Various approaches for generating read-sets from nucleic acid molecules and segments and phasing are disclosed. Nucleic acids are assembled into complexes using binding moieties and exposed nucleic acid ends are tagged with nucleic acid tags. Read-sets can be generated from tagged nucleic acid molecules and segments. Physical linkage relationships between nucleic acid molecules and segments can be examined using the nucleic acid tags. Various approaches to generating read-sets and phasing are presented.

The present disclosure relates to novel macrocyclic compounds and libraries thereof that are useful as research tools for drug discovery efforts. This disclosure also relates to methods of preparing these compounds and libraries and methods of using these libraries, such as in high throughput screening. In particular, these libraries are useful for evaluation of bioactivity at existing and newly identified pharmacologically relevant targets, including G protein-coupled receptors, nuclear receptors, enzymes, ion channels, transporters, transcription factors, protein-protein interactions and nucleic acid-protein interactions. As such, these libraries can be applied to the search for new pharmaceutical agents for the treatment and prevention of a range of medical conditions.

Aluminum coated glass slides provide a novel glycan array platform. Specifically, aluminum coated glass slides increase sensitivity of fluorescent based assay methods. Additionally, aluminum coated glass slides allows for mass spectroscopic analysis of carbohydrates and provide a platform for examining activity of cellulases. The unique properties of ACG slides include: 1) the metal oxide layer on the surface can be activated for grafting organic compounds such as modified oligosaccharides; 2) the surface remains electrically conductive, and the grafted oligosaccharides can be simultaneously characterized by mass spectrometry and carbohydrate-binding assay; and 3) the slides are more sensitive than transparent glass slides in binding analysis.

Provided herein are devices for the manufacturing of high-quality oligonucleic acids. Longer nucleic acids, e.g., genes, can be synthesized in parallel using microfluidic assemblies described herein. Devices described herein include silicon plates having a plurality of channels in fluid communication with a plurality of microchannels. The number of microchannels and dimensions of the microchannels provide for rapid exchange of chemical exposure during de novo synthesis of oligonucleic acids.

The present disclosure provides methods, compositions, kits, and systems useful in the determination and evaluation of the immune repertoire using genomic DNA from a biological sample. In one aspect, target-specific primer panels provide for the effective amplification of sequences of T cell receptor and/or B cell receptor chains with improved sequencing accuracy and resolution over the repertoire. Nucleic acid sequences of variable regions associated with the immune cell receptor are determined to effectively portray clonal diversity of a biological sample and/or differences associated with the immune cell repertoire of a biological sample.

The present disclosure provides methods, compositions, kits, and systems useful in the determination and evaluation of the immune repertoire using genomic DNA from a biological sample. In one aspect, target-specific primer panels provide for the effective amplification of sequences of T cell receptor and/or B cell receptor chains with improved sequencing accuracy and resolution over the repertoire. Nucleic acid sequences of variable regions associated with the immune cell receptor are determined to effectively portray clonal diversity of a biological sample and/or differences associated with the immune cell repertoire of a biological sample.

Provided herein are methods and systems for detecting tissue conditions. In some aspects, levels of at least one marker of a disease or condition and at least one tissue-specific cell-free polynucleotide are quantified, levels are compared to a reference, and it is determined whether the tissue has been damaged by the disease or condition based on the comparing. Systems for performing the methods described herein are also provided.

Provided is a method for obtaining a double-stranded sequence by single-stranded rolling circle amplification, comprising: 1) performing rolling circle amplification reaction on single-stranded circular DNA by means of a first primer to obtain an amplified sequence, the first primer being complementary to a partial region of the single-stranded circular DNA, and the single-stranded circular DNA having a break mechanism that can cause the single-stranded circular DNA to ring-open; 2) ring-opening the single-stranded circular DNA by means of the break mechanism to obtain single-stranded linear DNA; and 3) using the single-stranded linear DNA as a second primer and using the amplified sequence obtained in step 1) as a template to perform amplification reaction to obtain an amplified double-stranded sequence.

Provided herein are polypeptides that bind to a transferrin receptor, methods of generating such polypeptides, and methods of using the polypeptides to target a composition to a transferrin receptor-expressing cell.

Provided herein are polypeptides that bind to a transferrin receptor, methods of generating such polypeptides, and methods of using the polypeptides to target a composition to a transferrin receptor-expressing cell.