Systems and methods for sequencing by hybridization
AssigneeBrown University Research Foundation
InventorsFranco P. Preparata, Eliezer Upfal, John S. Oliver
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Abstract
The systems and methods described herein relate to nucleic acid probes comprising a pattern of universal and designate nucleotides (or analogs thereof), or ‘gapped’ probes, and the use of sets of gapped probes in sequencing by hybridization to determine the sequence of nucleic acid sequences. The inclusion of universal nucleotides in the probes allows for efficient and rapid sequencing of longer nucleotide sequences than can be sequenced using traditional probes. The systems and methods described herein also relate to apparatus for sequencing nucleic acids which include gapped probes, as well as computer systems capable of analyzing data generated using gapped probes in such apparatus.
Claims21
A gapped probe, comprising a sequence of universal and designate nucleotides and/or nucleotide analogs ordered in a predetermined pattern, wherein the pattern has a reduced shift-overlap count such that no shifted count is greater than 60% of the perfect count.
A gapped probe, comprising a sequence of universal and designate nucleotides and/or nucleotide analogs ordered in a pattern, wherein the pattern comprises a root and an iterated unit, and wherein the length of the root is identical to the length of the iterated unit, and wherein the probe comprises at least one nucleotide analog selected from the group consisting of:
- a peptide nucleic acid, pyranosyl-RNA, a hexitol nucleic acid, a mannitol nucleic acid, an altritol nucleic acid, a 2′–5′ nucleic acid, a locked nucleic acid, a seco-locked nucleic acid, a bicyclo-DNA, a bicyclo[3.3.0]DNA, a tricyclo-DNA, 3-hydroxy-N-acetylprolinol substituted nucleic acid, a carbocyclic nucleic acid, a carbocyclic/bicyclic nucleic acid, a nucleic acid with a triazole backbone, a nucleic acid with an imidazole backbone, a 1-phenylserinol nucleic acid, a nucleic acid with an alpha anomer backbone, and a metal-linked nucleic acid.
A set of gapped probes, comprising a plurality of instances of a sequence of universal and designate nucleotides and/or nucleotide analogs ordered in a predetermined pattern, wherein the pattern has a reduced shift-overlap count such that no shifted count is greater than 60% of the perfect count.
A probe array, comprising a substrate, and a set of gapped probes disposed thereon, wherein each probe comprises an instance of a predetermined pattern of universal and designate nucleotides and/or nucleotide analogs such that the set comprises a plurality of instances of the pattern, wherein the predetermined pattern has a reduced shift-overlap count such that no shifted count is greater than 60% of the perfect count.
Dependencies are inferred from the claim text.