Abstract: Provided herein are methods of determining that a subject has or is at risk of having a disease (e.g., cancer) using analysis of gene expression of loci identified in nucleic acid molecules derived from a cell-free biological sample of the subject.

Abstract: A connection structure of a semiconductor device is provided in the present invention. The connection structure includes an interlayer dielectric, a top metal structure, and a passivation layer. The interlayer dielectric is disposed on a substrate. The top metal structure is disposed on the interlayer dielectric. The top metal structure includes a bottom portion and a top portion disposed on the bottom portion. The bottom portion includes a first sidewall, and the top portion includes a second sidewall. A slope of the first sidewall is larger than a slope of the second sidewall. The passivation layer is conformally disposed on the second sidewall, the first sidewall, and a top surface of the interlayer dielectric.

Abstract: In some aspects, the present disclosure provides methods for enriching amplicons, or amplification products, comprising a concatemer of at least two or more copies of a target polynucleotide. In some embodiments, a method comprises sequencing the amplicons comprising at least two or more copies of a target polynucleotide. In some embodiments, the target polynucleotides comprise sequences resulting from chromosome rearrangement, including but not limited to point mutations, single nucleotide polymorphisms, insertions, deletions, and translocations including fusion genes. In some aspects, the present disclosure provides compositions and reaction mixtures useful in the described methods.

Abstract: Methods for multiplex amplification of a plurality of targets of distinct sequence from a complex mixture are disclosed. In one aspect targets are circularized using a single circularization probe that is complementary to two regions in the target that flank a region to be amplified. The targets may hybridize to the circularization probe so that 5? or 3? flaps are generated and methods for removing flaps and circularizing the resulting product are disclosed. In another aspect targets are hybridized to dU probes so that 5? and 3? flaps are generated. The flaps are cleaved using 5? or 3? flap endonucleases or 3? to 5? exonucleases. The target sequences are then ligated to common primers, the dU probes digested and the ligated targets amplified.

Abstract: In some aspects, the present disclosure provides methods for identifying sequence variants in a nucleic acid sample. In some embodiments, a method comprises identifying sequence differences between sequencing reads and a reference sequence, and calling a sequence difference that occurs in at least two different circular polynucleotides, such as two circular polynucleotides having different junctions, or two different sheared polynucleotides as the sequence variant. In some aspects, the present disclosure provides compositions and systems useful in the described method.

Abstract: Provided herein are methods and systems for nucleic acid processing or analysis comprising generating a mixture comprising a first plurality of nucleic acid molecules derived from a biological sample of a subject, and a second plurality of nucleic acid molecules comprising sequences having at least one predetermined size; subjecting said first plurality of nucleic acid molecules, or derivative thereof; and second plurality of nucleic acid molecules or derivative thereof, to sequencing to generate a plurality of sequence reads; and processing said plurality of sequence reads to identify (i) a first set of sequence reads corresponding to at least a subset of said first plurality of nucleic acid molecules, and (ii) a second set of sequence reads corresponding to at least a subset of said second plurality of nucleic acid molecules, which second set of sequence reads corresponds to said sequences having said at least one predetermined size; and using said second set of sequence reads to identify one or more nuclei

Abstract: In some aspects, the present disclosure provides methods for enriching amplicons, or amplification products, comprising a concatemer of at least two or more copies of a target polynucleotide. In some embodiments, a method comprises sequencing the amplicons comprising at least two or more copies of a target polynucleotide. In some embodiments, the target polynucleotides comprise sequences resulting from chromosome rearrangement, including but not limited to point mutations, single nucleotide polymorphisms, insertions, deletions, and translocations including fusion genes. In some aspects, the present disclosure provides compositions and reaction mixtures useful in the described methods.

Abstract: Provided herein are methods for processing a plurality of nucleic acid molecules derived from a cell-free biological sample, comprising bringing said plurality of nucleic acid molecules or derivatives thereof in contact with a plurality of binding agents, to provide a first subset of said plurality of nucleic acid molecules coupled to said plurality of binding agents and a second subset of said plurality of nucleic acid molecules; separating said first subset of said plurality of nucleic acid molecules coupled to said plurality of binding agents from said second subset of said plurality of nucleic acid molecules; circularizing a nucleic acid molecule derived from said first subset of said plurality of nucleic acid molecules to obtain a circularized nucleic acid molecule; and identifying said circularized nucleic acid molecule or derivative thereof.

Abstract: In some aspects, the present disclosure provides methods for identifying sequence variants, as well as methods of determining copy number of a genetic locus in a sample. Systems and kits for performing methods of the disclosure, as well as compositions produced by or useful in methods of the disclosure are also provided. In some embodiments, methods comprise extending 3? ends of polynucleotides by adding one or more pre-determined nucleotides. In some embodiments, methods comprise use of a strand-tagging sequence.

Abstract: Provided herein are methods of cell-free nucleic acid size analysis. For example, methods herein can comprise preparing a first single stranded DNA library from a plurality of cell-free nucleic acid molecules from a subject and preparing a second single stranded DNA library from a plurality of cell-free nucleic acid molecules from a control.

Abstract: In some aspects, the present disclosure provides methods for identifying sequence variants in a nucleic acid sample. In some embodiments, a method comprises identifying sequence differences between sequencing reads and a reference sequence, and calling a sequence difference that occurs in at least two different circular polynucleotides, such as two circular polynucleotides having different junctions, or two different sheared polynucleotides as the sequence variant. In some aspects, the present disclosure provides compositions and systems useful in the described method.

Abstract: Various embodiments of the present disclosure are directed towards an integrated chip (IC). The IC comprises a substrate. A resistor overlies the substrate. The resistor comprises a resistive structure overlying the substrate. The resistor also comprises a conductive contact overlying and electrically coupled to the resistive structure. A capping structure is disposed over the conductive contact, wherein the capping structure extends laterally over an upper surface of the conductive contact and vertically along a first sidewall of the conductive contact, such that a lower surface of the capping structure is disposed below a lower surface of the conductive contact.

Abstract: In some aspects, the present disclosure provides methods for enriching amplicons, or amplification products, comprising a concatemer of at least two or more copies of a target polynucleotide. In some embodiments, a method comprises sequencing the amplicons comprising at least two or more copies of a target polynucleotide. In some embodiments, the target polynucleotides comprise sequences resulting from chromosome rearrangement, including but not limited to point mutations, single nucleotide polymorphisms, insertions, deletions, and translocations including fusion genes. In some aspects, the present disclosure provides compositions and reaction mixtures useful in the described methods.

Abstract: Provided herein are methods of determining that a subject has or is at risk of having a disease (e.g., cancer) using analysis of fragment enrichment or depletion on nucleic acid molecules derived from a cell-free biological sample of the subject.

Abstract: In some aspects, the present disclosure provides methods for identifying sequence variants, as well as methods of determining copy number of a genetic locus in a sample. Systems and kits for performing methods of the disclosure, as well as compositions produced by or useful in methods of the disclosure are also provided. In some embodiments, methods comprise extending 3? ends of polynucleotides by adding one or more pre-determined nucleotides. In some embodiments, methods comprise use of a strand-tagging sequence.

Abstract: In some aspects, the present disclosure provides methods for identifying sequence variants, as well as methods of determining copy number of a genetic locus in a sample. Systems and kits for performing methods of the disclosure, as well as compositions produced by or useful in methods of the disclosure are also provided.

Abstract: Provided herein are methods of determining that a subject has or is at risk of having a disease (e.g., cancer) using nucleic acid molecules derived from a cell-free biological sample of the subject.

Abstract: In some aspects, the present disclosure provides methods for enriching amplicons, or amplification products, comprising a concatemer of at least two or more copies of a target polynucleotide. In some embodiments, a method comprises sequencing the amplicons comprising at least two or more copies of a target polynucleotide. In some embodiments, the target polynucleotides comprise sequences resulting from chromosome rearrangement, including but not limited to point mutations, single nucleotide polymorphisms, insertions, deletions, and translocations including fusion genes. In some aspects, the present disclosure provides compositions and reaction mixtures useful in the described methods.

Abstract: Provided herein are methods and systems for detecting non-metastatic cancer in a subject, comprising measuring a total cfDNA fragment size distribution for the plurality of cfDNA nucleic acid molecules of the subject and comparing the total cfDNA fragment size distribution for the plurality of cfDNA nucleic acid molecules of the subject to the total cfDNA fragment size distribution for the plurality of cfDNA nucleic acid molecules from a healthy control.