Methods for identifying suitable nucleic acid probe sequences for use in nucleic acid arrays
First Claim
1. A method of identifying a sequence of a nucleic acid that is suitable for use as a substrate surface immobilized probe for a target nucleic acid, said method comprising:
- (a) identifying a plurality of candidate probe sequences for said target nucleic acid based on at least one selection criterion;
(b) empirically evaluating each of said candidate probe sequences under a plurality of different experimental sets to obtain a collection of empirical data values for each of said candidate nucleic acid probe sequences for each of said plurality of different experimental sets;
(c) clustering said candidate probe sequences into one or more groups of candidate probe sequences based on each candidate probe sequence'"'"'s collection of empirical data values, wherein each of said one or more groups exhibits substantially the same performance across said plurality of experimental sets;
(d) selecting one of said one or more groups based on at least one criterion; and
(e) choosing a candidate probe sequence from said selected group to as said sequence of said nucleic acid that is suitable for use as a substrate immobilized probe for said target nucleic acid.
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Abstract
Methods of identifying a sequence of a probe, e.g., a biopolymeric probe, such as a nucleic acid, that is suitable for use as a surface immobilized probe for a target molecule of interest, e.g., a target nucleic acid, are provided. A feature of the subject methods is that a set of computationally determined initial candidate sequences are empirically evaluated to obtain functional data that is then employed to identify one or more clusters of candidate probe sequences from the initial set such that all candidate probe sequences within each identified cluster exhibitsubstantially the same performance under a plurality of different experiments, specifically a plurality of differential gene expression experiments. A candidate probe from the cluster that exhibits the best performance across the plurality of experimental sets is then selected as the optimum candidate probe, e.g., based on one or more performance metrics. The subject invention also includes algorithms for performing the subject methods recorded on a computer readable medium, as well as computational analysis systems that include the same. Also provided are nucleic acid arrays produced with probes having sequences identified by the subject methods, as well as methods for using the same.
35 Citations
25 Claims
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1. A method of identifying a sequence of a nucleic acid that is suitable for use as a substrate surface immobilized probe for a target nucleic acid, said method comprising:
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(a) identifying a plurality of candidate probe sequences for said target nucleic acid based on at least one selection criterion;
(b) empirically evaluating each of said candidate probe sequences under a plurality of different experimental sets to obtain a collection of empirical data values for each of said candidate nucleic acid probe sequences for each of said plurality of different experimental sets;
(c) clustering said candidate probe sequences into one or more groups of candidate probe sequences based on each candidate probe sequence'"'"'s collection of empirical data values, wherein each of said one or more groups exhibits substantially the same performance across said plurality of experimental sets;
(d) selecting one of said one or more groups based on at least one criterion; and
(e) choosing a candidate probe sequence from said selected group to as said sequence of said nucleic acid that is suitable for use as a substrate immobilized probe for said target nucleic acid. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25)
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Specification