Provided is a device including: at least one well in which an amplifiable reagent is contained in a specific copy number of less than 100; and at least one well in which the amplifiable reagent is contained in a specific copy number of 100 or greater, wherein for the at least one well in which the specific copy number of the amplifiable reagent is less than 100, a formula: CV<1/√x is established, where CV represents a coefficient of variation for the specific copy number and x represents average specific copy number of the amplifiable reagent.

Disclosed herein include systems and methods for designing probes for depleting abundant transcripts from a sample. Abundant sequence reads can be determined in a species-agnostic manner, and probes for depleting abundant transcripts can be designed based on the sequences of the top abundant sequences. Also disclosed herein include compositions and kits for depleting abundant transcripts and methods for depleting abundant transcripts.

Disclosed herein include systems and methods for designing probes for depleting abundant transcripts from a sample. Abundant sequence reads can be determined in a species-agnostic manner, and probes for depleting abundant transcripts can be designed based on the sequences of the top abundant sequences. Also disclosed herein include compositions and kits for depleting abundant transcripts and methods for depleting abundant transcripts.

Disclosed are methods and systems for enumeration of nucleic acids, including for the detection of rare events in a biological sample. In certain embodiments, the method may comprise arranging polynucleotides obtained from a biological sample to form a plurality of reaction sites, wherein each reaction site contains on average one polynucleotide; amplifying the polynucleotides in the plurality of reaction sites; determining by nucleic acid hybridization (i) a first number of first reaction sites containing a target nucleic acid sequence, or a portion thereof, and (ii) a second number of second reaction sites containing a reference nucleic acid sequence, or a portion thereof; comparing the first number of the first reaction sites to the second number of the second reaction sites to determine the relative amount of the target nucleic acid in the biological sample.

Disclosed are methods and systems for enumeration of nucleic acids, including for the detection of rare events in a biological sample. In certain embodiments, the method may comprise arranging polynucleotides obtained from a biological sample to form a plurality of reaction sites, wherein each reaction site contains on average one polynucleotide; amplifying the polynucleotides in the plurality of reaction sites; determining by nucleic acid hybridization (i) a first number of first reaction sites containing a target nucleic acid sequence, or a portion thereof, and (ii) a second number of second reaction sites containing a reference nucleic acid sequence, or a portion thereof; comparing the first number of the first reaction sites to the second number of the second reaction sites to determine the relative amount of the target nucleic acid in the biological sample.

A classification of a level of cancer in an organism is determined by analyzing a biological sample of the organism. The biological sample comprises clinically-relevant DNA and other DNA. At least some of the DNA is cell-free in the biological sample. An amount of a first set of DNA fragments from the biological sample corresponding to each of a plurality of sizes is measured. A first value of a first parameter is calculated based on the amounts of DNA fragments at the plurality of sizes. The first value is compared to a reference value. A classification of a level of cancer in the organism is determined based on the comparison.

A classification of a level of cancer in an organism is determined by analyzing a biological sample of the organism. The biological sample comprises clinically-relevant DNA and other DNA. At least some of the DNA is cell-free in the biological sample. An amount of a first set of DNA fragments from the biological sample corresponding to each of a plurality of sizes is measured. A first value of a first parameter is calculated based on the amounts of DNA fragments at the plurality of sizes. The first value is compared to a reference value. A classification of a level of cancer in the organism is determined based on the comparison.

Disclosed are methods for determining at least one sequence of interest of a fetus of a pregnant mother. In various embodiments, the method can determine one or more sequences of interest in a test sample that comprises a mixture of maternal cellular DNA and mother-and-fetus cfDNA. In some embodiments, methods are provided for determining whether the fetus has a genetic disease. In some embodiments, methods are provided for determining whether the fetus is homozygous in a disease causing allele when the mother is heterozygous of the same allele. In some embodiments, methods are provided for determining whether the fetus has a copy number variation (CNV) or a non-CNV genetic sequence anomaly.

Disclosed are methods for determining at least one sequence of interest of a fetus of a pregnant mother. In various embodiments, the method can determine one or more sequences of interest in a test sample that comprises a mixture of maternal cellular DNA and mother-and-fetus cfDNA. In some embodiments, methods are provided for determining whether the fetus has a genetic disease. In some embodiments, methods are provided for determining whether the fetus is homozygous in a disease causing allele when the mother is heterozygous of the same allele. In some embodiments, methods are provided for determining whether the fetus has a copy number variation (CNV) or a non-CNV genetic sequence anomaly.

The present invention relates to a method for reducing a noise level of a data set for a target analyte in a sample. The present invention can reduce a noise level of a data set to a proper level conveniently by applying a noise-reduction ratio to the data set thereby the possibility of false positive may be reduced effectively. According to the present invention, the calibrated data set is obtained by using the noise-reduction ratio, so that the noise level of a data set is reduced without change of signal ratio between the data point in the data set.