Methods, apparatus, and processes which use Extreme ultraviolet radiation (EUV) and/or soft X-ray wavelengths to read, image, edit, locate, identify, map, alter, delete, repair and sequence genes are described. An EUV scanning tool which allows high throughput genomic scanning of DNA, RNA and protein sequences is also described. A database which records characteristic absorption spectra of gene sequences is also described.

An object of the present invention is to provide a method for efficiently identifying a polyubiquitinated substrate which is generally not easily identified. The method for identifying a polyubiquitinated substrate includes (1) a step of expressing a trypsin-resistant polyubiquitin chain-binding protein and a ubiquitin ligase in a cell, (2) a step of isolating a complex that contains the trypsin-resistant polyubiquitin chain-binding protein from the cell having undergone the step (1), (3) a step of subjecting the complex isolated by the step (2) to trypsin digestion, and (4) a step of identifying a peptide that has a ubiquitination site from a digested material obtained by the step (3).

Identifying proteins and peptides, and more specifically large-scale sequencing of single peptides in a mixture of diverse peptides at the single molecule level is an unmet challenge in the field of protein sequencing. Herein are methods for identifying amino acids in peptides, including peptides with one or more unnatural amino acids. In one embodiment, the N-terminal amino acid is labeled with a first label and an internal amino acid is labeled with a second label. In some embodiments, the labels are fluorescent labels. In other embodiments, the internal amino acid is Lysine. In other embodiments, amino acids in peptides are identified based on the fluorescent signature for each peptide at the single molecule level.

Described herein are immune binding proteins and method for obtaining immune binding proteins from genomic or other sources. Also described herein are nucleic acids encoding the immune binding proteins in which the natural multimeric association of chains is maintained in the nucleic acids and the immune binding proteins made therefrom. For example, nucleic acids encoding antibodies that are amplified from a B-cell using the methods described herein maintain the natural pairing of heavy and light chains from the B-cell. This maintenance of pairing (or multimerization) produces libraries and/or repertoires of immune binding proteins that are enriched for useful binding molecules.

Methods and apparatuses relating to large scale FET arrays for analyte detection and measurement are provided. ChemFET (e.g., ISFET) arrays may be fabricated using conventional CMOS processing techniques based on improved FET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense arrays. Improved array control techniques provide for rapid data acquisition from large and dense arrays. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in a wide variety of chemical and/or biological processes.

Methods of sequencing a protein using a novel digestion-on-emitter technology are provided.

The present disclosure provides a rapid, scalable, and high-throughput method of identifying the precise regions in a receptor protein which are involved in binding of a molecule of interest. The method of the instant disclosure is useful where the crystal structure of a protein of interest is not available. Also provided are surface display libraries, and methods of making the same.

Methods for nanopore-based protein analysis are provided. The methods address the characterization of a target protein analyte, which has a dimension greater than an internal diameter of the nanopore tunnel, and which is also physically associated with a polymer. The methods further comprise applying an electrical potential to the nanopore system to cause the polymer to interact with the nanopore tunnel. The ion current through the nanopore is measured to provide a current pattern reflective of the structure of the portion of the polymer interacting with the nanopore tunnel. This is used as a metric for characterizing the associated protein that does not pass through the nanopore.

The invention provides methods, compositions, and kits for the characterisation and analysis of proteins. Methods are provided for determining, on a protein, a binding site for a binding partner, the methods comprising: contacting a protein with a plurality of monomers, and polymerising the monomers to create a protein:polymer complex; digesting the protein in the complex to produce a peptide:polymer complex; isolating the peptide:polymer complex; and sequencing the peptide, wherein the peptide corresponds to a binding site for a binding partner.

Identifying proteins and peptides, and more specifically large-scale sequencing of single peptides in a mixture of diverse peptides at the single molecule level is an unmet challenge in the field of protein sequencing. Herein are methods for identifying amino acids in peptides, including peptides comprising unnatural amino acids. In one embodiment, the N-terminal amino acid is labeled with a first label and an internal amino acid is labeled with a second label. In some embodiments, the labels are fluorescent labels. In other embodiments, the internal amino acid is Lysine. In other embodiments, amino acids in peptides are identified based on the fluorescent signature for each peptide at the single molecule level.