Abstract: The present invention provides a method of detecting mutational signatures in a DNA sample. The invention relates to method of detecting signatures arising from rearrangements in the DNA in the sample and determining the contributions of known rearrangement signatures to said rearrangements. In particular embodiments, the contributions are determined by computing the cosine similarity between the rearrangement mutations in said catalogue and the rearrangement mutational signatures. The rearrangement signatures are classified based on whether they are clustered or not, whether they are tandem duplications, deletions, inversions or translocations and on the basis of their size.

Abstract: A culture medium is provided which is capable of establishing expanded potential stem cell (EPSC) lines which resemble naïve or ground state ES cells, but are also able to differentiate into placenta trophoblasts and the embryo proper. Methods are provided using the medium for the in vitro conversion and maintenance of cells, including pluripotent cells into EPSCs.

Abstract: The present invention concerns methods of diagnosing and/or prognostication of non-alcoholic fatty liver disease (NAFLD) or alcohol-related fatty liver disease (ARLD) in a subject, wherein said methods comprise detecting somatic mutations in DNA, RNA and/or protein that confer a selective advantage on one or more liver cells of the subject. The present invention also provides methods for identifying subjects suffering from NAFLD or ARLD who would benefit from treatment with a therapeutic agent and/or identifying subjects suffering from NAFLD or ARLD who would benefit from increased disease monitoring. The present invention also provides therapeutic agents that find utility in the treatment of NAFLD or ARLD.

Abstract: The invention relates to therapeutic compositions comprising at least one isolated bacterium and a pharmaceutically acceptable excipient, as well as methods of preparing such therapeutic compositions. The therapeutic compositions find application in the treatment of dysbiosis, in particular dysbiosis of the gastrointestinal tract.

Abstract: Described herein is a method of sequencing a template that comprises a direct repeat, comprising: (a) in the same reaction, hybridizing a primer to a first site that is upstream of the first repeat sequence and hybridizing a primer to a second site that is upstream of the second repeat sequence, wherein the first and second sites are: (i) upstream of the first and second repeat sequences, respectively, and (ii) equidistant from the first and second repeat sequences; and (b) subjecting the hybridization product of (a) to a sequencing-by-synthesis sequencing reaction to produce a sequence read that comprises a combination of the first and second repeat sequences.

Abstract: A method, for the identification of bacterial isolates suitable for use in bacteriotherapy, the method comprising: (i) preparing a suspension of material collected from a host harbouring microbiota; (ii) addition of an activator of bacterial spores sufficient to allow growth of bacteria from spores present in the suspension; (iii) culturing the suspension; and (iv) identification of at least one bacterial species within the culture.

Abstract: Described herein is a population of direct repeat molecules, where each molecule of the population contains a direct repeat composed of sequences that are amplified from the opposite strands of a double-stranded fragment of genomic DNA. Within each molecule, the first repeat (referred to as TOP) is amplified from the one strand of a double-stranded fragment of genomic DNA and the second repeat (referred to as BOT?) is amplified from the other strand of the same fragment of double-stranded fragment of genomic DNA.

Abstract: The invention relates to a nucleic acid construct for bi-allelic conditional modification of a target gene and methods of use thereof.

Abstract: A culture medium is provided which is capable of establishing expanded potential stem cell (EPSC) lines which resemble naive or ground state ES cells, but are also able to differentiate into placenta trophoblasts and the embryo proper. Methods are provided using the medium for the in vitro conversion and maintenance of cells, including pluripotent cells into EPSCs.

Abstract: The present invention provides a method of detecting mutational signatures in a DNA sample. The invention relates to method of detecting signatures arising from rearrangements in the DNA in the sample and determining the contributions of known rearrangement signatures to said rearrangements. In particular embodiments, the contributions are determined by computing the cosine similarity between the rearrangement mutations in said catalogue and the rearrangement mutational signatures. The rearrangement signatures are classified based on whether they are clustered or not, whether they are tandem duplications, deletions, inversions or translocations and on the basis of their size.

Abstract: A method, for the identification of bacterial isolates suitable for use in bacteriotherapy, the method comprising: (i) preparing a suspension of material collected from a host harboring microbiota; (ii) addition of an activator of bacterial spores sufficient to allow growth of bacteria from spores present in the suspension; (iii) culturing the suspension; and (iv) identification of at least one bacterial species within the culture.

Abstract: Methods are provided of using a database that stores a plurality of reference genomes and phylogenetic information which relates the stored reference genomes to each other in a phylogenetic structure. These methods are useful in analysing the bacteria and/or bacterial lineages present in a sample and to identify a bacterium for use in therapy.

Abstract: Reprogrammed somatic cells, methods for reprogramming, reprogramming factors for somatic cells and uses of such factors and cells are described. Nuclear reprogramming factors [NRF] described comprise one or more of a gene product or a polynucleic acid encoding a gene product from a retinoic acid receptor (RAR/RXR) family member, or an agonist or antagonist thereof; a gene product from an Lrh1 family member; or an agonist thereof; retinoic acid or a gene product involved in synthesizing or metabolizing retinoic acid; or an agonist or antagonist thereof; or a gene product that is involved in transporting a retinoic acid family member.

Abstract: Immunogenic compositions and vaccines against Plasmodial infection comprising an Rh polypeptide or a fragment or variant thereof are disclosed. Also disclosed are Rh5 polypeptides or fragments or variants thereof capable of binding CD147 and conferring protection against infection and/or disease caused by multiple Plasmodial strains or Plasmodial species, inhibitors of the interaction between Rh5 and CD147 and methods for producing polypeptides in a mammalian expression system.

Abstract: The present disclosure includes methods for manipulation of the genome, to products obtained or obtainable from such methods, and uses of these products.

Abstract: A monitoring method comprising identifying a somatically acquired genomic rearrangement associated with a disease state in a patient by genome-wide analysis of the nucleic acid of that patient and monitoring the changes in levels of nucleic acid containing the genomic rearrangement, and/or quantifying the levels of nucleic acid containing the genomic rearrangement as a marker for the progression or severity of a disease in that patient is described. Use of a monitoring process of the invention in assessment of efficacy of a therapy and use of a patient specific genomic rearrangement as a biomarker for disease progression in that patient are also described.

Abstract: Method of producing induced T-to-Natural-Killer [ITNK] cells, target T cells and/or target pro-T cells from T cells and/or pro-T cells which method involves modulating the activity and/or effect of at least one Bcl11b gene and/or protein present in a T cell and/or pro-T cell, and converting said T cell and/or pro-T cell to an ITNK cell or target Tcells and/or target pro-T cells is described. ITNK cells, target T cells and/or target pro-T cells produced by such method and mature activated T cells in which Bcl11b expression is downregulated or absent, and the use of such cells or modulators of Bcl11b in medicine is also described.

Abstract: The invention relates to a polypeptide or part thereof which inhibits the apoptotic activity of the tumor suppressor protein p53, and includes screening methods to identify agents which interfere with the activity of the polypeptide.

Abstract: The invention relates to a polypeptide or part thereof which inhibits the apoptotic activity of the tumor suppressor protein p53, and includes screening methods to identify agents which interfere with the activity of the polypeptide.