Clinical and genetic ancestry profile of a large multi-centre sickle cell disease cohort in Brazil.

Approximately 3500 children with sickle cell disease (SCD) are born in Brazil each year, but the burden of SCD morbidity is not fully characterised. A large, multi-centre cohort was established to characterise clinical outcomes in the Brazilian SCD population and create the infrastructure to perform genotype-phenotype association studies. Eligible patients were randomly selected from participating sites and recruited at routine visits. A biorepository of blood samples was created and comprehensive demographic and clinical outcome data were entered in a centralized electronic database. Peripheral blood genome-wide single nucleotide polymorphism (SNP) genotyping was performed using a customized Transfusion Medicine (TM) Array. A total of 2795 participants at six Brazilian sites were enrolled between 2013 and 2015. The cohort included slight predominance of children <18 years (55·9%) and females (53·0%). Haemoglobin (Hb) SS was the most common SCD genotype (70·7%), followed by HbSC (23%), Sß0 (3·0%) and Sß+ (2·9%). SNP data from the TM Array were analysed to evaluate the genetic ancestry of the cohort and revealed significant admixture among the population. Demographics and clinical complications, stratified by age and SCD genotype, are summarized and future studies in this cohort are discussed.

Molecular description of α-keto-based inhibitors of cruzain with activity against Chagas disease combining 3D-QSAR studies and molecular dynamics.

In this work, a group of α-keto-based inhibitors of the cruzain enzyme with anti-chagas activity was selected for a three-dimensional quantitative structure-activity relationship study (3D-QSAR) combined with molecular dynamics (MD). Firstly, statistical models based on Partial Least Square (PLS) regression were developed employing comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) descriptors. Validation parameters (q2 and r2 )for the models were, respectively, 0.910 and 0.997 (CoMFA) and 0.913 and 0.992 (CoMSIA). In addition, external validation for the models using a test group revealed r2pred  = 0.728 (CoMFA) and 0.971 (CoMSIA). The most relevant aspect in this study was the generation of molecular fields in both favorable and unfavorable regions based on the models developed. These fields are important to interpret modifications necessary to enhance the biological activities of the inhibitors. This analysis was restricted considering the inhibitors in a fixed conformation, not interacting with their target, the cruzain enzyme. Then, MD was employed taking into account important variables such as time and temperature. MD helped describe the behavior of the inhibitors and their properties showed similar results as those generated by QSAR-3D study.

Methodological Guidelines for Reducing the Complexity of Data Warehouse Development for Transactional Blood Bank Systems.

Over time, data warehouse (DW) systems have become more difficult to develop because of the growing heterogeneity of data sources. Despite advances in research and technology, DW projects are still too slow for pragmatic results to be generated. Here, we address the following question: how can the complexity of DW development for integration of heterogeneous transactional information systems be reduced? To answer this, we proposed methodological guidelines based on cycles of conceptual modeling and data analysis, to drive construction of a modular DW system. These guidelines were applied to the blood donation domain, successfully reducing the complexity of DW development.

Analysis of donor deferral at three blood centers in Brazil.

BACKGROUND: The safety of the blood supply is ensured through several procedures from donor selection to testing of donated units. Examination of the donor deferrals at different centers provides insights into the role that deferrals play in transfusion safety. STUDY DESIGN AND METHODS: A cross-sectional descriptive study of prospective allogeneic blood donors at three large blood centers located in São Paulo, Belo Horizonte, and Recife, Brazil, from August 2007 to December 2009 was conducted. Deferrals were grouped into similar categories across the centers, and within each center frequencies out of all presentations were determined. RESULTS: Of 963,519 prospective blood donors at the three centers, 746,653 (77.5%) were accepted and 216,866 (22.5%) were deferred. Belo Horizonte had the highest overall deferral proportion of 27%, followed by Recife (23%) and São Paulo (19%). Females were more likely to be deferred than males (30% vs. 18%, respectively). The three most common deferral reasons were low hematocrit or hemoglobin, medical diagnoses, and higher-risk behavior. CONCLUSION: The types and frequencies of deferral vary substantially among the three blood centers. Factors that may explain the differences include demographic characteristics, the order in which health history and vital signs are taken, the staff training, and the way deferrals are coded by the centers among other policies. The results indicate that blood donor deferral in Brazil has regional aspects that should be considered when national policies are developed.

Blood transfusion utilization and recipient survival at Hospital das Clinicas in São Paulo, Brazil.

BACKGROUND: The characteristics of blood recipients including diagnoses associated with transfusion and posttransfusion survival are unreported in Brazil. The goals of this analysis were: 1) to describe blood utilization according to clinical diagnoses and patient characteristics and 2) to determine the factors associated with survival of blood recipients. STUDY DESIGN AND METHODS: A retrospective cross-sectional analysis was conducted on all inpatients in 2004. Data came from three sources: The first two files consist of data about patient characteristics, clinical diagnosis, and transfusion. Analyses comparing transfused and nontransfused patients were conducted. The third file was used to determine survival recipients up to 3 years after transfusion. Logistic regression was conducted among transfused patients to examine characteristics associated with survival. RESULTS: In 2004, a total of 30,779 patients were admitted, with 3835 (12.4%) transfused. These patients had 10,479 transfusions episodes, consisting of 39,561 transfused components: 16,748 (42%) red blood cells, 15,828 (40%) platelets (PLTs), and 6190 (16%) plasma. The median number of components transfused was three (range, 1-656) per patient admission. Mortality during hospitalization was different for patients whose admissions included transfusion or not (24% vs. 4%). After 1 year, 56% of transfusion recipients were alive. The multivariable model of factors associated with mortality after transfusion showed that the most significant factors in descending order were hospital ward, increasing age, increasing number of components transfused, and type of components received. CONCLUSION: Ward and transfusion are markers of underlying medical conditions and are associated with the probability of survival. PLT transfusions are common and likely reflect the types of patients treated. This comprehensive blood utilization study, the first of its kind in Brazil, can help in developing transfusion policy analyses in South America.

A rigorous approach to facilitate and guarantee the correctness of the genetic testing management in human genome information systems.

BACKGROUND: Recent medical and biological technology advances have stimulated the development of new testing systems that have been providing huge, varied amounts of molecular and clinical data. Growing data volumes pose significant challenges for information processing systems in research centers. Additionally, the routines of genomics laboratory are typically characterized by high parallelism in testing and constant procedure changes. RESULTS: This paper describes a formal approach to address this challenge through the implementation of a genetic testing management system applied to human genome laboratory. We introduced the Human Genome Research Center Information System (CEGH) in Brazil, a system that is able to support constant changes in human genome testing and can provide patients updated results based on the most recent and validated genetic knowledge. Our approach uses a common repository for process planning to ensure reusability, specification, instantiation, monitoring, and execution of processes, which are defined using a relational database and rigorous control flow specifications based on process algebra (ACP). The main difference between our approach and related works is that we were able to join two important aspects: 1) process scalability achieved through relational database implementation, and 2) correctness of processes using process algebra. Furthermore, the software allows end users to define genetic testing without requiring any knowledge about business process notation or process algebra. CONCLUSIONS: This paper presents the CEGH information system that is a Laboratory Information Management System (LIMS) based on a formal framework to support genetic testing management for Mendelian disorder studies. We have proved the feasibility and showed usability benefits of a rigorous approach that is able to specify, validate, and perform genetic testing using easy end user interfaces.

Demographic profile of blood donors at three major Brazilian blood centers: results from the International REDS-II study, 2007 to 2008.

BACKGROUND: The profile of blood donors changed dramatically in Brazil over the past 20 years, from remunerated to nonremunerated and then from replacement to community donors. Donor demographic data from three major blood centers establish current donation profiles in Brazil, serving as baseline for future analyses and tracking longitudinal changes in donor characteristics. STUDY DESIGN AND METHODS: Data were extracted from the blood center, compiled in a data warehouse, and analyzed. Population data were obtained from the Brazilian census. RESULTS: During 2007 to 2008, there were 615,379 blood donations from 410,423 donors. A total of 426,142 (69.2%) were from repeat (Rpt) donors and 189,237 (30.8%) were from first-time (FT) donors. Twenty percent of FT donors returned to donate in the period. FT donors were more likely to be younger, and Rpt donors were more likely to be community donors. All were predominantly male. Replacement donors still represent 50% of FT and 30% of Rpt donors. The mean percentage of the potentially general population who were donors was approximately 1.2% for the three centers (0.7, 1.5, and 3.1%). Adjusting for the catchment's area, the first two were 2.1 and 1.6%. CONCLUSIONS: Donors in the three Brazilian centers tended to be younger with a higher proportion of males than in the general population. Donation rates were lower than desirable. There were substantial differences in sex, age, and community/replacement status by center. Studies on the safety, donation frequencies, and motivations of donors are in progress to orient efforts to enhance the availability of blood.

DBCollHIV: a database system for collaborative HIV analysis in Brazil.

We developed a database system for collaborative HIV analysis (DBCollHIV) in Brazil. The main purpose of our DBCollHIV project was to develop an HIV-integrated database system with analytical bioinformatics tools that would support the needs of Brazilian research groups for data storage and sequence analysis. Whenever authorized by the principal investigator, this system also allows the integration of data from different studies and/or the release of the data to the general public. The development of a database that combines sequences associated with clinical/epidemiological data is difficult without the active support of interdisciplinary investigators. A functional database that securely stores data and helps the investigator to manipulate their sequences before publication would be an attractive tool for investigators depositing their data and collaborating with other groups. DBCollHIV allows investigators to manipulate their own datasets, as well as integrating molecular and clinical HIV data, in an innovative fashion.

Multi-character population study of the vir subtelomeric multigene superfamily of Plasmodium vivax, a major human malaria parasite.

Plasmodium vivax, the most widely distributed human malaria parasite, contains the subtelomeric multigene vir superfamily corresponding to circa 10% of its coding genome. In this work, we used a multi-character strategy to study the vir gene repertoire circulating in natural parasite populations obtained directly from 32 human patients from endemic regions of Brazil and Sri Lanka. Cladistic analysis confirmed the existence of vir subfamilies, which varied in size and allele polymorphisms. Moreover, different motifs, protein domain, and secondary structures were predicted for each subfamily. Of importance, not all vir sequences possess a recognizable Pexel motif recently shown to be important, though not essential, signal for transportation to the cell membrane of infected red blood cells. Furthermore, subfamilies A and D display common structural features with the recently described P. falciparum SURFIN and Pfmc-2tm subtelomeric multigene families. These results suggest that VIR proteins can have different subcellular localizations and functions. This is the first study on a population level of the P. vivax vir subtelomeric multigene superfamily.

Trends in antiretroviral drug resistance and clade distributions among HIV-1--infected blood donors in Sao Paulo, Brazil.

BACKGROUND: We analyzed rates of drug resistance mutations in antiretroviral-naive São Paulo blood donors with recently acquired or established HIV-1 infections and characterized clade diversity in this population. METHODS: Six hundred forty-eight seropositive blood donor specimens were identified at the Blood Center of São Paulo between July 1998 and March 2002. To discriminate recent infections, samples were subjected to the standardized testing algorithm for recent HIV seroconversion (less-sensitive enzyme immunoassay) testing algorithm. There were 531 samples with a sufficient volume of serum to attempt polymerase chain reaction (PCR) and viral sequencing; 341 (64%) samples yielded a PCR product that could be sequenced for the reverse transcriptase and protease genes. Mutations were analyzed using the 2005 International AIDS Society mutation list. RESULTS: Of 341 specimens successfully analyzed, 21 (6.3%; 95% confidence interval [CI]: 3.9% to 9.3%) had drug-resistant mutations. The proportion of resistant strains was 12.7% (95% CI: 5.2% to 24.5%) among recently infected individuals compared with 5.0% (95% CI: 2.8% to 8.2%) among those with long-standing infections (P = 0.03). No change in the proportion of drug-resistant strains was observed among recently infected donor samples from the first half of the study period (4 of 32 samples) as compared with the second half (3 of 23 samples; P = 0.95). Of the 341 samples, 277 (81.2%) were classified as subtype B, 25 (7.3%) as subtype F1, 13 (3.8%) as subtype C, and 26 (7.6%) as recombinant strains. The distribution of HIV-1 subtypes was similar among recent and long-standing infected individuals and over time. CONCLUSIONS: The prevalence of drug-resistant mutations among newly diagnosed persons in São Paulo city is low and similar to what has been described in Europe and the United States. Although HIV-1 subtype B remains predominant, subtypes F and C and recombinant forms are present in substantial proportions in infected donors.

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.