Abstract: Provided herein, among other things, is method for analyzing a planar biological sample. In some embodiments, the method may comprise: contacting an oligonucleotide or a conjugate comprising the same with a planar biological sample under conditions by which the oligonucleotide or conjugate specifically binds to sites in or on the sample; performing one or more steps to release and/or extend the oligonucleotide in situ, to produce a reporter probe; transferring the reporter probe from the sample to a planar support that does not comprise an array of oligonucleotides, in a way that preserves the spatial relationship of the reporter probe in the sample; and detecting the reporter probe on the support.

Abstract: This disclosure provides, inter alia, a probe system probe system for analyzing a nucleic acid sample. In some embodiments, the probe system may comprise: a set of identifier oligonucleotides of sequence B, a set of splint oligonucleotides of formula X?-A?-B?-Z?, wherein sequence A? is complementary to a genomic fragment and sequence B? is complementary to at least one member of the set of identifier oligonucleotides, and one or more probe sequences comprising X and Z. Each splint oligonucleotide is capable of hybridizing to the probe sequences, a member of the set of identifier oligonucleotides and a genomic fragment, thereby producing a ligatable complex of formula X-A-B-Z. The probe system can be used to identify a chromosome aneuploidy in cell free DNA, for example.

Abstract: This disclosure provides, inter alia, a probe system probe system for analyzing a nucleic acid sample. In some embodiments, the probe system may comprise: a set of identifier oligonucleotides of sequence B, a set of splint oligonucleotides of formula X?-A?-B?-Z?, wherein sequence A? is complementary to a genomic fragment and sequence B? is complementary to at least one member of the set of identifier oligonucleotides, and one or more probe sequences comprising X and Z. Each splint oligonucleotide is capable of hybridizing to the probe sequences, a member of the set of identifier oligonucleotides and a genomic fragment, thereby producing a ligatable complex of formula X-A-B-Z. The probe system can be used to identify a chromosome aneuploidy in cell free DNA, for example.

Abstract: This disclosure provides, inter alia, a probe system probe system for analyzing a nucleic acid sample. In some embodiments, the probe system may comprise: a set of identifier oligonucleotides of sequence B, a set of splint oligonucleotides of formula X?-A?-B?-Z?, wherein sequence A? is complementary to a genomic fragment and sequence B? is complementary to at least one member of the set of identifier oligonucleotides, and one or more probe sequences comprising X and Z. Each splint oligonucleotide is capable of hybridizing to the probe sequences, a member of the set of identifier oligonucleotides and a genomic fragment, thereby producing a ligatable complex of formula X-A-B-Z. The probe system can be used to identify a chromosome aneuploidy in cell free DNA, for example.

Abstract: A method of estimating the amount of a methylated locus is provided. In certain embodiments the method comprises: digesting a nucleic acid sample that contains both unmethylated and methylated copies of a genomic locus with an MspJI family member to produce a population of fragments that are in the range of 20-40 nucleotides in length, ligating adaptor sequence A and adaptor sequence B to the respective ends of a target fragment of sequence X, and quantifying the amount of ligation products of formula A-X-B. A kit for performing the method is also provided.

Abstract: This disclosure provides, inter alia, a probe system probe system for analyzing a nucleic acid sample. In some embodiments, the probe system may comprise: a set of identifier oligonucleotides of sequence B, a set of splint oligonucleotides of formula X?-A?-B?-Z?, wherein sequence A? is complementary to a genomic fragment and sequence B? is complementary to at least one member of the set of identifier oligonucleotides, and one or more probe sequences comprising X and Z. Each splint oligonucleotide is capable of hybridizing to the probe sequences, a member of the set of identifier oligonucleotides and a genomic fragment, thereby producing a ligatable complex of formula X-A-B-Z. The probe system can be used to identify a chromosome aneuploidy in cell free DNA, for example.

Abstract: Provided herein, among other things, is a method of processing a nucleic acid sample. In some embodiments, the method comprises a) hybridizing a sample comprising a target fragment to a nucleic acid probe comprising: i. a head sequence and a tail sequence, wherein the head and tail sequences are at the ends of a first oligonucleotide molecule; and ii.

Abstract: Provided herein, among other things, is a method of processing a nucleic acid sample. In some embodiments, the method comprises a) hybridizing a sample comprising a target fragment to a nucleic acid probe comprising: i. a head sequence and a tail sequence, wherein the head and tail sequences are at the ends of a first oligonucleotide molecule; and ii.

Abstract: Described herein is a new approach in which a nucleic acid species of interest (e.g. a chromosome) containing multiple unique target sequences is detected using multiple specific probes that are amplified by rolling circle amplification and detected. Multiple probes are used to provide a detectable signal, where the magnitude of the signal is proportional to the number of probes recognising their target sequences. Individual signals from the plurality of probes are converted into a single cumulative detectable signal, amplifying the individual signals through the multiplex probing. Ten or more probes produce a signal amplification of ten-fold or more. The generated signals depend on correctly reacted probes upon target recognition, using sequence specific hybridisation and enzymatic catalysis to generate specific products from which the signal is obtained.

Abstract: This disclosure provides, inter alia, a probe system probe system for analyzing a nucleic acid sample. In some embodiments, the probe system may comprise: a set of identifier oligonucleotides of sequence B, a set of splint oligonucleotides of formula X?-A?-B?-Z?, wherein sequence A? is complementary to a genomic fragment and sequence B? is complementary to at least one member of the set of identifier oligonucleotides, and one or more probe sequences comprising X and Z. Each splint oligonucleotide is capable of hybridizing to the probe sequences, a member of the set of identifier oligonucleotides and a genomic fragment, thereby producing a ligatable complex of formula X-A-B-Z. The probe system can be used to identify a chromosome aneuploidy in cell free DNA, for example.

Abstract: Described herein is a new approach in which a nucleic acid species of interest (e.g. a chromosome) containing multiple unique target sequences is detected using multiple specific probes that are amplified by rolling circle amplification and detected. Multiple probes are used to provide a detectable signal, where the magnitude of the signal is proportional to the number of probes recognising their target sequences. Individual signals from the plurality of probes are converted into a single cumulative detectable signal, amplifying the individual signals through the multiplex probing. Ten or more probes produce a signal amplification of ten-fold or more. The generated signals depend on correctly reacted probes upon target recognition, using sequence specific hybridisation and enzymatic catalysis to generate specific products from which the signal is obtained.

Abstract: This disclosure provides, inter alia, a probe system probe system for analyzing a nucleic acid sample. In some embodiments, the probe system may comprise: a set of identifier oligonucleotides of sequence B, a set of splint oligonucleotides of formula X?-A?-B?-Z?, wherein sequence A? is complementary to a genomic fragment and sequence B? is complementary to at least one member of the set of identifier oligonucleotides, and one or more probe sequences comprising X and Z. Each splint oligonucleotide is capable of hybridizing to the probe sequences, a member of the set of identifier oligonucleotides and a genomic fragment, thereby producing a ligatable complex of formula X-A-B-Z. The probe system can be used to identify a chromosome aneuploidy in cell free DNA, for example.

Abstract: Provided herein, among other things, is a method of processing a nucleic acid sample. In some embodiments, the method comprises a) hybridizing a sample comprising a target fragment to a nucleic acid probe comprising: i. a head sequence and a tail sequence, wherein the head and tail sequences are at the ends of a first oligonucleotide molecule; and ii.

Abstract: A method of estimating the amount of a methylated locus is provided. In certain embodiments the method comprises: digesting a nucleic acid sample that contains both unmethylated and methylated copies of a genomic locus with an MspJI family member to produce a population of fragments that are in the range of 20-40 nucleotides in length, ligating adaptor sequence A and adaptor sequence B to the respective ends of a target fragment of sequence X, and quantifying the amount of ligation products of formula A-X-B. A kit for performing the method is also provided.

Abstract: Provided herein, among other things, is a method of processing a nucleic acid sample. In some embodiments, the method comprises a) hybridizing a sample comprising a target fragment to a nucleic acid probe comprising: i. a head sequence and a tail sequence, wherein the head and tail sequences are at the ends of a first oligonucleotide molecule; and ii.

Abstract: A method of estimating the amount of a methylated locus is provided. In certain embodiments the method comprises: digesting a nucleic acid sample that contains both unmethylated and methylated copies of a genomic locus with an MspJI family member to produce a population of fragments that are in the range of 20-40 nucleotides in length, ligating adaptor sequence A and adaptor sequence B to the respective ends of a target fragment of sequence X, and quantifying the amount of ligation products of formula A-X-B. A kit for performing the method is also provided.

Abstract: This disclosure provides, inter alia, a probe system probe system for analyzing a nucleic acid sample. In some embodiments, the probe system may comprise: a set of identifier oligonucleotides of sequence B, a set of splint oligonucleotides of formula X?-A?-B?-Z?, wherein sequence A? is complementary to a genomic fragment and sequence B? is complementary to at least one member of the set of identifier oligonucleotides, and one or more probe sequences comprising X and Z. Each splint oligonucleotide is capable of hybridizing to the probe sequences, a member of the set of identifier oligonucleotides and a genomic fragment, thereby producing a ligatable complex of formula X-A-B-Z. The probe system can be used to identify a chromosome aneuploidy in cell free DNA, for example.

Abstract: Provided herein, among other things, is a method of processing a nucleic acid sample. In some embodiments, the method comprises a) hybridizing a sample comprising a target fragment to a nucleic acid probe comprising: i. a head sequence and a tail sequence, wherein the head and tail sequences are at the ends of a first oligonucleotide molecule; and ii.

Abstract: Described herein is a new approach in which a nucleic acid species of interest (e.g. a chromosome) containing multiple unique target sequences is detected using multiple specific probes that are amplified by rolling circle amplification and detected. Multiple probes are used to provide a detectable signal, where the magnitude of the signal is proportional to the number of probes recognising their target sequences. Individual signals from the plurality of probes are converted into a single cumulative detectable signal, amplifying the individual signals through the multiplex probing. Ten or more probes produce a signal amplification of ten-fold or more. The generated signals depend on correctly reacted probes upon target recognition, using sequence specific hybridisation and enzymatic catalysis to generate specific products from which the signal is obtained.

Abstract: This disclosure provides a method for adding an adaptor to a genomic sequence by invasive cleavage, as well as a kit for performing the method. In some embodiments, the method comprises: a) hybridizing genomic DNA to an adaptor comprising a double stranded region and a single stranded region comprising a 5? overhang to produce a substrate for a flap endonuclease; b) cleaving the substrate using the flap endonuclease; c) ligating the recessed end of the double stranded region to the fragment to produce an adaptor-ligated DNA; d) intramolecularly ligating the ends of the adaptor-ligated DNA to produce a circular DNA molecule; and e) enzymatically processing the circular DNA molecule using an oligonucleotide that hybridizes to the adaptor and an enzyme. A kit for performing the method is also provided.