Method and device for detecting chromosomal aberrations

Abstract

A method and device for detecting chromosomal variation, the device comprises a sample-to-be-tested sequencing unit for sequencing a sample to be tested containing nucleic acid to obtain a sequencing result consisting of several sequencing data; a sample-to-be-tested correction unit for A normal data set is used to correct the sample to be tested; a segmentation unit is used to segment the corrected sequencing result to obtain several data fragments; and a detection unit is used to detect whether each data fragment is a copy number variation fragment. The application reduces the probability of missed detection of chromosomal abnormalities, reduces false positives and false negatives, has higher detection accuracy for chromosomal non-integrity and chromosomal copy number variation, and can detect smaller fragments under the condition of low fetal depth Chromosomal copy number variation.

Description

technical field [0001] The present invention relates to the field of chromosome detection. Background technique [0002] Non-invasive prenatal testing (NIPT) is a prenatal screening technology that has emerged in recent years. It is used to screen fetuses for trisomy 21, trisomy 18, and trisomy 13 in the first or second gestational weeks. The basic principle of the risk of chromosomal aneuploidy is to perform massively parallel sequencing of fetal cell-free DNA in the peripheral blood of pregnant women, and to analyze whether DNA sequencing signals on specific chromosomes are abnormally increased, so as to estimate the risk of fetal disease. Compared with traditional methods such as serological screening and ultrasound detection of fetal zona pellucida, non-invasive prenatal testing has a very high sensitivity (>99%) and a very low false positive rate (<0.5%), which can reduce unnecessary The number of invasive prenatal diagnoses and the number of missed tests can red...

AI Technical Summary

Problems solved by technology

[0016] (1) There are defects in data correction: when correcting the data, the above scheme adopts the strategy of correcting the same batch of samples. By default, the samples of the same batch are normal baseline samples. Correction

The disadvantage of this is that once the same chromosomal deletion / duplication exists in the same batch of samples, it will cause data correction errors, resulting in missed detection of chromosomal abnormal signals at this position

[0017] (2) It is impossible to solve the data bias caused by the experimental environment, reagents and sample characteristics among different batches of sequencing samples: because the above scheme adopts the same batch of sample correction strategy and ignores the differences between different batches of samples, so It will cause the corrected data to still be biased, that is, there will be false data enrichment or deletion in certain regions of the genome, resulting in false positive or false negative results

[0018] (3) The detection effect on sex chromosome abnormalities and mosaicism is not obvious: the above design is only designed to detect chromosome copy number variation, and only evaluates the detection performance of chromosome copy number variation, and has no effect on the detection of sex chromosome abnormalities and mosaicism Dedicated design and evaluation

[0019] (4) The ability to detect chromosomal copy number variation for small data (for example, less than 10Mb) is not strong: according to the simulated experimental data, the detection accuracy of the above-mentioned scheme for chromosomal copy number variation is above 10Mb, and a high proportion of free nucleic acid is required (10%) (Chen S, Lau TK, Zhang C, et al. A method for noninvasive detection of fetal large deletions / duplications by low coverage massively parallel sequencing. Prenat Diagn. 2013 Jun; 33(6): 584-90.), For chromosome copy number variation less than 10Mb or lower proportion of free nucleic acid, the detection rate will be greatly reduced

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