The whole alignment and nothing but the alignment: the problem of spurious alignment flanks. Export

@article{citeulike:3293036, abstract = {Pairwise sequence alignment is a ubiquitous tool for inferring the evolution and function of DNA, RNA and protein sequences. It is therefore essential to identify alignments arising by chance alone, i.e. spurious alignments. On one hand, if an entire alignment is spurious, statistical techniques for identifying and eliminating it are well known. On the other hand, if only a part of the alignment is spurious, elimination is much more problematic. In practice, even the sizes and frequencies of spurious subalignments remain unknown. This article shows that some common scoring schemes tend to overextend alignments and generate spurious alignment flanks up to hundreds of base pairs/amino acids in length. In the UCSC genome database, e.g. spurious flanks probably comprise >18\% of the human-fugu genome alignment. To evaluate the possibility that chance alone generated a particular flank on a particular pairwise alignment, we provide a simple 'overalignment' P-value. The overalignment P-value can identify spurious alignment flanks, thereby eliminating potentially misleading inferences about evolution and function. Moreover, by explicitly demonstrating the tradeoff between over- and under-alignment, our methods guide the rational choice of scoring schemes for various alignment tasks.}, address = {Computational Biology Research Center, Institute for Advanced Industrial Science and Technology, Tokyo 135-0064, Japan and National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.}, author = {Frith, Martin C C. and Park, Yonil and Sheetlin, Sergey L L. and Spouge, John L L.}, citeulike-article-id = {3293036}, citeulike-linkout-0 = {http://dx.doi.org/10.1093/nar/gkn579}, citeulike-linkout-1 = {http://nar.oxfordjournals.org/cgi/content/abstract/36/18/5863}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18796526}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18796526}, day = {16}, doi = {10.1093/nar/gkn579}, issn = {1362-4962}, journal = {Nucleic acids research}, keywords = {alignment}, month = {September}, posted-at = {2008-11-29 15:50:24}, priority = {2}, title = {The whole alignment and nothing but the alignment: the problem of spurious alignment flanks.}, url = {http://dx.doi.org/10.1093/nar/gkn579}, year = {2008} }

TY - JOUR ID - citeulike:3293036 L3 - citeulike-article-id:3293036 N2 - Pairwise sequence alignment is a ubiquitous tool for inferring the evolution and function of DNA, RNA and protein sequences. It is therefore essential to identify alignments arising by chance alone, i.e. spurious alignments. On one hand, if an entire alignment is spurious, statistical techniques for identifying and eliminating it are well known. On the other hand, if only a part of the alignment is spurious, elimination is much more problematic. In practice, even the sizes and frequencies of spurious subalignments remain unknown. This article shows that some common scoring schemes tend to overextend alignments and generate spurious alignment flanks up to hundreds of base pairs/amino acids in length. In the UCSC genome database, e.g. spurious flanks probably comprise >18% of the human-fugu genome alignment. To evaluate the possibility that chance alone generated a particular flank on a particular pairwise alignment, we provide a simple 'overalignment' P-value. The overalignment P-value can identify spurious alignment flanks, thereby eliminating potentially misleading inferences about evolution and function. Moreover, by explicitly demonstrating the tradeoff between over- and under-alignment, our methods guide the rational choice of scoring schemes for various alignment tasks. JF - Nucleic acids research SN - 1362-4962 AD - Computational Biology Research Center, Institute for Advanced Industrial Science and Technology, Tokyo 135-0064, Japan and National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. TI - The whole alignment and nothing but the alignment: the problem of spurious alignment flanks. KW - alignment AU - Frith, Martin C AU - Park, Yonil AU - Sheetlin, Sergey L AU - Spouge, John L PY - 2008/09/16/ UR - http://dx.doi.org/10.1093/nar/gkn579 ER -