CN113270138A - Method for enriching fetal free DNA for analyzing copy number variation based on bioinformatics - Google Patents
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Abstract
The invention discloses a method for enriching fetal free DNA for analyzing copy number variation based on bioinformatics. The invention selectively selects short segment reads which are mainly from fetuses and have both ends compared with a reference genome, calculates the fetal DNA content by calculating the ratio of the number of normalized sex chromosome reads of different segment lengths to the number of total autosomal reads, and selects the length range of free DNA segments with the highest fetal DNA content to perform subsequent aneuploidy and CNV analysis. The invention can improve the concentration ratio of the DNA of the fetus, and greatly improves the accuracy of the application of analyzing the aneuploidy of the chromosome of the fetus, the copy number abnormality of the chromosome fragment and the like.
Description
Technical Field
The invention belongs to the field of noninvasive prenatal screening application biological information data analysis based on NGS sequencing, and particularly relates to an analysis method for enriching fetal free DNA for copy number variation based on bioinformatics.
Background
In 1997, Denise Lo, university of Chinese in hong Kong, discovered that free DNA fragments from fetuses were present in the blood, with an average content of approximately 13% of the total free DNA content in maternal blood. By separating and extracting free DNA fragments in the peripheral blood of pregnant women with more than 12 weeks of pregnancy and adopting a large-scale parallel sequencing method, the method can accurately detect chromosome and fragment copy number abnormality, sex judgment, monogenic disease screening and the like of fetuses.
Currently, fetal free DNA enrichment is mainly carried out by an electrophoretic separation method or an experimental method of magnetic bead enrichment. However, because the content of free DNA fragments in the fetus is extremely low, it is difficult to separate free DNA fragments with different lengths, and the sample loss is caused. The two enrichment methods also increase the complexity of the experiment and prolong the library construction time period, and the data generated by the two methods can increase the redundancy of reads on the alignment, and meanwhile, the distribution uniformity of the reads on the reference genome is poor, so that the false positive rate can be increased.
Disclosure of Invention
The invention aims to overcome the defects of the prior art, consider that the sequencing quantity is increased in a certain range along with the reduction of the next generation sequencing cost, extract DNA molecules from a fetus as far as possible, and improve the fetal DNA proportion through a biological information screening method, thereby having higher accuracy for analyzing fetal chromosome aneuploidy and chromosome fragment CNV, simultaneously reducing the proportion of re-loading or re-blood collection caused by insufficient fetal DNA content, and having higher qualified rate of detected samples, thereby further reducing the cost.
Since fetal plasma free DNA is much shorter than maternal free DNA fragments, we calculated fragment length distribution based on the position of two reads aligned to the reference genome by double-ended sequencing at the sequencing data level without changing the experimental DNA extraction and banking methods. Based on the fragment length distribution, selecting 50-200, 50-210, 50-220, 50-230, 50-240 and 50-250 by taking 10bp as step; 60-200, 60-210, 60-220, 60-230, 60-240, 60-250; …,120-200,120-210,120-220,120-230,120-240,120-250 … DNA fragments are positioned in the reads in the regions, the reads number and GC in each chromosome and each sliding window are calculated for each sample, and the reads number of each sample is subjected to homogenization treatment by using the total comparison to the reads number of the autosome.
Calculating the fetal DNA content by calculating the ratio of the number of normalized sex chromosome reads in the total number of autosomal chromosomes reads of different fragment lengths, and selecting the free DNA fragment length range with the highest fetal DNA content for subsequent aneuploidy and CNV analysis
For autosome and female fetus X chromosome, subtracting the normal copy number by the calculated copy number of CNV by 2, and multiplying by 100% to obtain the chimeric ratio (MosRatio) of the CNV; for the X chromosome and the Y chromosome of a male fetus, the calculated copy number of the CNV is subtracted by 1 of the normal copy number, and the CNV is multiplied by 100% to obtain the chimeric ratio of the CNV. If the chimerism ratio is less than 50%, it is generally reflected by the magnitude of the fetal DNA content, which is positively correlated with the fetal DNA content. If the current sample has more CNVs (possibly containing benign and pathogenic CNVs), the median of the chimerism ratio of all CNVs is approximately comparable to the fetal DNA content.
Specific alternatives of the invention:
the invention discloses an analysis method for enriching free DNA of a fetus based on bioinformatics, which comprises the following steps:
1) performing fault-tolerant alignment on double-end reads to a reference genome, and recording the chromosomes, coordinate positions and GC of the reads aligned to the reference genome;
2) preserving reads with both ends aligned to the reference genome and insert size within 1 kb; the insert size refers to the distance of a pair of ends aligned to reads on a reference genome;
3) making a frequency distribution map of insert size within the range of 50-500 bp to obtain a fragment distribution rule;
4) respectively selecting reads with insert size in a set area by taking the set bp as step; calculating the reads number and GC on each chromosome and in each sliding window for each sample, and carrying out homogenization treatment on the reads number of each sample to the reads number of the autosome by using the total comparison;
5) calculating the fetal DNA content of the proportion of the normalized reads in the comparison of the X chromosomes in different insert size fragment distribution ranges of each sample to the reads of the total normalized autosomes, and selecting the insert size fragment distribution range with the highest fetal DNA content as the data of the subsequent analysis.
The invention further discloses a method for analyzing copy number variation, which comprises the following steps:
a. obtaining the distribution range of insert size fragments with the highest fetal DNA content as analysis data based on the analysis method for enriching the free DNA of the fetus based on the bioinformatics;
b. the selected reads are set as bin size and step, and the number of the reads and GC in each sliding window (bin) are respectively calculated;
c. making a dot diagram of all read counts and GCs in a single sample, wherein the horizontal axis is GC, the vertical axis is RC (read count), fitting a curve by using a LOESS regression model, bringing the GC in each bin into the fitted curve to obtain a fitted predicted value P, taking the median M of the RCs of all sliding windows, wherein a correction factor F is the ratio of P to M, and multiplying the RC of each bin by a correction factor F corresponding to each bin to obtain corrected RC (RCcorrected);
d. taking the natural logarithm of the ratio of RCcorrected in each bin of the sample to be detected to RCcorrected in each bin of more than 10 samples of the same batch, the same library construction method, the same sequencing platform and the same sex to obtain the log2ratio of each bin;
e. each bin on each chromosome is fragmented, resulting in each fragment (seg) and its corresponding log2ratio data.
f. Obtaining the copy number CN of each segment of the chromosome;
g. obtaining the MosRatio of the chimeric ratio by the absolute value of the difference value between CN and 2 of each fragment;
h. filtering out fragments with MosRatio less than 0.05, and keeping the fragments with MosRatio more than 0.05 and fragment length more than 1M as the final result of the fetal-derived CNV.
The invention solves the problem that the fetal chromosome aneuploidy or fetal chromosome fragment copy number abnormality cannot be accurately detected due to low fetal DNA concentration in the field of noninvasive prenatal screening. The invention relates to optimization of a data analysis layer. The method of the invention is applied to test the comparison of the enrichment without fragment screening and the enrichment with fragment screening respectively. The fetal DNA short fragment enrichment based on the biological information layer of the invention has the advantages that the average fetal DNA content is improved by about 1.5 percent, the fetal DNA content is obviously reduced by less than 4 percent of the threshold value, the detection success rate is greatly increased, and the fetal aneuploidy and CNV false negative are obviously reduced; and the fetal source CNV and the maternal CNV are obviously distinguished, false positives (background noise signals) caused by non-specific comparison or other interference conditions are obviously reduced, and the detection specificity is obviously improved.
Compared with the free DNA fragment length screening without the biogenesis level in the prior art, the fetal free DNA content of the fragment screening is improved by about 1.5 percent. The false positive of CNV is reduced obviously, and the specificity of fetal CNV is improved.
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FIG. 1 is a schematic flow diagram of the process of the present invention.
FIG. 2 is a graph of the distribution of free DNA fragment lengths of all pairs of reads in the example plotted as a density distribution; each line represents the free DNA fragment length distribution for each sample;
FIG. 3 is a graph showing the results of the present invention on the increase in fetal free DNA content compared to the prior art protocol;
fig. 4 is a schematic diagram of the specificity improvement of fetal CNV; left shows fetal CNV chimerism proportion distribution without enrichment, right shows fetal CNV chimerism proportion distribution after short fragment fetal DNA enrichment.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
FIG. 1 is a schematic flow chart of the method of the present invention, which is summarized as follows:
1) performing double-end sequencing on a sequencing data level, performing fault-tolerant comparison on double-end reads to a reference genome, and recording the chromosomes, coordinate positions and GC of the reads compared to the reference genome;
2) preserving reads with both ends aligned to the reference genome and insert size within 1 kb; the insert size refers to the distance of a pair of ends aligned to reads on a reference genome;
3) making a frequency distribution map of insert size within the range of 50-500 bp to obtain a fragment distribution rule;
4) respectively selecting reads with insert size in a set area by taking the set bp as step; calculating the reads number and GC on each chromosome and in each sliding window for each sample, and carrying out homogenization treatment on the reads number of each sample to the reads number of the autosome by using the total comparison;
5) calculating the fetal DNA content of the proportion of the normalized reads in the comparison of the X chromosomes in different insert size fragment distribution ranges of each sample to the reads of the total normalized autosomes, and selecting the insert size fragment distribution range with the highest fetal DNA content as the data of the subsequent analysis.
The reads selected in step 5 of the present invention were analyzed for fetal chromosome 13, 18, 21 aneuploidy, and the calculation method was also referred to in this document (https:// pubmed. ncbi. nlm. nih. gov/23299662 /).
The reads selected in step 5 of the invention can also be used for analyzing fetal aneuploidy and copy number variation, and the reference steps are as follows:
b. the selected reads are set as bin size and step, and the number of the reads and GC in each sliding window (bin) are respectively calculated;
c. making a dot diagram of all read counts and GCs in a single sample, wherein the horizontal axis is GC, the vertical axis is RC (read count), fitting a curve by using a LOESS regression model, bringing the GC in each bin into the fitted curve to obtain a fitted predicted value P, taking the median M of the RCs of all sliding windows, wherein a correction factor F is the ratio of P to M, and multiplying the RC of each bin by a correction factor F corresponding to each bin to obtain corrected RC (RCcorrected);
d. taking the natural logarithm of the ratio of RCcorrected in each bin of the sample to be detected to RCcorrected in each bin of more than 10 samples of the same batch, the same library construction method, the same sequencing platform and the same sex to obtain the log2ratio of each bin;
e. each bin on each chromosome is fragmented, resulting in each fragment (seg) and its corresponding log2ratio data.
f. Obtaining the copy number CN of each segment of the chromosome;
g. obtaining the MosRatio of the chimeric ratio by the absolute value of the difference value between CN and 2 of each fragment;
h. filtering out fragments with MosRatio less than 0.05, and keeping the fragments with MosRatio more than 0.05 and fragment length more than 1M as the final result of the fetal-derived CNV.
The present invention will be further described with reference to the following specific examples.
In this example, 284 NIPT data of a double-ended sequencing mode of an Illumina NextSeq CN500 model sequencer were aligned to a reference genome (hg19 version) in a non-fault-tolerant manner, reads with both ends aligned to the reference genome were selected, free DNA fragment length distribution was calculated according to the distance between coordinates of both ends of aligned pairs of reads on the reference genome, and density distribution curves were prepared from the free DNA fragment length distribution data of all pairs of reads. As shown in fig. 2.
Based on the distribution rule of the graph, selecting 50-200 bp, 50-210 bp, 50-220 bp, 50-230 bp, 50-240 bp and 50-250 bp respectively by taking 10bp as step; 60-200, 60-210, 60-220, 60-230, 60-240, 60-250; …,120, 200,120, 210,120, 220,120, 230,120, 250 free DNA fragments are positioned in the reads in the regions, the reads number and GC in each chromosome and each sliding window are calculated for each sample, and the reads number of each sample is normalized by the total comparison to the reads number of the autosome.
Calculating the fetal DNA content according to the proportion of the normalized reads in the comparison of X chromosomes of different insert size fragment distributions of each sample to the reads of the total normalized autosomes, wherein the calculation of the fetal DNA content can be referred to in the literature (https:// pubmed. ncbi. nlm. nih. gov/23299662), and selecting the insert size fragment distribution with the highest fetal DNA content as the data of the subsequent analysis. The aneuploidy of chromosome 13, 18 and 21 of fetus was analyzed by calculating the aneuploidy of chromosome for each sample using other samples of the same lot as controls.
Aiming at CNV analysis, the invention respectively calculates the number of reads in each sliding window (bin) and GC according to 100kb bin size and 20kb step
Making a dot diagram of all read counts and GCs (accurate to a decimal point) in a single sample, wherein the horizontal axis is GC, the vertical axis is RC (read count), fitting a curve by using an LOESS regression model, bringing the GC in each bin into the fitting curve to obtain a fitting predicted value (P), taking the median (M) of the RCs of all sliding windows, wherein a correction factor (F) is the ratio of P to M, and multiplying the RC of each bin by a correction factor F corresponding to each bin to obtain corrected RC (RCcorrected)
Taking the natural logarithm of the ratio of RCcorrected in each bin of the sample to be detected to RCcorrected in each bin of more than 10 samples of the same batch, the same library construction method, the same sequencing platform and the same sex to obtain the log2ratio of each bin
Each bin on each chromosome is fragmented using the Circular Binary Segmentation (CBS) algorithm, resulting in each fragment (seg) and its corresponding log2ratio data.
For female test samples, log2ratio of each fragment is raised to a power of 2 and then multiplied by 2, i.e., 2X 2 (log2ratio), to yield Copy Numbers (CN) for each fragment of chromosomes 1-22 and X. For the method for calculating the copy number of the fragment on the chromosome 1-22 of the male test sample to be consistent with that of the female, the copy number of the X chromosome and the Y chromosome is calculated to be 2^ (log2 ratio).
The absolute value of the difference between CN and 2 for each fragment was used to obtain the MosRatio (mosritio).
Filtering out fragments with MosRatio less than 0.05, and keeping the fragments with MosRatio more than 0.05 and fragment length more than 1M as the final result of the fetal-derived CNV.
Compared with the free DNA fragment length screening without the messenger level, the content of the free DNA of the fetus subjected to the fragment screening is improved by about 1.5 percent (figure 3). The false positives of CNVs were significantly reduced and the specificity of fetal CNVs was improved (fig. 4, left side shows fetal CNV chimerism proportion distribution without enrichment and right side shows fetal CNV chimerism proportion distribution after short-fragment fetal DNA enrichment).
Claims (6)
1. An analysis method for enriching fetal free DNA based on bioinformatics, which is characterized by comprising the following steps:
1) performing fault-tolerant alignment on double-end reads to a reference genome, and recording the chromosomes, coordinate positions and GC of the reads aligned to the reference genome;
2) preserving reads with both ends aligned to the reference genome and insert size within 1 kb; the insert size refers to the distance of a pair of ends aligned to reads on a reference genome;
3) making a frequency distribution map of insert size within the range of 50-500 bp to obtain a fragment distribution rule;
4) respectively selecting reads with insert size in a set area by taking the set bp as step; calculating the reads number and GC on each chromosome and in each sliding window for each sample, and carrying out homogenization treatment on the reads number of each sample to the reads number of the autosome by using the total comparison;
5) calculating the fetal DNA content of the proportion of the normalized reads in the comparison of the X chromosomes in different insert size fragment distribution ranges of each sample to the reads of the total normalized autosomes, and selecting the insert size fragment distribution range with the highest fetal DNA content as the data of the subsequent analysis.
2. The bioinformatics-based fetal free DNA enrichment assay method according to claim 1, wherein the step 4) is specifically:
selecting 50-200, 50-210, 50-220, 50-230, 50-240 and 50-250 respectively by taking 10bp as step; 60-200, 60-210, 60-220, 60-230, 60-240, 60-250; …,120, 200,120, 210,120, 220,120, 230,120, 250 free DNA fragments are positioned in the reads in the regions, the reads number and GC in each chromosome and each sliding window are calculated for each sample, and the reads number of each sample is subjected to homogenization treatment by using the total comparison to the reads number of the autosome.
3. A method for enriching fetal free DNA for copy number variation analysis based on bioinformatics, comprising the steps of:
a. obtaining a distribution range of insert size fragments with the highest fetal DNA content as analysis data based on the method of claim 1 or 2;
b. the selected reads are set as bin size and step, and the number of the reads and GC in each sliding window (bin) are respectively calculated;
c. making a dot diagram of all read counts and GCs in a single sample, wherein the horizontal axis is GC, the vertical axis is RC (read count), fitting a curve by using a LOESS regression model, bringing the GC in each bin into the fitted curve to obtain a fitted predicted value P, taking the median M of the RCs of all sliding windows, wherein a correction factor F is the ratio of P to M, and multiplying the RC of each bin by a correction factor F corresponding to each bin to obtain corrected RC (RCcorrected);
d. taking the natural logarithm of the ratio of RCcorrected in each bin of the sample to be detected to RCcorrected in each bin of more than 10 samples of the same batch, the same library construction method, the same sequencing platform and the same sex to obtain the log2ratio of each bin;
e. each bin on each chromosome is fragmented, resulting in each fragment (seg) and its corresponding log2ratio data.
f. Obtaining the copy number CN of each segment of the chromosome;
g. obtaining the MosRatio of the chimeric ratio by the absolute value of the difference value between CN and 2 of each fragment;
h. filtering out fragments with MosRatio less than 0.05, and keeping the fragments with MosRatio more than 0.05 and fragment length more than 1M as the final result of the fetal-derived CNV.
4. The method for analyzing copy number variation of claim 3, wherein in step b, the numbers of reads and GC in each sliding window are calculated according to 100kb bin size and 20kb step.
5. The method for analyzing copy number variation of claim 3, wherein in step f, for female samples to be tested, the log2ratio of each fragment is raised to a power of 2 and then multiplied by 2, i.e. 2X 2 (log2ratio), to obtain the copy number CN of each fragment of chromosomes 1-22 and X.
6. The method for analyzing copy number variation as claimed in claim 3, wherein in step f, log2ratio of each segment is raised to a power of 2 and then multiplied by 2, i.e. 2X 2 (log2ratio), and copy numbers of X and Y chromosomes are calculated to be 2 (log2ratio) for the male test sample, so as to obtain copy numbers CN of each segment of chromosomes 1-22, X and Y chromosomes.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106591451A (en) * | 2016-12-14 | 2017-04-26 | 北京贝瑞和康生物技术股份有限公司 | Method for detecting content of fetal-free DNA, and apparatus for enforcing method |
| WO2017093561A1 (en) * | 2015-12-04 | 2017-06-08 | Genesupport Sa | Method for non-invasive prenatal testing |
| US20170220735A1 (en) * | 2016-02-03 | 2017-08-03 | Verinata Health, Inc. | Using cell-free dna fragment size to determine copy number variations |
| CN107133495A (en) * | 2017-05-04 | 2017-09-05 | 北京医院 | A kind of analysis method and analysis system of aneuploidy biological information |
| CN108573125A (en) * | 2018-04-19 | 2018-09-25 | 上海亿康医学检验所有限公司 | Method for detecting genome copy number variation and device comprising same |
-
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- 2021-04-13 CN CN202110397074.3A patent/CN113270138B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017093561A1 (en) * | 2015-12-04 | 2017-06-08 | Genesupport Sa | Method for non-invasive prenatal testing |
| US20170220735A1 (en) * | 2016-02-03 | 2017-08-03 | Verinata Health, Inc. | Using cell-free dna fragment size to determine copy number variations |
| CN106591451A (en) * | 2016-12-14 | 2017-04-26 | 北京贝瑞和康生物技术股份有限公司 | Method for detecting content of fetal-free DNA, and apparatus for enforcing method |
| CN107133495A (en) * | 2017-05-04 | 2017-09-05 | 北京医院 | A kind of analysis method and analysis system of aneuploidy biological information |
| CN108573125A (en) * | 2018-04-19 | 2018-09-25 | 上海亿康医学检验所有限公司 | Method for detecting genome copy number variation and device comprising same |
Non-Patent Citations (2)
| Title |
|---|
| HUDECOVA, I., ET AL.: "Maternal plasma fetal DNA fractions in pregnancies withlow and high risks for fetal chromosomal aneuploidies", 《PLOS ONE》, vol. 9, no. 2, XP055662324, DOI: 10.1371/journal.pone.0088484 * |
| 梅瑾;王昊;王敏;何茶英;: "二代测序技术在流产物染色体拷贝数改变检测中的应用", 浙江医学, no. 02 * |
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