative time points. CONCLUSIONS: Normothermic CPB is as safe and effective as hypothermic CPB and can be routinely adopted as a perfusion strategy in low-risk infants and children undergoing open heart surgery. TRIAL REGISTRATION NUMBER: ISRCTN93129502.
Assuntos
Temperatura Corporal/fisiologia , Ponte Cardiopulmonar/métodos , Cardiopatias Congênitas/cirurgia , Hipotermia Induzida , Complicações Pós-Operatórias , Nitrogênio da Ureia Sanguínea , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Criança , Creatinina/análise , Feminino , Humanos , Hipotermia Induzida/efeitos adversos , Hipotermia Induzida/métodos , Lactente , Lipocalina-2/análise , Masculino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/metabolismo , Complicações Pós-Operatórias/prevenção & controle , Albumina Sérica Humana/urina , Resultado do TratamentoRESUMO
OBJECTIVES: Treatment of infants with tetralogy of Fallot (ToF) has evolved in the last two decades with increasing use of primary surgical repair (PrR) and transcatheter right ventricular outflow tract palliation (RVOTd), and fewer systemic-to-pulmonary shunts (SPS). We aim to report contemporary results using these treatment options in a comparative study. METHODS: This a retrospective study using data from the UK National Congenital Heart Disease Audit. All infants (n=1662, median age 181 days) with ToF and no other complex defects undergoing repair or palliation between 2000 and 2013 were considered. Matching algorithms were used to minimise confounding due to lower age and weight in those palliated. RESULTS: Patients underwent PrR (n=1244), SPS (n=311) or RVOTd (n=107). Mortality at 12 years was higher when repair or palliation was performed before the age of 60 days rather than after, most significantly for primary repair (18.7% vs 2.2%, P<0.001), less so for RVOTd (10.8% vs 0%, P=0.06) or SPS (12.4% vs 8.3%, P=0.2). In the matched groups of patients, RVOTd was associated with more right ventricular outflow tract (RVOT) reinterventions (HR=2.3, P=0.05 vs PrR, HR=7.2, P=0.001 vs SPS) and fewer pulmonary valve replacements (PVR) (HR=0.3 vs PrR, P=0.05) at 12 years, with lower mortality after complete repair (HR=0.2 versus PrR, P=0.09). CONCLUSIONS: We found that RVOTd was associated with more RVOT reinterventions, fewer PVR and fewer deaths when compared with PrR in comparable, young infants, especially so in those under 60 days at the time of the first procedure.
Assuntos
Cateterismo Cardíaco , Procedimentos Cirúrgicos Cardíacos , Cuidados Paliativos/métodos , Tetralogia de Fallot/terapia , Fatores Etários , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/mortalidade , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Auditoria Médica , Estudos Retrospectivos , Fatores de Risco , Tetralogia de Fallot/diagnóstico , Tetralogia de Fallot/mortalidade , Tetralogia de Fallot/cirurgia , Fatores de Tempo , Resultado do Tratamento , Reino UnidoRESUMO
BACKGROUND: The exact types, frequency, and consequences of early congenital cardiac reoperations are not well known. We aim to describe them and evaluate the potential of early reoperations as a metric for quality of care. METHODS: A retrospective analysis of the 2005 through 2010 National Congenital Heart Disease Audit database was performed. An early cardiac reoperation sequence was defined as one taking place within a 30-day episode. RESULTS: A total of 18,489 cardiac surgical procedures were analyzed, 652 (3.5%) being early cardiac reoperations, part of 588 sequences. The most common index procedures were arterial shunt, coarctation or hypoplasia of the aorta repair, and pulmonary artery banding. The most common reoperations were arterial shunt, pulmonary artery band, and ventricular septal defect procedures. The 60-day mortality was significantly higher in patients having an early reoperation, with 93 early deaths, compared with those who did not (15.8% versus 3%; p < 0.001). From these 93 early deaths, 42 (45%) followed a Norwood, arterial shunt, or pulmonary artery band performed as an index or reoperation. Reoperations were classified as related and unrelated to the index procedure. A related-to-unrelated reoperation ratio was calculated, ranging from 0.2 for coarctation or hypoplasia to 9.0 for atrioventricular septal defect repair. CONCLUSIONS: Early reoperations can be variably related to the index procedure, ranging from repeat of index to repair of associated defects and staged procedures, resulting in different patterns of reoperation types by relationship to the index. Cardiac reoperations within 30 days are associated with increased mortality, which is clustered around a small number of procedures.
Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Cardiopatias Congênitas/mortalidade , Cardiopatias Congênitas/cirurgia , Qualidade da Assistência à Saúde , Reoperação/métodos , Adolescente , Fatores Etários , Procedimentos Cirúrgicos Cardíacos/métodos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Criança , Pré-Escolar , Estudos de Coortes , Bases de Dados Factuais , Educação Médica Continuada , Feminino , Cardiopatias Congênitas/diagnóstico , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Medição de Risco , Romênia , Fatores Sexuais , Estatísticas não Paramétricas , Taxa de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: The systemic-to-pulmonary shunt (SPS) remains an important palliative therapy in many congenital heart defects. Unlike other surgical treatments, the mortality after shunt operations has risen. We used an audit dataset to investigate potential reasons for this change and to report national results. METHODS: A total of 1993 patients classified in 13 diagnoses underwent an SPS procedure between 2000 and 2013. Indication trends by era and also results before repair or next stage are reported. A dynamic hazard model with competing risks and modulated renewal was used to determine predictors of outcomes. RESULTS: The usage of SPS in Tetralogy of Fallot (ToF) has significantly decreased in the last decade, with cases of single ventricle (SV) and pulmonary atresia (PA) with septal communication increasing (P < 0.001 for trends). This is correlated with an increase of early mortality from 5.1% in the first half of the decade to 9.8% in the latter (P = 0.007 for trend). At 1.5 years, 13.9% of patients have died, 17.8% had a shunt reintervention and 68.3% of patients are alive and reintervention-free. Low weight, PA-intact septum, SV and central shunt type are among the factors associated with increased mortality, whereas PA-ventricular septal defect, corrected transposition, isomerism, central shunt and low weight are among those associated with increased reintervention, also having a dynamic effect on the relative risk when compared with ToF patients. Shunt reinterventions are not associated with worse outcomes when adjusted by other covariates, but they do have higher 30-day mortality if occurring earlier than 30 days from the index (P < 0.001). Patients operated in later years were found to have significantly lower survival at a distance from index. CONCLUSIONS: The observed historical rise in mortality for shunt operations relates to complex factors including changing practice for repair of ToF and for univentricular palliation. PA and SV patients are the groups of patients at the highest risk of death. Small size, shunt type and underlying anatomical defect are the main determinants of outcomes. Trends in indication and mortality seem to indicate that more severely ill patients benefit from shunting, but with an increase in mortality.
Assuntos
Procedimento de Blalock-Taussig/métodos , Cardiopatias Congênitas/cirurgia , Procedimento de Blalock-Taussig/mortalidade , Bases de Dados Factuais , Feminino , Cardiopatias Congênitas/mortalidade , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Auditoria Médica , Seleção de Pacientes , Prognóstico , Atresia Pulmonar/mortalidade , Atresia Pulmonar/cirurgia , Reoperação/métodos , Reoperação/estatística & dados numéricos , Fatores de Risco , Tetralogia de Fallot/mortalidade , Tetralogia de Fallot/cirurgia , Resultado do Tratamento , Reino Unido/epidemiologiaRESUMO
OBJECTIVE: The combination of total arterial revascularisation and avoidance of cardiopulmonary bypass may provide additional benefits to patients receiving complete arterial grafting with cardiopulmonary bypass. We performed a propensity-matched cohort study of complete arterial off-pump and on-pump coronary surgery and examined differences in in-hospital mortality and morbidity. METHODS: Three hundred and sixty patients who underwent off-pump coronary surgery with complete arterial grafting between April 1997 and September 2002 were matched to 360 patients who received coronary surgery with cardiopulmonary bypass and complete arterial grafting. To match off-pump with unique on-pump patients, logistic regression was used to develop a propensity score for off-pump surgery. The C statistic for this model was 0.79. Off-pump patients were matched to unique on-pump patients with an identical 5-digit propensity score. If this could not be done, we then proceeded to a 4-, 3-, 2-, or 1-digit match. RESULTS: Patient characteristics were well matched. There was no difference in in-hospital mortality between the groups. Off-pump patients were less likely to develop sternal wound infections compared to the on-pump group (2.5 versus 5.8%; P=0.03), and had significantly lower blood loss (675 versus 780 ml; P<0.001), red blood cell unit transfusion (8.6 versus 38.9%; P<0.001), enzyme rises (13 versus 23 U/l; P<0.001), inotrope support (11.9 versus 28.9%; P<0.001), and ventilation times (5 versus 8 h; P<0.001). Intensive care unit and hospital stay were also significantly lower in the off-pump patients. CONCLUSIONS: Off-pump coronary surgery with complete arterial revascularisation can significantly reduce in-hospital morbidity and lengths of stay compared to conventional on-pump coronary surgery.
Assuntos
Ponte de Artéria Coronária/mortalidade , Mortalidade Hospitalar , Revascularização Miocárdica/métodos , Idoso , Prótese Vascular , Estudos de Coortes , Ponte de Artéria Coronária/métodos , Ponte de Artéria Coronária sem Circulação Extracorpórea/métodos , Ponte de Artéria Coronária sem Circulação Extracorpórea/mortalidade , Vasos Coronários/cirurgia , Feminino , Humanos , Tempo de Internação , Masculino , Artéria Torácica Interna/transplante , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Reoperação , Fatores de Risco , Infecção da Ferida Cirúrgica/etiologia , Resultado do TratamentoRESUMO
BACKGROUND: Five infants operated on for anomalous origin of the left coronary artery from the pulmonary artery were retrospectively analyzed. The mean age at operation was 12 +/- 6.7 weeks (95% confidence interval, 3.5 to 20 weeks), and mean weight at operation was 4.43 +/- 0.68 kg (95% confidence interval, 3.7 to 5.27 kg). All babies presented in infancy with left ventricular failure. Three had evidence of ischemia with left ventricular strain, and two had Q waves in anterolateral leads on electrocardiograph. Cross-sectional echocardiography showed dilated left ventricles with poor contractility in all babies with fractional shortening of 15.8% +/- 4.02% (95% confidence interval, 12% to 20%); moderate mitral regurgitation was seen in all babies. METHODS: All babies underwent operation as soon as the diagnosis was made. Four babies had direct reimplantation of left coronary artery into the aorta, and 1 had tunnel repair. Intraaortic balloon counterpulsation was used in 1 baby for hemodynamic instability and as prophylaxis in the remaining 4 babies postoperatively for 115 +/- 26.2 hours (95% confidence interval, 72 to 144 hours). RESULTS: All babies had delayed closure of the chest. There was no operative mortality. One baby was reoperated on for tunnel stenosis as well as pulmonary stenosis 4 months after primary repair. All babies were followed for 192 patient-months and show an improved fractional shortening. CONCLUSIONS: Early operation, early institution of intraaortic balloon counter pulsation for left ventricular support, and delayed sternal closure are the key to good results.
Assuntos
Anomalias dos Vasos Coronários/cirurgia , Artéria Pulmonar/anormalidades , Anomalias dos Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Ecocardiografia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Contração Miocárdica/fisiologia , Complicações Pós-Operatórias/diagnóstico por imagem , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/cirurgia , Reoperação , Estudos Retrospectivos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/cirurgiaRESUMO
Diastolic dysfunction is common in infants and neonates with left ventricular (LV) outflow tract obstruction and may lead to low-cardiac output in the postoperative period. We present a management strategy for severe postrepair diastolic dysfunction in an infant with critical congenital aortic stenosis and LV hypertrophy, employing ß-blockade and levosimendan.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Estenose da Valva Aórtica/cirurgia , Circulação Extracorpórea/métodos , Implante de Prótese de Valva Cardíaca/efeitos adversos , Hidrazonas/uso terapêutico , Piridazinas/uso terapêutico , Disfunção Ventricular/terapia , Estenose da Valva Aórtica/congênito , Cardiotônicos/uso terapêutico , Diástole , Quimioterapia Combinada , Seguimentos , Humanos , Recém-Nascido , Masculino , Complicações Pós-Operatórias , Simendana , Disfunção Ventricular/etiologia , Disfunção Ventricular/fisiopatologia , Obstrução do Fluxo Ventricular Externo/cirurgiaRESUMO
Cardiac surgery in patients with osteogenesis imperfecta is challenging as the friability of the tissues can be hazardous before, during, and after the operation. A multidisciplinary approach with a planned strategy is essential for the successful management of these patients. We present a 6-year old child with osteogenesis imperfecta, who underwent ventricular septal defect closure without any complication.
Assuntos
Comunicação Interventricular/complicações , Comunicação Interventricular/cirurgia , Osteogênese Imperfeita/complicações , Criança , Humanos , Masculino , Fatores de RiscoRESUMO
In many cases, crucial genes show relatively slight changes between groups of samples (e.g. normal vs. disease), and many genes selected from microarray differential analysis by measuring the expression level statistically are also poorly annotated and lack of biological significance. In this paper, we present an innovative approach - network expansion and pathway enrichment analysis (NEPEA) for integrative microarray analysis. We assume that organized knowledge will help microarray data analysis in significant ways, and the organized knowledge could be represented as molecular interaction networks or biological pathways. Based on this hypothesis, we develop the NEPEA framework based on network expansion from the human annotated and predicted protein interaction (HAPPI) database, and pathway enrichment from the human pathway database (HPD). We use a recently-published microarray dataset (GSE24215) related to insulin resistance and type 2 diabetes (T2D) as case study, since this study provided a thorough experimental validation for both genes and pathways identified computationally from classical microarray analysis and pathway analysis. We perform our NEPEA analysis for this dataset based on the results from the classical microarray analysis to identify biologically significant genes and pathways. Our findings are not only consistent with the original findings mostly, but also obtained more supports from other literatures.
Assuntos
Biologia Computacional/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Algoritmos , Bases de Dados Factuais , Perfilação da Expressão Gênica , HumanosRESUMO
Ventricular septal defect closure with a fenestrated patch is a recognized rescue maneuver to decrease the risk of right ventricular failure after complete repair in patients with pulmonary atresia. If the fenestration needs surgical closure, severe calcification of the patch may make it extremely difficult. We describe the closure of such a defect in a 6-year-old boy, using a double Dacron patch sandwich.
Assuntos
Calcinose/cirurgia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Comunicação Interventricular/cirurgia , Pericárdio/transplante , Implantação de Prótese , Calcinose/etiologia , Criança , Comunicação Interventricular/fisiopatologia , Humanos , Masculino , Polietilenotereftalatos , Desenho de Prótese , Reoperação , Técnicas de Sutura , Resultado do TratamentoRESUMO
Identifying candidate genes/proteins involved in human disease specific molecular pathways or networks has been a primary focus of biomedical research. Although node ranking and graph clustering methods can help identify localized topological properties in a network, it remains unclear how the results should be interpreted in biological functional context in systems-level. In complex biomolecular interaction networks, biomolecular entities may not have absolute ranks or clear cluster boundary among them. We presented Ant Colony Optimization Reordering (ACOR) method to examine emerging network properties. The task of reordering nodes is represented as the problem of finding optimal density distribution of "ant colony" on all nodes of the network. We applied ACOR method to re-analyze a yeast protein-protein interaction (PPI) network annotated with functional information (i.e., lethality), which revealed intriguing systems-level functional features.
Assuntos
Redes e Vias Metabólicas , Mapeamento de Interação de Proteínas/estatística & dados numéricos , Proteínas de Saccharomyces cerevisiae/metabolismo , Engenharia Biomédica , Modelos Biológicos , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Biologia de SistemasRESUMO
The identification of molecular entities involved in human diseases has been a primary focus of post-genomic biomedicine for pursuing the clinical goals of diagnosis and therapeutic treatment. An emerging perspective in systems biology is that the essential biological roles of molecular entities seem to be well correlated with general molecular network properties. Several types of biological complex networks, including protein interaction networks, have a feature of scale-free networks that relates to fractals (multi-scale self-similarity). Using Alzheimer's Disease (AD) as a case study, we constructed an AD-relevant protein interaction subnetwork. We further developed a computational framework based on Ant Colony Optimisation (ACO) to rank disease network relevant nodes. In this framework, the task of ranking nodes is represented as the problem of finding optimal density distributions of 'ant colonies' on all nodes of the network. Our results also revealed fractal-like properties of the network.
Assuntos
Doença de Alzheimer/metabolismo , Proteínas/química , Biologia de Sistemas/métodos , HumanosRESUMO
OBJECTIVE: We examined the effect of cardiac comorbidity on mortality and postoperative complications following surgery for primary non-small cell lung cancer. METHODS: Between October 2001 to December 2005, 1067 consecutive patients underwent lung resection for primary cancer within a single centre; patient data was collected prospectively. Two hundred and seventy-one patients had a history of cardiac comorbidity, which included 196 angina, 118 myocardial infarction, 36 revascularisation, 10 congestive cardiac failure and 19 rhythm disorders (numbers not mutually exclusive). To account for differences in case-mix we used logistic regression to develop a propensity score for cardiac comorbidity group membership and then performed a propensity-matched analysis. Kaplan-Meier curves were used to assess follow-up mortality. RESULTS: Patients with cardiac comorbidity were more likely to be hypertensive, have severe dyspnoea, diabetes, current or ex-smokers and were older. After performing propensity matching to account for these differences we successfully matched 199 patients with cardiac comorbidity to 398 patients with no cardiac history. There was no difference in in-hospital mortality (2.5% vs 3%, p=0.73), myocardial infarction (0.5% vs 0.3%, p>0.99), arrhythmia (15.6% vs 14.1%, p=0.62), renal failure (2% vs 1.5%, p=0.65), stroke (0.5% vs 0.3%, p>0.99), respiratory insufficiency (4% vs 3.3%, p=0.64), reintubation (1% vs 2.5%, p=0.35), tracheostomy (4% vs 7.8%, p=0.08), intensive care readmission (8.5% vs 6.5%, p=0.37) and length of stay (8 days vs 8 days, p=0.98). Three-year survival was similar (61.4% vs 56.2%, p=0.39). No differences in outcomes existed with different cardiac conditions. CONCLUSION: With careful assessment and patient selection, patients with cardiac comorbidity were not found to be at increased risk of mortality and morbidity following lung resection for primary non-small cell lung cancer in a propensity-matched population.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Doenças Cardiovasculares/complicações , Neoplasias Pulmonares/cirurgia , Complicações Pós-Operatórias , Fatores Etários , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Doenças Cardiovasculares/mortalidade , Feminino , Humanos , Hipertensão/complicações , Modelos Logísticos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Seleção de Pacientes/ética , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Medição de Risco , Fumar/efeitos adversosRESUMO
BACKGROUND: Conflicting results have been obtained for the same operation for repair of coarctation of the aorta by different institutes. The purpose of this study was to assess the results of subclavian flap aortoplasty (SFA) alone, performed on 399 patients in a single institute between 1966 and 1995. METHODS: Data were collected retrospectively from the congenital cardiac surgical database at the institute. RESULTS: The median age at operation was 22 days (3 days-49 months). One hundred thirty-four patients had isolated coarctation while 265 children had complex coarctation. Maximum follow-up was 24 years (median, 14 years). Overall mortality over the whole duration of follow-up was 24.8%. Mortality for isolated coarctation at first intervention was 7.4% (operative mortality, 2.6%) while it was 12.8% for complex coarctation. At second intervention the mortality for isolated coarctation was 5%. For the second, third, and fourth interventions the mortality for complex coarctation was 25%, 25%, and 27%, respectively. The survival for isolated coarctation at 1, 5, 10, and 20 years was 94%, 93.2%, 92.4%, and 88.4%, respectively, while it was 74.6%, 66.3%, 63%, and 61.4%, respectively, for complex coarctation. Of the total patients, 15.3% had interventions for recoarctation. The incidence of recoarctation was 13.6% on those patients operated on in the first month of life, while it was 3.6% in older children. A percentage of 3.3% of patients continue to be hypertensive and require medication. There was a significant difference between the systolic blood pressure and anthropometric measurements between the arms. Despite this none of the patients complained of effect on lifestyle. CONCLUSIONS: Despite improved early results the long-term mortality for coarctation remains high. Mortality is higher for complex coarctation as compared with isolated procedures. The incidence of recoarctation after SFA at long term is acceptable and is higher in patients operated on in the first month of life. The overall incidence of hypertension is quite low. Patients remained normotensive when operated upon at the age of 0.9 months. The SFA, no doubt, effects the limb development; however it does not cause limitation in the lifestyle.