Patent ID: 11923046
Assignee: THE CHINESE UNIVERSITY OF HONG KONG
Field: Computer technology (Electrical engineering)
Classification: CPC G | IPC G

Claim 20:
21. A method of identifying microamplifications or microdeletions in a genome of a fetus by analyzing a biological sample obtained from a female subject pregnant with the fetus, the biological sample including cell-free DNA from the fetus and from the female subject, the method comprising:
obtaining a blood sample from the pregnant female;
extracting plasma or serum from the blood sample to obtain the biological sample;
obtaining, by massively parallel sequencing, one or more sequence tags for each of a plurality of DNA fragments in the biological sample;
receiving the one or more sequence tags;
determining, with a computer system, genomic positions for the sequence tags in a reference genome, wherein determining genomic positions for the sequence tags includes aligning the sequence tags to a reference genome;
for each of a plurality of genomic regions:
determining, with the computer system, a respective amount of DNA fragments within the genomic region from sequence tags having genomic positions within the genomic region;
normalizing the respective amount to obtain a respective density; and
comparing the respective density to a reference density to identify whether the respective density is statistically different from the reference density, wherein the genomic regions are non-overlapping;

determining whether any of the genomic regions identified to have a respective density statistically different from the reference density is consecutive with another genomic region identified to have a respective density statistically different from the reference density, wherein each of the plurality of genomic regions is from 100 kb to 10 Mb;
when at least N first genomic regions identified to have respective densities statistically higher than the reference density are consecutive, identifying the consecutive first genomic regions as a microamplification in the fetus, N being an integer equal to or greater than three;
when at least N second genomic regions identified to have respective densities statistically lower than the reference density are consecutive, identifying the consecutive second genomic regions as a microdeletion in the fetus,
wherein the method is capable of achieving a diagnostic sensitivity of 95% for the plurality of DNA fragments equal to 125 million fragments when each of the plurality of genomic regions is 1 Mb.