The present disclosure provides methods for molecular neighborhood detection of molecules, such as by iterative proximity ligation or split-and-pool methods for obtaining positional information.

The present invention provides methods and systems for identifying and classifying patterns comprising the T cell exposed motifs and the frequencies of such motifs in collections of proteins that make up the human proteome, immunoglobulinome, T cell receptor repertoire or microbiome, and other proteomes of environmental of microbial origin, or subsets thereof. It further provides graphical representations that facilitate comparisons of T cell exposed motif patterns between samples or between time points. The present invention also provides methods and systems for identifying and classifying patterns in repertoires of cells including receptor bearing cells and cells of tissue samples and detecting patterns of utility in diagnosis and monitoring of health and disease.

The present disclosure based on the inventors' recognition that PAN domain containing proteins play important immune regulating functions. Disclosed herein are methods for modulating immune responses in plants and animals, improving in vitro fertilization efficiency, and inhibiting human cell division and cellular migration in cancer cells. Also disclosed herein are genetically modified plants that are resistant to pathogenic infections.

The present disclosure provides methods and compositions for protein quantification using peptide barcodes, sample preparation for protein quantification, protein quantification using error-resistant peptide barcodes, methods to manipulate barcoded proteins, methods to determine the binding affinities of many protein variants in a mixture of proteins by single molecule measurements.

A method for processing a biomolecule may comprise providing, at a first location, (i) a substrate and (ii) a substrate holder coupled to the substrate. The substrate may comprise the biomolecule coupled thereto. The substrate holder and the substrate may be automatically directed from the first location to a second location different from the first location. At the second location, the biomolecule may be processed to provide a processed biomolecule coupled to the substrate. The processing may comprise labelling the biomolecule to provide a labeled biomolecule.

Disclosed herein are methods and compositions for purifying proteins from crude solutions.

Embodiments disclosed herein are directed to recognition tunneling systems, methods and devices, and more particularly, to chemical reactions for selectively labeling proteins and peptides and placing protein and/or peptides into, or onto a nanopore formed in a solid support and threading such in and/or through the nanopore, with such nanopores, in some embodiments, including a molecular motor to pull or otherwise force the protein/peptide through the nanopore.

Disclosed herein are methods and compositions for purifying proteins from crude solutions.

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.

Described are antagonistic TNFR2 polypeptides, such as antibodies and antigen-binding fragments thereof, and the use of these polypeptides to inhibit the proliferation of regulatory T cells (T-regs) and/or myeloid-derived suppressor cells (MDSCs), to expand T effector cell populations or function, and to reduce the proliferation of, or directly kill, tumor cells, such as tumor cells that express TNFR2 antigen. The polypeptides, such as antibodies and antigen-binding fragments thereof, are TNFR2 antagonists, such as dominant TNFR2 antagonists. The polypeptides can be used to suppress the T-reg- or MDSC-mediated deactivation of tumor reactive T lymphocytes, expand populations of tumor-reactive cytotoxic T cells, and/or to directly kill TNFR2+ tumor cells. The antagonistic TNFR2 polypeptides described herein can be used to treat a wide variety of cancers and infectious diseases.