Size-based genomic analysis

A computer program product comprising a non-transitory computer readable medium storing a plurality of instructions for controlling a processor to perform an operation for performing prenatal diagnosis of a sequence imbalance in a biological sample obtained from a female subject pregnant with a fetus, wherein the biological sample includes nucleic acid molecules that are part of nucleic acid sequences, the biological sample including nucleic acid molecules from the fetus and the female subject, the instructions comprising:

• for each of a plurality of the nucleic acid molecules in the biological sample:
• measuring a size of the nucleic acid molecule;
• identifying which nucleic acid sequence the nucleic acid molecule is derived from;
• determining a size distribution of the nucleic acid molecules corresponding to a first sequence;
• and
• based on the determined size distribution, determining a classification of whether a sequence imbalance exists for the first sequence.

A method for performing prenatal diagnosis of a fetal chromosomal aneuploidy in a biological sample obtained from a female subject pregnant with a fetus, wherein the biological sample includes nucleic acid molecules from the fetus and the female subject, the method comprising:

• for each of a plurality of the nucleic acid molecules in the biological sample:
• measuring a size of the nucleic acid molecule;
• identifying which chromosome the nucleic acid molecule is derived from;
• for each of a plurality of chromosomes, calculating, using a computer system, a statistical value from the sizes of nucleic acid molecules corresponding to the chromosome;
• determining a ranking of the chromosomes based on the statistical value;
• comparing the determined ranking of a first chromosome to another ranking of the first chromosome obtained from a reference biological sample;
• and
• based on the comparison, determining a classification of whether a fetal chromosomal aneuploidy exists for the first chromosome.

A computer program product comprising a non-transitory computer readable medium storing a plurality of instructions for controlling a processor to perform an operation for performing prenatal diagnosis of a fetal chromosomal aneuploidy in a biological sample obtained from a female subject pregnant with a fetus, wherein the biological sample includes nucleic acid molecules from the fetus and the female subject, the instructions comprising:

• for each of a plurality of the nucleic acid molecules in the biological sample:
• measuring a size of the nucleic acid molecule;
• identifying which chromosome the nucleic acid molecule is derived from;
• for each of a plurality of chromosomes, calculating a statistical value from the sizes of nucleic acid molecules corresponding to the chromosome;
• determining a ranking of the chromosomes based on the statistical value;
• comparing the determined ranking of a first chromosome to another ranking of the first chromosome obtained from a reference biological sample;
• and
• based on the comparison, determining a classification of whether a fetal chromosomal aneuploidy exists for the first chromosome.

A method for performing prenatal diagnosis of a fetal chromosomal aneuploidy in a biological sample obtained from a female subject pregnant with a fetus, wherein the biological sample includes nucleic acid molecules from the fetus and the female subject, the method comprising:

• for each of a plurality of the nucleic acid molecules in the biological sample:
• measuring a size of the nucleic acid molecule;
• identifying which chromosome the nucleic acid molecule is derived from;
• calculating, using a computer system, a first statistical value from the sizes of nucleic acid molecules corresponding to a first chromosome;
• calculating, using the computer system, a second statistical value from the sizes of nucleic acid molecules corresponding to one or more second chromosomes;
• determining a separation value between the first statistical value and the second statistical value;
• comparing the separation value to one or more cutoff values;
• and
• based on the comparison, determining a classification of whether a fetal chromosomal aneuploidy exists for the first chromosome.

A computer program product comprising a non-transitory computer readable medium storing a plurality of instructions for controlling a processor to perform an operation for performing prenatal diagnosis of a fetal chromosomal aneuploidy in a biological sample obtained from a female subject pregnant with a fetus, wherein the biological sample includes nucleic acid molecules from the fetus and the female subject, the instructions comprising:

• for each of a plurality of the nucleic acid molecules in the biological sample:
• measuring a size of the nucleic acid molecule;
• identifying which chromosome the nucleic acid molecule is derived from;
• calculating a first statistical value from the sizes of nucleic acid molecules corresponding to a first chromosome;
• calculating a second statistical value from the sizes of nucleic acid molecules corresponding to one or more second chromosomes;
• determining a separation value between the first statistical value and the second statistical value;
• comparing the separation value to one or more cutoff values;
• and
• based on the comparison, determining a classification of whether a fetal chromosomal aneuploidy exists for the first chromosome.