Methods and computer software for detecting splice variants
First Claim
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1. A method of identifying one or more alternative splicing events for one or more genes of a target genome using a plurality of exon array, each array comprising a plurality of nucleic acid probe sets having one or more nucleic acid probes that are complementary to at least a portion of an exon and do not comprise junction probes, and a computer system comprising at least one processor, a memory, and an interface, the method comprising:
- providing the plurality of exon arrays, wherein a nucleic acid probe set in each exon array is designed to probe for at least a portion of a first probe selection region (PSR) corresponding to an exon derived from one or more input annotations for the target genome, wherein a nucleic acid probe set associated with the first PSR is included in a first gene expression level grouping of a first gene on the target genome and the exon corresponding to the PSR maps to the first gene;
hybridizing the plurality of nucleic acid probes of a first exon array to nucleic acids derived from one or more nucleic acid samples from a first tissue sample to generate first probe selection region (PSR) intensity data corresponding to the nucleic acid probe set associated with the first;
calculating a first normalized exon intensity comprising a ratio of first exon intensity data to a first gene expression level, wherein the first exon intensity data comprises data from the first PSR intensity data corresponding to the exon, and the first gene expression level comprises a first gene intensity value obtained from PSR intensity data assembled from nucleic acid probes associated with the first gene expression level grouping;
hybridizing the plurality of nucleic acid probes of a second exon array to nucleic acids derived from one or more nucleic acid samples from a second tissue sample to generate second probe selection region (PSR) intensity data corresponding to the nucleic acid probe set associated with the first PSR;
calculating a second normalized exon intensity comprising a ratio of second exon intensity data to a second gene expression level, wherein the second exon intensity data comprises data from the second PSR intensity data, and the second gene expression level comprises a second gene intensity value obtained from PSR intensity data assembled from nucleic acid probes associated with the first gene expression level grouping; and
detecting differential exon expression of the gene using the first and second normalized exon intensities.
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Abstract
Methods and software products for analysis of alternative splicing are disclosed. In general the methods involve normalizing probe set or exon intensity to an expression level measurement of the gene. The methods may be used to identify tissue-specific alternative splicing events.
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21 Claims
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1. A method of identifying one or more alternative splicing events for one or more genes of a target genome using a plurality of exon array, each array comprising a plurality of nucleic acid probe sets having one or more nucleic acid probes that are complementary to at least a portion of an exon and do not comprise junction probes, and a computer system comprising at least one processor, a memory, and an interface, the method comprising:
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providing the plurality of exon arrays, wherein a nucleic acid probe set in each exon array is designed to probe for at least a portion of a first probe selection region (PSR) corresponding to an exon derived from one or more input annotations for the target genome, wherein a nucleic acid probe set associated with the first PSR is included in a first gene expression level grouping of a first gene on the target genome and the exon corresponding to the PSR maps to the first gene; hybridizing the plurality of nucleic acid probes of a first exon array to nucleic acids derived from one or more nucleic acid samples from a first tissue sample to generate first probe selection region (PSR) intensity data corresponding to the nucleic acid probe set associated with the first; calculating a first normalized exon intensity comprising a ratio of first exon intensity data to a first gene expression level, wherein the first exon intensity data comprises data from the first PSR intensity data corresponding to the exon, and the first gene expression level comprises a first gene intensity value obtained from PSR intensity data assembled from nucleic acid probes associated with the first gene expression level grouping; hybridizing the plurality of nucleic acid probes of a second exon array to nucleic acids derived from one or more nucleic acid samples from a second tissue sample to generate second probe selection region (PSR) intensity data corresponding to the nucleic acid probe set associated with the first PSR; calculating a second normalized exon intensity comprising a ratio of second exon intensity data to a second gene expression level, wherein the second exon intensity data comprises data from the second PSR intensity data, and the second gene expression level comprises a second gene intensity value obtained from PSR intensity data assembled from nucleic acid probes associated with the first gene expression level grouping; and detecting differential exon expression of the gene using the first and second normalized exon intensities. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21)
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Specification