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Science 25 January 2008:
Vol. 319. no. 5862, pp. 473 - 476
DOI: 10.1126/science.1151532
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Reports

Alignment Uncertainty and Genomic Analysis

Karen M. Wong,1 Marc A. Suchard,2 John P. Huelsenbeck3*

The statistical methods applied to the analysis of genomic data do not account for uncertainty in the sequence alignment. Indeed, the alignment is treated as an observation, and all of the subsequent inferences depend on the alignment being correct. This may not have been too problematic for many phylogenetic studies, in which the gene is carefully chosen for, among other things, ease of alignment. However, in a comparative genomics study, the same statistical methods are applied repeatedly on thousands of genes, many of which will be difficult to align. Using genomic data from seven yeast species, we show that uncertainty in the alignment can lead to several problems, including different alignment methods resulting in different conclusions.

1 Section of Ecology, Behavior and Evolution, University of California, San Diego, La Jolla, CA 92093, USA.
2 Department of Biomathematics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
3 Department of Integrative Biology, University of California, Berkeley, Berkeley, CA 94720, USA.

* To whom correspondence should be addressed. E-mail: johnh{at}berkeley.edu

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