Abstract: Described herein is a complex comprising multiple nucleic acid molecules that are hybridized together, each comprising, from 5? to 3?, a first complementary sequence, a spacer sequence and a second complementary sequence, and either/or a 5? end sequence that is 5? of the first complementary sequence and terminates in a 5? phosphate and a 3? end sequence that is 3? of the second complementary sequence and terminates in a 3? hydroxyl. In this complex: the first complementary sequence of one molecule is directly or indirectly hybridized with the second complementary sequence of another molecule in the complex and the spacer sequence and the 3? and/or 5? end sequences are single-stranded. Methods of making and using the complex are also provided.

Abstract: Described herein is a complex comprising multiple nucleic acid molecules that are hybridized together, each comprising, from 5? to 3?, a first complementary sequence, a spacer sequence and a second complementary sequence, and either/or a 5? end sequence that is 5? of the first complementary sequence and terminates in a 5? phosphate and a 3? end sequence that is 3? of the second complementary sequence and terminates in a 3? hydroxyl. In this complex: the first complementary sequence of one molecule is directly or indirectly hybridized with the second complementary sequence of another molecule in the complex and the spacer sequence and the 3? and/or 5? end sequences are single-stranded. Methods of making and using the complex are also provided.

Abstract: Provided herein is a method for mapping rolling circle amplification (RCA) products that contain unique identifier sequences. The method generally involves (a) producing a complex comprising population of grid oligonucleotide molecules and a population of RCA products that each have a unique RCA product identifier sequence, wherein the grid oligonucleotides are hybridized directly or indirectly via a splint to complementary sites in the RCA products; (b) extending the grid oligonucleotide molecules that are hybridized to two RCA products to add the complements of the unique RCA product identifier sequences from the two RCA products to the grid oligonucleotide molecules; (c) sequencing the extended grid oligonucleotides; (d) analyzing the sequences to identify which pairs of unique RCA product identifier sequence complements have been added onto the grid oligonucleotides; and (e) making one or more physical maps of the immobilized RCA products using the pairs of sequences identified in (d).

Abstract: Provided herein is probe system comprising: a population of nucleic acid molecules that have an extendible end, a first set of barcoded particles that each have a nucleotide sequence comprising: (i) a binding sequence that is complementary to the extendible end of the nucleic acid molecules, (ii) a unique particle identifier sequence, and (iii) a first template sequence, and a second set of barcoded particles that each have a nucleotide sequence comprising: (i) the first template sequence and (ii) a unique particle identifier sequence. In use, extension of the nucleic acid molecules using the first set of barcoded particles of as a template produces extensions products that contain the complement of a unique particle identifier sequence of a particle and the complement of the first template sequence. Methods of using the probe system to map binding events in or on a cellular sample are also provided.

Abstract: Provided herein is probe system comprising: a population of nucleic acid molecules that have an extendible end, a first set of barcoded particles that each have a nucleotide sequence comprising: (i) a binding sequence that is complementary to the extendible end of the nucleic acid molecules, (ii) a unique particle identifier sequence, and (iii) a first template sequence, and a second set of barcoded particles that each have a nucleotide sequence comprising: (i) the first template sequence and (ii) a unique particle identifier sequence. In use, extension of the nucleic acid molecules using the first set of barcoded particles of as a template produces extensions products that contain the complement of a unique particle identifier sequence of a particle and the complement of the first template sequence. Methods of using the probe system to map binding events in or on a cellular sample are also provided.

Abstract: Provided herein is a method for making a physical map of a population of barcoded particles. In some embodiments, the method may involve: producing a complex comprising: i. a population of barcoded particles, wherein the barcoded particles are uniquely barcoded by surface-tethered oligonucleotides that have unique particle identifier sequences; and ii. a population of bridging moieties that comprises oligonucleotide sequences; wherein the bridging moieties are hybridized directly or indirectly to complementary sites in the surface-tethered oligonucleotides; performing a ligation, polymerization and/or a gap-fill/ligation reaction on the complex, thereby producing reaction products that comprise pairs of unique particle identifier sequences or complements thereof from adjacent barcoded particles: sequencing the reaction products, analyzing the sequences to making one or more physical maps of the barcoded particles. Systems for practicing the method are also provided.

Abstract: Described herein is a complex comprising multiple nucleic acid molecules that are hybridized together, each comprising, from 5? to 3?, a first complementary sequence, a spacer sequence and a second complementary sequence, and either/or a 5? end sequence that is 5? of the first complementary sequence and terminates in a 5? phosphate and a 3? end sequence that is 3? of the second complementary sequence and terminates in a 3? hydroxyl. In this complex: the first complementary sequence of one molecule is directly or indirectly hybridized with the second complementary sequence of another molecule in the complex and the spacer sequence and the 3? and/or 5? end sequences are single-stranded. Methods of making and using the complex are also provided.

Abstract: Provided herein is probe system comprising: a population of nucleic acid molecules that have an extendible end. a first set of barcoded particles that each have a nucleotide sequence comprising: (i) a binding sequence that is complementary to the extendible end of the nucleic acid molecules. (ii) a unique particle identifier sequence. and (iii) a first template sequence. and a second set of barcoded particles that each have a nucleotide sequence comprising: (i) the first template sequence and (ii) a unique particle identifier sequence. In use. extension of the nucleic acid molecules using the first set of barcoded particles of as a template produces extensions products that contain the complement of a unique particle identifier sequence of a particle and the complement of the first template sequence. Methods of using the probe system to map binding events in or on a cellular sample are also provided.

Abstract: A therapeutic agent capable of binding to the receptor CLPTM1 at the surface of an immune cell and modulating its activity for use in modulating the activity of the immune system to treat cancer, wherein the therapeutic agent is capable of inhibiting the growth and/or viability of an anti-inflammatory and/or immunosuppressive cell to relieve unwanted or deleterious immunosuppression by eliminating anti-inflammatory and/or immunosuppressive immune cells; and/or the therapeutic agent is capable of stimulating an antigen-presenting immune cell and acts to stimulate antigen-presenting immune cells to activate an anti-cancer immune response.

Abstract: Provided herein is a method for mapping rolling circle amplification (RCA) products that contain unique identifier sequences. The method generally involves (a) producing a complex comprising population of grid oligonucleotide molecules and a population of RCA products that each have a unique RCA product identifier sequence, wherein the grid oligonucleotides are hybridized directly or indirectly via a splint to complementary sites in the RCA products; (b) extending the grid oligonucleotide molecules that are hybridized to two RCA products to add the complements of the unique RCA product identifier sequences from the two RCA products to the grid oligonucleotide molecules; (c) sequencing the extended grid oligonucleotides; (d) analyzing the sequences to identify which pairs of unique RCA product identifier sequence complements have been added onto the grid oligonucleotides; and (e) making one or more physical maps of the immobilized RCA products using the pairs of sequences identified in (d).

Abstract: The invention relates to apolypeptide capable of binding to TGF-? for use in treating or preventing a condition associated with elevated or unwanted levels of TGF-?, wherein said polypeptide is capable of inhibiting the interaction of TGF-? with the receptor CLPTM1.

Abstract: The present invention provides a plurality of pairs of proximity probes, each pair being capable of binding to a different target analyte, wherein the first and second proximity probes of each pair of probes comprise universal oligonucleotides conjugated to their analyte binding moieties, and hybridised to the universal oligonucleotides are different tag oligonucleotides comprising universal complement domains common to all tag oligonucleotides and unique domains unique to each tag oligonucleotide, as well as methods for their production.

Abstract: The present invention relates to a proximity probe based detection assay (“proximity assay”) for an analyte in a sample, specifically a proximity probe extension assay (PEA), an in particular to an improvement in the method to reduce non-specific “background” signals, wherein the improvement comprises the use in such assays of a component comprising 3? exonuclease activity, said method comprising: (a) contacting said sample with at least one set of at least first and second proximity probes, which probes each comprise an analyte-binding domain and a nucleic acid domain and can simultaneously bind to the analyte; (b) allowing the nucleic acid domains of the proximity probes to interact with each other upon binding of said proximity probes to said analyte, wherein said interaction comprises the formation of a duplex; (c) contacting said sample with a component comprising 3? exonuclease activity; (d) extending the 3? end of at least one nucleic acid domain of said duplex to generate an extension product, wherein

Abstract: A therapeutic agent capable of binding to the receptor CLPTM1 at the surface of an immune cell and modulating its activity for use in modulating the activity of the immune system to treat cancer, wherein the therapeutic agent is capable of inhibiting the growth and/or viability of an anti-inflammatory and/or immunosuppressive cell to relieve unwanted or deleterious immunosuppression by eliminating anti-inflammatory and/or immunosuppressive immune cells; and/or the therapeutic agent is capable of stimulating an antigen-presenting immune cell and acts to stimulate antigen-presenting immune cells to activate an anti-cancer immune response.

Abstract: The invention relates to apolypeptide capable of binding to TGF-? for use in treating or preventing a condition associated with elevated or unwanted levels of TGF-?, wherein said polypeptide is capable of inhibiting the interaction of TGF-? with the receptor CLPTM1.

Abstract: The present invention providesabinding agent capable of binding to the extracellular domain of CLPTM1 for use in the treatment or prevention of a condition which is responsive to, or benefits from, (i) immunosuppression, (ii) the reduction or reversal of one or more pro-inflammatory cytokines or the induction of an anti-inflammatory cytokine), (iii) an increase in insulin sensitivity, or (iv) therapy with GDF15 and/or TGF-? and/or IFN?, wherein said binding agent has an EC 50 value of 1 ?g/ml or less when determined by measuring binding to membrane-permeabilised O-876 cells expressing native CLPTM1 by flow cytometry, and wherein said binding agent is not a natural ligand for CLPTM.

Abstract: The present invention provides a plurality of pairs of proximity probes, each pair being capable of binding to a different target analyte, wherein the first and second proximity probes of each pair of probes comprise universal oligonucleotides conjugated to their analyte binding moieties, and hybridised to the universal oligonucleotides are different tag oligonucleotides comprising universal complement domains common to all tag oligonucleotides and unique domains unique to each tag oligonucleotide, as well as methods for their production.