Abordagem computacional para detecção de aneuploidias fetais

Abstract

The discovery of the cell free fetal DNA (cffDNA) in maternal plasma and serum allowed the development of new test for fetal disorders in a non-invasive way (NIPT). The detection of the cffDNA is possible around the seventh week, and its concentration increases along the gestational period. Those characteristics allow the early identification of many fetal issues and the palliative actions. Regarding the Next-Generation Sequencing (NGS) tech, several methods has been described on literature asserting a consistent sensibility to detection of aneuploidy cases as Down, Edward and Patau syndromes. We propose a method in sílico, CAADy (Computational Approach for Detection of Fetal Aneuploidies), a strategy to detection of fetal aneuploidies. That method removes outliers which can come from diferent technologies of sequencing and it will allow the identification of genetic diseases of chromosomal origin. In this study was used the method of z-score with internal reference calculated by median absolute deviation (MAD) for identify the cases of trisomy of chromosomes 13, 18 and 21 (2, 12 and 16 cases, respectively) included in the 903 samples of cffDNA availables in the SRA portal (http://www.ncbi.nlm.nih.gov/sra/SRA047257). We detected all cases of trisomies and with 100% of sensitivity and specificity. The confirmation of results observed in sílico were based on the karyotype. Therefore, our methodology was presented as great for the detection of trisomies.