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Combining evidence using p-values: application to sequence homology searches.
Abstract
MOTIVATION: To illustrate an intuitive and statistically valid method for combining independent sources of evidence that yields a p-value for the complete evidence, and to apply it to the problem of detecting simultaneous matches to multiple patterns in sequence homology searches. RESULTS: In sequence analysis, two or more (approximately) independent measures of the membership of a sequence (or sequence region) in some class are often available. We would like to estimate the likelihood of the sequence being a member of the class in view of all the available evidence. An example is estimating the significance of the observed match of a macromolecular sequence (DNA or protein) to a set of patterns (motifs) that characterize a biological sequence family. An intuitive way to do this is to express each piece of evidence as a p-value, and then use the product of these p-values as the measure of membership in the family. We derive a formula and algorithm (QFAST) for calculating the statistical distribution of the product of n independent p-values. We demonstrate that sorting sequences by this p-value effectively combines the information present in multiple motifs, leading to highly accurate and sensitive sequence homology searches.
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“The occurrence of this promoter sequence was validated in ~ 85% (357) of cases using the MAST software (Bailey & Gribskov, 1998), which also provided evidences for an additional 10 sites not initially included in the MEME constructed motif, for a grand total of 432 motif-associated TSSs (Fig 3C and…”
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Metadata
- Authors
- Bailey, T. L., & Gribskov, M.
- Venue
- Bioinformatics
- Publisher
- Oxford University Press (OUP)
- Published
- 1998-01-01
- Volume
- 14
- Issue
- 1
- Pages
- 48-54
- ISSN
- 1367-4803 (ISSN-L)
- 1367-4811
- OpenAlex
- W2131510173
- Cited by
- 1,253
- References
- 0
- FWCI
- 4.73
- Type
- journal article
- Language
- en
- Open access
- closed
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