Abstract: Described herein, among other things, is a method of sequencing, comprising: concatenating a plurality of fragments of genomic DNA to produce concatenated DNA; sequencing the concatenated DNA to produce a plurality of sequence reads, wherein at least some of the sequence reads comprise: at least the sequence of the 3? and/or 5? ends of a fragment that corresponds to the locus of interest and sequence of one or both of the fragments that flank the fragment in the concatenated DNA; and grouping the sequence reads that corresponds to the locus of interest using, for each of the grouped sequence reads: the 3? and/or 5? end sequences; and/or the flanking sequence.

Abstract: The invention relates to mutant forms of CsgG. The invention also relates to analyte detection and characterization using CsgG.

Abstract: The invention relates to mutant forms of lysenin. The invention also relates to analyte characterisation using the mutant forms of lysenin.

Abstract: The invention relates to a new method of characterising two or more target polynucleotides using a pore. The method involves sequentially attaching to a first polynucleotide one or more subsequent polynucleotides to form a concatenated polynucleotide.

Abstract: A target polynucleotide is expanded. In respect of each nucleotide in the target polynucleotide, the target polynucleotide comprises clock nucleotides and at least one signal nucleotide in a predetermined order. The clock nucleotides have a predetermined sequence common to each nucleotide in the target polynucleotide. The at least one signal nucleotide is characteristic of the identity of the respective nucleotide in the target polynucleotide. During translocation of the expanded polynucleotide through a nanopore, electrical measurements dependent on the polynucleotide within the pore are made, to derive an analysis signal. Clock signals derived from the clock nucleotides are identified. Relative to the positions of the identified clock signals, nucleotide signals derived from the least one signal nucleotide are derived to analyse the target polynucleotide.

Abstract: An array of membranes comprising amphipathic molecules is formed using an apparatus comprising a support defining an array of compartments. Volumes comprising polar medium are provided within respective compartments and a layer comprising apolar medium is provided extending across the openings with the volumes. Polar medium is flowed across the support to displace apolar medium and form a layer in contact with the volumes, forming membranes comprising amphipathic molecules at the interfaces. In one construction of the apparatus, the support that comprises partitions which comprise inner portions and outer portions. The inner portions define inner recesses without gaps therebetween that are capable of constraining the volumes comprising polar medium contained in neighbouring inner recesses from contacting each other. The outer portions extend outwardly from the inner portions and have gaps allowing the flow of an apolar medium across the substrate.

Abstract: The invention relates to constructs comprising a transmembrane protein pore subunit and a nucleic acid handling enzyme. The pore subunit is covalently attached to the enzyme such that both the subunit and enzyme retain their activity. The constructs can be used to generate transmembrane protein pores having a nucleic acid handling enzyme attached thereto. Such pores are particularly useful for sequencing nucleic acids. The enzyme handles the nucleic acid in such a way that the pore can detect its component nucleotides by stochastic sensing.

Abstract: The invention relates to a new method of determining the presence, absence or characteristics of an analyte. The analyte is coupled to a membrane. The invention also relates to nucleic acid sequencing.

Abstract: The invention relates to mutant forms of CsgG. The invention also related to analyte detection and characterisation using CsgG.

Abstract: The invention relates to a new method of characterizing a target polynucleotide. The method uses a pore and a Hel308 helicase or a molecular motor which is capable of binding to the target polynucleotide at an internal nucleotide. The helicase or molecular motor controls the movement of the target polynucleotide through the pore.

Abstract: The invention relates to a new method of characterising a target RNA polynucleotide by taking one or more measurements as the target RNA polynucleotide moves with respect to a transmembrane pore. The movement is controlled by a DNA helicase. The invention also relates to a modified RNA construct wherein the RNA polynucleotide has been modified to increase DNA helicase binding thereto.

Abstract: A kit which has a first and second component parts, which are adapted for connection with each other. The first component part has a first array of electrical sensors, two substantially parallel lateral walls on the sides of the electrical connectors, two rails extending along the sides of the array, a front contact point and an overhang for receiving the second part. The second component part has a second array of electrical sensors for connection to the first array, front end configured to fit between the lateral walls of the first connector, and lateral sides having rail reliefs to fit the rails of the first connector. Connection of the first component part and the second component part forms a shoulder that aligns to locate the second array of electrical connectors in correct position for connection to the first array of electrical connectors.

Abstract: The invention relates to a new method of delivering an analyte to a transmembrane pore in a membrane. The method involves the use of microparticles.

Abstract: The invention relates to improving the movement of a target polynucleotide with respect to a transmembrane pore when the movement is controlled by a polynucleotide binding protein.

Abstract: The invention relates to mutant forms of CsgG. The invention also relates to analyte detection and characterisation using CsgG.

Abstract: The invention relates to mutant forms of CsgG. The invention also relates to analyte detection and characterisation using CsgG.

Abstract: Arrangements are disclosed for measuring small electrical currents with high sensitivity, for example in the context of sensing molecular entities, for example via interactions between the molecular entities and a membrane protein inserted in an amphiphilic membrane. In one arrangement there is provided a current sensing circuit (52) configured to integrate the current output by a sensor element (56) during each of a plurality of sensing frames (62). In each sensing frame (62) first and second analogue samples of the integral are taken during first and second time windows (71,72). A readout circuit (54) processes the first and second analogue samples to output a digital output signal representing the current output by the sensor element (56). The processing comprises analogue to digital conversion processing and output processing. The output processing is performed exclusively during periods outside of the first and second time windows.

Abstract: The invention relates to a new method of determining the presence, absence or one or more characteristics of multiple analytes. The invention concerns coupling a first analyte to a membrane containing a detector and investigating the first analyte using the detector. The invention also concerns coupling a second analyte to the membrane and investigating the second analyte. The first analyte is uncoupled form the membrane prior to investigating the second analyte. The invention also relates to polynucleotide sequencing.