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.

The present document describes nucleic acid structures comprising a plurality of annealed motifs that are made from complementary oligonucleotides having domains with sequences complementary to other nucleotides of the motif. The annealed motifs may be anchored to surfaces, and functional elements may be attached to the annealed motifs. The nucleic acid structures may used to make sensors therefrom. The present document also describes methods to generate said nucleic acid structures.

The present document describes nucleic acid structures comprising a plurality of annealed motifs that are made from complementary oligonucleotides having domains with sequences complementary to other nucleotides of the motif. The annealed motifs may be anchored to surfaces, and functional elements may be attached to the annealed motifs. The nucleic acid structures may used to make sensors therefrom. The present document also describes methods to generate said nucleic acid structures.

The invention encompasses novel methods of operating electrochemical sensors such as aptamer-based sensors to analyze complex samples, such as flowing whole blood both in vitro or in vivo. In such environments, electrochemical sensors are often subject to drift, which complicates the interpretation of sensor output in terms of target concentration. The method of the invention utilizes a dual-reporter recognition element that generates a first, sensing current that is responsive to target binding and to environmental factors and a second, reference current that is only affected by environmental factors. The reference current provides information about environmentally-induced drift, which allows the drift effect to be subtracted out. By removing drift artifacts, electrochemical sensors may be deployed to analyze complex samples, such as whole blood, in vivo.

The invention encompasses novel methods of operating electrochemical sensors such as aptamer-based sensors to analyze complex samples, such as flowing whole blood both in vitro or in vivo. In such environments, electrochemical sensors are often subject to drift, which complicates the interpretation of sensor output in terms of target concentration. The method of the invention utilizes a dual-reporter recognition element that generates a first, sensing current that is responsive to target binding and to environmental factors and a second, reference current that is only affected by environmental factors. The reference current provides information about environmentally-induced drift, which allows the drift effect to be subtracted out. By removing drift artifacts, electrochemical sensors may be deployed to analyze complex samples, such as whole blood, in vivo.

The present invention provides an improved immuno-PCR method by using cDNA display comprising the steps of: immobilizing a first antibody having a binding site to a solid phase: contacting a sample fluid to said antibody to bind a target molecule in said sample fluid; contacting said target molecule to a cDNA display being composed of a backbone being composed of a double strand and a side chain having a second antigen binding site to which the second antibody is bound; and conducting polymerase chain reaction to detect said cDNA quantitatively. According to the improved immune-PCR method of the present invention, the target molecule is screened and obtained quantitatively, because it uses cDNA display being composed of one protein/peptide and one DNA.

The present invention provides an improved immuno-PCR method by using cDNA display comprising the steps of: immobilizing a first antibody having a binding site to a solid phase: contacting a sample fluid to said antibody to bind a target molecule in said sample fluid; contacting said target molecule to a cDNA display being composed of a backbone being composed of a double strand and a side chain having a second antigen binding site to which the second antibody is bound; and conducting polymerase chain reaction to detect said cDNA quantitatively. According to the improved immune-PCR method of the present invention, the target molecule is screened and obtained quantitatively, because it uses cDNA display being composed of one protein/peptide and one DNA.

The present invention relates to a composition of primers for detecting HSIL comprising a first set of primers, called splice junctions set of primers which comprises at least 2 pairs of primers of each of a first subset of pairs of primers specific of HPV16, a second subset specific of HPV18, a third subset specific of HPV31, a fourth subset specific of HPV33, a fifth subset specific of HPV35, a sixth subset specific of HPV39, a seventh subset specific of HPV45, a eighth subset specific of HPV51, a ninth subset specific of HPV52, a tenth subset specific of HPV56, an eleventh subset specific of HPV58, a twelfth subset specific of HPV59 and a thirteenth subset specific of HPV66.

The present invention relates to a composition of primers for detecting HSIL comprising a first set of primers, called splice junctions set of primers which comprises at least 2 pairs of primers of each of a first subset of pairs of primers specific of HPV16, a second subset specific of HPV18, a third subset specific of HPV31, a fourth subset specific of HPV33, a fifth subset specific of HPV35, a sixth subset specific of HPV39, a seventh subset specific of HPV45, a eighth subset specific of HPV51, a ninth subset specific of HPV52, a tenth subset specific of HPV56, an eleventh subset specific of HPV58, a twelfth subset specific of HPV59 and a thirteenth subset specific of HPV66.

Disclosed herein include systems, methods, compositions, and kits for PCR normalization. In some embodiments, after barcoding copies of a higher abundance target (e.g., a cDNA species), the barcoded copies are amplified using a pair of forward primers comprising one or more mismatches and a reverse primer. The amplified copies can be further linearly amplified using a forward primer comprising the sequence of one of the pair of forward primers, and a reverse primer.