Gene Splicing Defects
OwnerWilliam Fairbrotherinventor
Life of this patent
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Abstract
Predicting the effect of a mutation in a nucleic acid sequence on splicing is accomplished by determining the distance between at least two nucleic acid sequence positional distributions and providing a prediction of impact on splicing function based on at least the distance. A low distance indicates there is little or no difference in splicing function compared to a normal control. A high distance indicates a difference in splicing function. Related apparatus, systems, techniques and articles are also described.
Claims47
A method of predicting the effect of a mutation, in a nucleic acid sequence on splicing, the method comprising:
- determining a distance between at least two nucleic acid sequence positional distributions;
- providing a prediction of impact on splicing function based on at least the distance, wherein a low distance indicates there is little or no difference in splicing function compared to a normal control, and wherein a high distance indicates a difference in splicing function.
A non-transitory computer readable storage medium comprising executable instructions to:
- receive data characterizing a first nucleic acid sequence, a second nucleic acid sequence, a positional distribution of the first sequence relative to a splice site, and a positional distribution of the second sequence relative to the splice site;
- compute a distance between the positional distribution of the first sequence and the positional distribution of the second sequence, the second sequence being a mutation of the first sequence;
- and
- provide the distance.
A tangible computer readable medium including instructions that, when executed by a computer, cause the computer to:
- create alignments of nucleotides surrounding all 3′ and 5′ splice sites;
- count the number of occurrences of all polymers;
- construct, for each polymer, a feature vector by concatenating counts from the 3′ splice site alignment and the 5′ splice site alignment;
- normalize the counts in each entry of each feature vector;
- cluster the feature vectors;
- and
- determine the number of clusters.
A method for identifying a candidate subject for repair of a gene splicing defect associated with a pathological condition, comprising
- providing a plurality of nucleic acid sequences obtained from or derived from an individual or a gene mutation database sequence and at least one corresponding mutation for each nucleic acid sequence;
- providing a positional distribution of each of the plurality of nucleic acid sequences and the at least one corresponding mutation;
- determining a distance between each of the nucleic acid sequence positional distributions and the at least one corresponding mutation positional distribution, wherein a low distance indicates there is little or no difference in splicing function, and wherein a high distance indicates a splicing mutation in the nucleic acid sequence and identifies said individual as a candidate for repair of said gene splicing defect.
Dependencies are inferred from the claim text.