The application relates to methods and systems for proteomics and spatial mapping of biomolecules using a next generation sequencing readout to decipher biomolecular and cellular interaction networks. Specifically, disclosed are antenna networks generated by conjugating DNA antennas to proteins. The antennas carry a unique antenna identifier (UAI) sequence that can provide spatial location of the network, as well as biomolecules by transfer of the UAI to reporter oligonucleotides associated with other antennas and biomolecules. The methods and systems are also applicable to single cells.

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 and system for performing single molecule proteomics utilizing a nanopore sensor to measure an electronic signature of protein or peptide being transported through the nanopore from a first chamber to a second chamber. The protein's electronic signature is a function of ionic current over time. The method and system utilizing an agent, such as guanidinium chloride, to bind to the nanopore's interior and provide an electroosmotic force within the nanopore. The electroosmotic force, in some embodiments, enables stretching and unfolding of the protein during transport through the nanopore. The agent may also or alternatively induce the unfolding of the protein before transport through the nanopore and/or provide force moving the protein through the nanopore.

Methods and compositions for partitioning and analyzing cells are provided herein. The partitioning methods include encapsulating single cells in droplets, enabling biomolecule analysis at the single cell level. Further to this concept, multiple biomarkers can be quantified from single red blood cells, including methods which may determine whether a subject has undergone autologous blood transfer.

The invention relates to the field of genetically engineered nanopores and the use thereof in analyzing biopolymers and other (biological) compounds. Provided is a proteinaceous nanopore comprising a mutant pore-forming toxin, or a pore-forming fragment thereof, wherein the lumen-facing recognition region of the pore-forming protein or fragment thereof comprises one or more substitution(s) of lumen-facing amino acid(s) in the recognition region corresponding to amino acids 10-20 of Fragaceatoxin C (FraC), to a natural or non-natural aromatic amino acid residue.

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

Methods of identifying a crosslinking site or a binding site on a protein are described herein. The protein may comprise a binding site in a vicinity of the crosslinking site and identification of the crosslinking site may aid in identifying a location of the binding site in the protein. Methods of identifying a peptide or protein from a complex mixture are also described herein. The invention features a crosslinking agent that is configured to interact with a binding site of a protein and comprises a substituent configured to fragment in tandem mass spectrometry to yield a signature mass fragment.

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.

In a mass spectrum of fragment ions obtained by dissociating peptide-derived ions using the technique of irradiating the ions with hydrogen radicals, either pairs of a-type and c-type ions or those of z-type and z-type ions are characteristically observed. Since the mass difference of those ion pairs is previously known, a pair peak searcher 92 searches for pair peaks having a predetermined mass difference in a mass spectrum created by a mass spectrum creator 91, and adds to the detected pair peaks a piece of information indicating that they are pairs of a-type and c-type ions or those of x-type and z-type ions. When estimating the amino acid sequence of the peptide by a database search, a protein identifier 93 uses the ion-pair information in addition to the m/z value of each peak, whereby the accuracy of the estimation or identification the amino acid sequence can be improved.

The present invention is a method for measuring the amount of at least one molecule in a biological sample, the method comprising a) combining the sample, or a derivative thereof, with one or more aptamers and allowing one or more molecules in the sample to bind to the aptamer(s); b) separating bound from unbound molecules; and c) quantifying the molecule(s) bound to the or each aptamer, wherein quantification of the bound molecule(s) is carried out by sequencing at least part of the or each aptamer. Uses of and products derived from the method are also contemplated.