The present invention includes composition and methods for making and using a combinatorial library to identify modified thioaptamers that bind to, and affect the immune response of a host animal, transcription factors such as IL-6, NF-B, AP-1 and the like. Composition and methods are also provided for the treatment of viral infections, as well as, vaccines and vaccine adjuvants are provided that modify host immune responses.

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.

A method of generating an inclusion list for targeted mass spectrometric analysis is disclosed. Experimentally-acquired data for a plurality of isobarically-labeled peptides derived by proteolytic digestion of a corresponding protein. The data includes, for each of the isobarically-labeled peptides, a mass-to-charge (m/z) ratio, a charge state, and a chromatographic retention time (RT). The method includes determining a hydrophobicity index (HI) of an unlabeled peptide corresponding to the isobarically-labeled peptide. If the determined HI is less than a threshold value, a substitute unlabeled peptide is selected in accordance with predetermined criteria and predicted properties for the substitute peptide are determined and stored on an inclusion list. If the determined HI for the unlabeled peptide is at least as great as the threshold value, predicted properties for the unlabeled peptide are determined and stored on an inclusion list. The substitute unlabeled peptide may be selected from an available peptide library.

Disclosed are nanofluidic analytical devices. The devices employ a sample processing region that includes a plurality of fluidically connected sample handling elements that, in combination, affect a physical change on a sample introduced into the sample processing region. This physical change can include, for example, purification of an analyte of interest present in the sample, concentration of an analyte of interest present in the sample, chemical modification (e.g., cleavage and/or chemical derivatization) of an analyte of interest present in the sample, or a combination thereof. The analytical devices further include a nanochannel comprising a plurality of in-plane nanopores in series fluidically coupled to the sample processing region. The in-plane nanopores can be used to detect and/or analyze analyte(s) present in the sample following processing by the sample processing region. These analytical devices can advantageously provide for the label-free detection of single molecules.

The disclosure provides methods and compositions that enable the identification of polypeptides having one or more post-translational modifications. In some embodiments, the disclosure provides a method (e.g., a single-molecule measurement method) comprising contacting a single polypeptide with one or more post-translational modification-specific (PTM-specific) affinity reagents; and identifying whether the single polypeptide comprises a post-translational modification (PTM) by determining a luminescence signature representative of the binding interaction(s) between the single polypeptide and the one or more PTM-specific affinity reagents.

Novel approaches for processing polymeric analytes, such as biopolymers, are provided herein. A method for processing a polymeric analyte may comprise coupling a monomer of the polymeric analyte to a capture moiety, cleaving the monomer from the polymeric analyte, and analyzing the cleaved monomer, e.g., using a binding agent. The methods described herein may employ the use of activating agents.

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

Provided herein are methods of characterising a target polypeptide as it moves with respect to a nanopore. Also provided are related kits, systems and apparatuses for carrying out such methods.

Provided herein are methods and systems for sequencing proteins. One or more methods disclosed herein may use linkers comprising an amino acid-reactive group and an additional reactive moiety that may be used to couple a polymerizable molecule. The linker may couple to a polymerizable molecule and an amino acid of a peptide and a capture moiety via the polymerizable molecule, followed by cleavage of the amino acid from the peptide. Further processing and analysis may be conducted using, for example, nanopores or nanogaps.