The invention is directed to articles of manufacture for constraining movement of molecules, such as polynucleotides, and methods of using the same. In some embodiments, article of manufacture of the invention comprise (i) a solid state membrane having at least one aperture extending therethrough from a first side to a second side; (ii) an annular DNA sheet having a central opening disposed on the first side of the solid state membrane such that the annular DNA sheet spans an aperture and the central opening is aligned with the aperture to provide fluid communication between the first side and the second side of the solid state membrane through the aperture; and (iii) a protein nanopore immobilized in the central opening of the annular DNA sheet spanning the aperture. Uses of such articles of manufacture include determining sequences of nucleic acids.

Provided herein are high-throughput sequencing methods to study the diversity and functionality of lymphocyte receptor chains and pairing of the same. Specifically, the methods provided herein are used to identify with confidence one or more lymphocyte receptor chain pairs in a sample, for example one or more functional chain pairs.

Provided herein are high-throughput sequencing methods to study the diversity and functionality of lymphocyte receptor chains and pairing of the same. Specifically, the methods provided herein are used to identify with confidence one or more lymphocyte receptor chain pairs in a sample, for example one or more functional chain pairs.

Methods and compositions are provided for performing a set of N DNA sequencing reaction cycles whereby sequence information is obtained for approximately 2*N nucleotide bases.

The invention is directed to a method of sequencing low-complexity amplicons randomly arrayed at high density on a surface. Methods of the invention include preparing amplicons for sequencing by a sets of primers that ensure initial signals front different amplicons on the surface will be evenly distributed among the different nucleotides being added in a sequencing by synthesis operation.

The invention is directed to a method of sequencing low-complexity amplicons randomly arrayed at high density on a surface. Methods of the invention include preparing amplicons for sequencing by a sets of primers that ensure initial signals front different amplicons on the surface will be evenly distributed among the different nucleotides being added in a sequencing by synthesis operation.

A reaction mixture including (a) a nucleic acid having a primer hybridized to a template, (b) nucleotide analogs, wherein the nucleotide analogs have a blocking moiety; (c) a polymerase that is capable of forming an extended primer by adding the nucleotide analogs to the primer, and (d) a deblocking agent that is capable of removing the blocking moiety from the extended primer. Also provided is a method of synthesizing a polynucleotide including sequentially adding a plurality of the different nucleotides analogs to the nucleic acid via several reaction cycles in the reaction mixture, wherein each reaction cycle includes (i) the polymerase adding a nucleotide analog to the nucleic acid to form a transient nucleic acid species comprising a blocking moiety, and (ii) the deblocking agent modifying the transient nucleic acid species to remove the blocking moiety.

An ultra-fast solution to the problem of comparing genomes across sequencing technologies and genome freezes, while preserving privacy, is presented. A method for transforming a standard genome representation (i.e., a list of variants relative to a reference) into a fingerprint of the genome does not require knowledge of the technology, reference and encoding used, and yields fingerprints that can be readily compared to ascertain relatedness between two genome representations. Because of their reduced size, computation on the genome fingerprints is fast and requires little memory. This enables scaling up a variety of important genome analyses, including determinations of degree of relatedness, recognizing duplicative sequenced genomes in a set, and many others. Because the original genome representation cannot be reconstructed from its fingerprint, the method also has significant implications for privacy-preserving genome analytics.

A sample processing system includes a sample carrier support configured to concurrently support multiple sample carriers in series, each sample carries carrying a respective sample to be processed. The apparatus also includes a plurality of processing stations located at different positions along the sample carry support, each processing station configured to perform a different processing act of a plurality of processing acts to be performed on each sample. The apparatus further includes a support mover that moves the sample support and hence the sample carriers sequentially from processing station to processing station for processing.

A bioinformatics process which provides an improved means to detect a JAK-STAT3 cellular signaling pathway in a subject, such as a human, based on the expression levels of at least three unique target genes of the JAK-STAT3 cellular signaling pathway measured in a sample. The invention includes an apparatus comprising a digital processor configured to perform such a method, a non-transitory storage medium storing instructions that are executable by a digital processing device to perform such a method, and a computer program comprising program code means for causing a digital processing device to perform such a method. Kits are also provided for measuring expression levels of unique sets of JAK-STAT3 cellular signaling pathway target genes.