Determinação da frequência alélica de polimorfismos de nucleotídeo único e análise de sua aplicação clínica na monitorização de quimerismo pós transplante de células hematopoéticas
Bibliographic record
Abstract
The chimerism analysis has become a routine procedure after Allogeneic Hematopoietic Stem Cell transplantation (HSCT) for early detection of relapse or graft failure. In recent years, various techniques have been described to evaluate chimerism. The basic principle of its detection is the utilization of differences between recipient and donor genomes. The most commonly used method is based on amplification of small tandem repeats (STR), with sensitivity ranging from 1 to 5%. This method is useful for documenting graft, but it is not sufficient for the detection of minimal residual disease or early relapse; situations where medical intervention is urgently needed. Currently, the Single Nucleotide Polymorphisms (SNPs) appear to be useful as molecular markers for monitoring chimerism after HSCT due to their stability, specificity and can be analyzed using quantitative methods sensitive. Objectives: 1. To determine the frequency of 12 polymorphisms in the Brazilian population to use them as a basis in developing an informative panel for chimerism analysis. 2. To realize a comparative analysis of techniques, such as STR, TaqMan qPCR and LNA, for identification and quantification of SNPs performed on samples from Brazilian and Canadian populations. Methods: Analyses of allele frequencies of SNPs rs668, rs5984, rs1800734 and rs1799854 were performed by allele-specific PCR (ASO-PCR) in the Brazilian population. SNPs rs4880, rs2269848, rs163781, rs10757713, rs1432622, rs713503, rs2296600 and rs715463 were performed with TaqMan methodology (MGB) and LNA. Chimerism analysis techniques were performed used STR, TaqMan (MGB) and LNA. Results and Discussion: The SNPs analysis showed an allele frequency of approximately 50% for the ancestral allele for each SNP in the Brazilian and Canadian populations, suggesting this panel can be useful in the analysis of chimerism. However, more studies are needed to determine the informativity of this panel. Specific SNPs analysis using TaqMan technology (MGB) have proved to be useful in determining chimerism, despite initial difficulties for determine an informative panel. The LNA technology initially proved to be more sensitive and specific technique, however, its reproducibility was not effective. Typical assays for chimerism analysis are expensive and time consuming. Variations can occur between SNPs, so each SNP needs to be validated individually before its clinical application. TaqMan MGB technique was considered the best option to save time and money compared to LNA and STR. Conclusions: Despite its cost and time spent for its execution, STR is the gold standard test to monitor chimerism after HSCT mainly due to be commercially available. The studied SNPs appear to be useful as molecular markers for monitoring chimerism after HSCT due to the allele frequency presented. Genotyping using qPCR assay has the potential to reduce time and medical costs, important factors in developing countries, such as Brazil.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.002 | 0.003 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.003 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.003 | 0.001 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.002 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".