The invention relates to methods and devices for analyzing single molecules, i.e. nucleic acids. Such single molecules may be derived from natural samples, such as cells, tissues, soil, air and water without separating or enriching individual components. In certain aspects of the invention, the meth
The invention relates to methods and devices for analyzing single molecules, i.e. nucleic acids. Such single molecules may be derived from natural samples, such as cells, tissues, soil, air and water without separating or enriching individual components. In certain aspects of the invention, the methods and devices are useful in performing nucleic acid sequence analysis by probe hybridization.
대표청구항▼
1. A system for determining sequence information for a polynucleotide, comprising: (a) an array of DNA molecules, wherein each DNA molecule comprises a fragment of said polynucleotide;(b) a set of informative oligonucleotide probes, wherein each probe comprises a label and a nucleotide sequence comp
1. A system for determining sequence information for a polynucleotide, comprising: (a) an array of DNA molecules, wherein each DNA molecule comprises a fragment of said polynucleotide;(b) a set of informative oligonucleotide probes, wherein each probe comprises a label and a nucleotide sequence comprising the formula NxByNz, wherein: (i) each N is independently a degenerate base;(ii) each B is independently an informative base;(iii) x and z are each at least one; and(iv) y is 2 to 20;(c) a detector configured to detect labeled probes from said set once the probes have hybridized to DNA molecules in the array, and to send data indicating the labeled probes that have been detected to a computer processor; and(d) a computer processor programmed to receive said data from the detector, and to process the data to obtain said sequence information for the polynucleotide. 2. The system of claim 1, wherein the detector is a megapixel CCD camera. 3. The system of claim 2, wherein said DNA molecules are arrayed at a density of about 1 molecule per CCD pixel. 4. The system of claim 1, wherein each DNA molecule comprises multiple copies of the respective fragment. 5. The system of claim 1, wherein y is 2 to 8. 6. The system of claim 1, wherein the labels are fluorescent labels. 7. The system of claim 1, wherein the DNA molecules on the array comprise overlapping fragments of an entire human genome. 8. The system of claim 1, wherein the DNA molecules are arrayed on a support in a grid pattern. 9. A system for determining sequence information for a polynucleotide, comprising: (a) an array of DNA molecules, wherein each DNA molecule comprises a fragment of said polynucleotide;(b) a first set of informative oligonucleotide probes, wherein each probe comprises a label and a nucleotide sequence comprising the formula NxBy or the formula ByNz, wherein: (i) each N is independently a degenerate base;(ii) each B is independently an informative base;(iii) x and z are each at least one; and(iv) y is 2 to 20;(c) a detector configured to detect labeled probes from said set once the probes have hybridized to DNA molecules in the array, and to send data indicating the labeled probes that have been detected to a computer processor; and(d) a computer processor programmed to receive said data from the detector, and to process the data to obtain said sequence information for the polynucleotide. 10. The system of claim 9, wherein each probe of the set comprises the formula NxBy. 11. The system of claim 9, wherein each probe of the set comprises the formula ByNz. 12. The system of claim 9, further comprising: (e) a second set of oligonucleotides; and(f) a ligase for ligating an oligonucleotide probe from the first set to an oligonucleotide from the second set when hybridized to adjacent sites on a DNA molecule on the array. 13. The system of claim 12, wherein the first set of probes is a universal probe set. 14. The system of claim 9, wherein x is 1 to 4. 15. The system of claim 9, wherein y is 2 to 8. 16. The system of claim 9, wherein y is 4 to 5. 17. The system of claim 9, wherein z is 1 to 4. 18. The system of claim 9, wherein the labels are fluorescent labels. 19. The system of claim 9, wherein each DNA molecule comprises multiple copies of the respective fragment. 20. The system of claim 9, wherein the DNA molecules on the array comprise overlapping fragments of an entire human genome. 21. The system of claim 9, wherein the DNA molecules are arrayed on a support in a grid pattern. 22. A product for determining sequence information for a polynucleotide, comprising: (a) an array of DNA molecules, wherein each DNA molecule comprises a fragment of said polynucleotide; and(b) oligonucleotide probes hybridized to a plurality of the DNA molecules on the array, said probes constituting a first set wherein each probe comprises a label and a nucleotide sequence comprising the formula NxBy or the formula ByNz, wherein: (i) each N is independently a degenerate base;(ii) each B is independently an informative base;(iii) x and z are each at least one; and(iv) y is 2 to 20. 23. The product of claim 22, wherein each probe of the first set comprises the formula NxBy. 24. The product of claim 22, wherein each probe of the first set comprises the formula ByNz. 25. The product of claim 22, further comprising a second set of oligonucleotides each hybridized to one of the DNA molecules at a position that is adjacent to an oligonucleotide probe of the first set. 26. The product of claim 25, wherein said oligonucleotides from the second set are each ligated to the adjacent probe from the first set. 27. The product of claim 22, wherein x is 1 to 4. 28. The product of claim 22, wherein y is 2 to 8. 29. The product of claim 22, wherein y is 4 to 5. 30. The product of claim 22, wherein z is 1 to 4. 31. The product of claim 22, wherein the labels are a fluorescent labels. 32. The product of claim 22 wherein each DNA molecule comprises multiple copies of the respective fragment. 33. The product of claim 22, wherein the DNA molecules on the array comprise overlapping fragments of an entire human genome. 34. The product of claim 22, wherein the DNA molecules are arrayed on a support in a grid pattern. 35. The product of claim 22, wherein probes in the first set comprise the formula NxByNz. 36. A system for determining sequence information for a polynucleotide, comprising: (a) an array of DNA molecules, wherein each DNA molecule comprises a fragment of said polynucleotide;(b) a first set of informative oligonucleotide probes, wherein each probe comprises a label and a nucleotide sequence comprising the formula NxBy or the formula ByNz, wherein: (i) each N is independently a degenerate base;(ii) each B is independently an informative base; and(iii) x, y, and z are each at least one;(c) a second set of oligonucleotide probes, each configured to bind to a site in a DNA molecule of the array adjacent to a probe from the first set;(d) a detector configured to detect labeled probes from said set once the probes have hybridized to DNA molecules in the array, and to send data indicating the labeled probes that have been detected to a computer processor; and(e) a computer processor programmed to receive said data from the detector, and to process the data to obtain said sequence information for the polynucleotide. 37. The system of claim 36, further comprising a ligase for ligating an oligonucleotide probe from the first set to an oligonucleotide from the second set when hybridized to adjacent sites on a DNA molecule on the array. 38. The system of claim 36, wherein probes in the first set comprise the formula NxByNz. 39. The system of claim 36, wherein y is 2 to 8. 40. The system of claim 36, wherein the DNA molecules on the array comprise overlapping fragments of an entire human genome. 41. A product for determining sequence information for a polynucleotide, comprising: (a) an array of DNA molecules, wherein each DNA molecule comprises a fragment of said polynucleotide; and(b) oligonucleotide probes hybridized to a plurality of the DNA molecules on the array, said probes constituting a first set wherein each probe comprises a label and a nucleotide sequence comprising the formula NxBy or the formula ByNz, wherein: (i) each N is independently a degenerate base;(ii) each B is independently an informative base;(iii) x, y, and z are each at least one; and(c) a second set of oligonucleotides each hybridized to a plurality of the DNA molecules at a position that is adjacent to an oligonucleotide probe of the first set. 42. The product of claim 41, wherein oligonucleotides from the second set that are hybridized to the DNA molecules are ligated to an adjacent probe from the first set. 43. The product of claim 41, wherein probes in the first set comprise the formula NxByNz. 44. The product of claim 41, wherein y is 2 to 8. 45. The product of claim 41, wherein the DNA molecules on the array comprise overlapping fragments of an entire human genome.
연구과제 타임라인
LOADING...
LOADING...
LOADING...
LOADING...
LOADING...
이 특허에 인용된 특허 (70)
Barany, Francis; Liu, Jianzhao; Kirk, Brian W.; Zirvi, Monib; Gerry, Norman P.; Paty, Philip B., Accelerating identification of single nucleotide polymorphisms and alignment of clones in genomic sequencing.
Birkenmeyer Larry G. (Chicago IL) Carrino John J. (Gurnee IL) Dille Bruce J. (Antioch IL) Hu Hsiang-Yun (Libertyville IL) Kratochvil Jon D. (Kenosha WI) Laffler Thomas G. (Libertyville IL) Marshall R, Amplification of target nucleic acids using gap filling ligase chain reaction.
Barany, Francis; Gerry, Norman P.; Witowski, Nancy E.; Day, Joseph; Hammer, Robert P.; Barany, George, Detection of nucleic acid sequence differences using the ligase detection reaction with addressable arrays.
Whiteley Norman M. (San Carlos CA) Hunkapiller Michael W. (San Carlos CA) Glazer Alexander N. (Orinda CA), Detection of specific sequences in nucleic acids.
Pirrung Michael C. (Durham NC) Read J. Leighton (Palo Alto CA) Fodor Stephen P. A. (Palo Alto CA) Stryer Lubert (Stanford CA), Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof.
Albrecht Glenn ; Brenner Sydney,GBX ; DuBridge Robert B. ; Lloyd David H. ; Pallas Michael C., Massively parallel signature sequencing by ligation of encoded adaptors.
Adams Christopher P. (Winter Hill MA) Kron Stephen Joseph (Boston MA), Method for performing amplification of nucleic acid with two primers bound to a single solid support.
Drmanac Radoje T. (Zvecanska 46 Beograd 11000) Crkvenjakov Radomir B. (Bulevar JNA 118 Beograd YUX 11000), Method of sequencing of genomes by hybridization of oligonucleotide probes.
Brennan Thomas M. (2000 Broadway ; No. 705 San Francisco CA 94115) Heyneker Herbert L. (360 Forest Ave. ; No. 506 Palo Alto CA 94301), Methods and compositions for determining the sequence of nucleic acids.
Drmanac Radoje T. ; Drmanac Snezana ; Hou Aaron ; Hauser Brian, Methods for sequencing repetitive sequences and for determining the order of sequence subfragments.
Heller Michael J. (Encinitas CA) Tu Eugene (San Diego CA) Butler William F. (Carlsbad CA), Molecular biological diagnostic systems including electrodes.
Urdea Michael S. (Alamo CA) Warner Brian (Martinez CA) Horn Thomas (Berkeley CA), Nucleic acid multimers and amplified nucleic acid hybridization assays using same.
Newman Peter J. (Shorewood WI) Aster Richard H. (Milwaukee WI), Polymorphism of human platelet membrane glycoprotein IIIa and diagnostic and therapeutic applications thereof.
Rabbani,Elazar; Stavrianopoulos,Jannis G.; Kirtikar,Dollie; Johnston,Kenneth H.; Thalenfeld,Barbara E., System, array and non-porous solid support comprising fixed or immobilized nucleic acids.
Bell, H. Randall; Pettit, John W; Landers, James P; Bienvenue, Joan M; Marchiarullo, Daniel J; Root, Brian E; Scott, Orion N, Optical approach for microfluidic DNA electrophoresis detection.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.