A gene sequencing reaction device, a gene sequencing system and a gene sequencing reaction method. The gene sequencing reaction device includes: a supporting platform; a dipping container disposed on the supporting platform, wherein the dipping container has a dipping reaction area, and the dipping reaction area is configured to hold a chemical reagent for gene sequencing reaction, so as to dip a sequencing chip having a DNA sample loading structure on the surface and having a DNA sample loaded thereon in the chemical reagent to perform a gene sequencing reaction; a temperature control apparatus, configured to control the temperature of the chemical reagent in the dipping reaction area; and a transfer apparatus, configured to insert the sequencing chip into the dipping reaction area or pull out the sequencing chip from the dipping reaction area.

The present disclosure provides methods for determining the ploidy status of a chromosome in a gestating fetus from genotypic data measured from a mixed sample of DNA comprising DNA from both the mother of the fetus and from the fetus, and optionally from genotypic data from the mother and father. The ploidy state is determined by using a joint distribution model to create a plurality of expected allele distributions for different possible fetal ploidy states given the parental genotypic data, and comparing the expected allelic distributions to the pattern of measured allelic distributions measured in the mixed sample, and choosing the ploidy state whose expected allelic distribution pattern most closely matches the observed allelic distribution pattern. The mixed sample of DNA may be preferentially enriched at a plurality of polymorphic loci in a way that minimizes the allelic bias, for example using massively multiplexed targeted PCR.

Disclosed are particles which are introduced into target cells and suppress the expression of specific genes, and a method of manufacturing such particles. More particularly, the present invention relates to DNA-RNA hybrid particles that comprise a DNA strand and an RNA strand that binds to the DNA strand through partial complementary base pairing, in which the DNA strand comprises an aptamer sequence that is able to bind to a target protein produced in a target cell, and the RNA strand comprises an siRNA sequence that binds to a target RNA in the target cell to suppress protein expression from the target RNA. Such hybrid particles are capable of effectively delivering an siRNA therapeutic agent into target cells for the treatment of disease, and have resistance against digestion by in vivo nucleases, DNase and RNase, owing to complementary binding formed between DNA and RNA strands. Also, the present invention relates to a method of manufacturing such DNA-RNA hybrid particles.

Disclosed are particles which are introduced into target cells and suppress the expression of specific genes, and a method of manufacturing such particles. More particularly, the present invention relates to DNA-RNA hybrid particles that comprise a DNA strand and an RNA strand that binds to the DNA strand through partial complementary base pairing, in which the DNA strand comprises an aptamer sequence that is able to bind to a target protein produced in a target cell, and the RNA strand comprises an siRNA sequence that binds to a target RNA in the target cell to suppress protein expression from the target RNA. Such hybrid particles are capable of effectively delivering an siRNA therapeutic agent into target cells for the treatment of disease, and have resistance against digestion by in vivo nucleases, DNase and RNase, owing to complementary binding formed between DNA and RNA strands. Also, the present invention relates to a method of manufacturing such DNA-RNA hybrid particles.

A nucleic acid amplification reaction method includes subjecting a reaction mixture containing a nucleic acid amplification reaction reagent to be used for amplifying a nucleic acid to a thermal cycle for amplifying the nucleic acid, wherein in the thermal cycle, a heating time for an annealing reaction and an elongation reaction is 1 sec or more and 10 sec or less, the nucleic acid amplification reaction reagent contains a forward primer, a reverse primer, a polymerase, and a fluorescently labeled probe, the concentration of the forward primer is 0.4 μM or more and 3.2 μM or less, the concentration of the reverse primer is 0.4 μM or more and 3.2 μM or less, the amount of the polymerase is 0.5 U or more and 4 U or less, and the concentration of the fluorescently labeled probe is 0.15 μM or more and 1.2 μM or less.

A nucleic acid amplification reaction method includes subjecting a reaction mixture containing a nucleic acid amplification reaction reagent to be used for amplifying a nucleic acid to a thermal cycle for amplifying the nucleic acid, wherein in the thermal cycle, a heating time for an annealing reaction and an elongation reaction is 1 sec or more and 10 sec or less, the nucleic acid amplification reaction reagent contains a forward primer, a reverse primer, a polymerase, and a fluorescently labeled probe, the concentration of the forward primer is 0.4 μM or more and 3.2 μM or less, the concentration of the reverse primer is 0.4 μM or more and 3.2 μM or less, the amount of the polymerase is 0.5 U or more and 4 U or less, and the concentration of the fluorescently labeled probe is 0.15 μM or more and 1.2 μM or less.

The present invention provides methods, systems, kits, and compositions for magnetically purifying target nucleic acid sequences from a sample using bait molecules configured to bind both target nucleic acid sequences and magnetic binding particles. In certain embodiments, the bait molecules comprise a short target capture sequence (e.g., 18 to 48 bases), and the methods employ a short hybridization time (e.g., 1-4 hours) and a low hybridization temperature (e.g., about room temperature).

The present invention provides methods, systems, kits, and compositions for magnetically purifying target nucleic acid sequences from a sample using bait molecules configured to bind both target nucleic acid sequences and magnetic binding particles. In certain embodiments, the bait molecules comprise a short target capture sequence (e.g., 18 to 48 bases), and the methods employ a short hybridization time (e.g., 1-4 hours) and a low hybridization temperature (e.g., about room temperature).

This disclosure provides, among other things, methods for generating and applying therapeutic interventions. The methods involve, for example, (a) sequencing polynucleotides from cancer cells from a subject; (b) identifying and quantifying somatic mutations in the polynucleotides; (c) developing a profile of tumor heterogeneity in the subject indicating the presence and relative quantity of a plurality of the somatic mutations in the polynucleotides, wherein different relative quantities indicates tumor heterogeneity; and (d) determining a therapeutic intervention for a cancer exhibiting the tumor heterogeneity, wherein the therapeutic intervention is effective against a cancer having the profile of tumor heterogeneity determined.

This disclosure provides, among other things, methods for generating and applying therapeutic interventions. The methods involve, for example, (a) sequencing polynucleotides from cancer cells from a subject; (b) identifying and quantifying somatic mutations in the polynucleotides; (c) developing a profile of tumor heterogeneity in the subject indicating the presence and relative quantity of a plurality of the somatic mutations in the polynucleotides, wherein different relative quantities indicates tumor heterogeneity; and (d) determining a therapeutic intervention for a cancer exhibiting the tumor heterogeneity, wherein the therapeutic intervention is effective against a cancer having the profile of tumor heterogeneity determined.