Objective Sequence-Based Subfamily Classifications of Mouse Homeodomains Reflect Their In Vitro DNA-Binding Preferences

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Objective Sequence-Based Subfamily Classifications of Mouse Homeodomains Reflect Their In Vitro DNA-Binding Preferences

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dc.contributor.author Santos, Miguel A.
dc.contributor.author Turinsky, Andrei L.
dc.contributor.author Ong, Serene
dc.contributor.author Tsai, Jennifer
dc.contributor.author Berger, Michael F.
dc.contributor.author Badis, Gwenael
dc.contributor.author Talukder, Shaheynoor
dc.contributor.author Gehrke, Andrew R.
dc.contributor.author Hughes, Timothy R.
dc.contributor.author Wodak, Shoshana J.
dc.contributor.author Bulyk, Martha Leonia
dc.date.accessioned 2011-03-19T21:01:05Z
dc.date.issued 2010
dc.identifier.citation Santos, Miguel A., Andrei L. Turinsky, Serene Ong, Jennifer Tsai, Michael F. Berger, Gwenael Badis, Shaheynoor Talukder, et al. 2010. Objective sequence-based subfamily classifications of mouse homeodomains reflect their in vitro DNA-binding preferences. Nucleic Acids Research 38, no. 22: 7927-7942. en_US
dc.identifier.issn 0305-1048 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4745743
dc.description.abstract Classifying proteins into subgroups with similar molecular function on the basis of sequence is an important step in deriving reliable functional annotations computationally. So far, however, available classification procedures have been evaluated against protein subgroups that are defined by experts using mainly qualitative descriptions of molecular function. Recently, in vitro DNA-binding preferences to all possible 8-nt DNA sequences have been measured for 178 mouse homeodomains using protein-binding microarrays, offering the unprecedented opportunity of evaluating the classification methods against quantitative measures of molecular function. To this end, we automatically derive homeodomain subtypes from the DNA-binding data and independently group the same domains using sequence information alone. We test five sequence-based methods, which use different sequence-similarity measures and algorithms to group sequences. Results show that methods that optimize the classification robustness reflect well the detailed functional specificity revealed by the experimental data. In some of these classifications, 73–83% of the subfamilies exactly correspond to, or are completely contained in, the function-based subtypes. Our findings demonstrate that certain sequence-based classifications are capable of yielding very specific molecular function annotations. The availability of quantitative descriptions of molecular function, such as DNA-binding data, will be a key factor in exploiting this potential in the future. en_US
dc.language.iso en_US en_US
dc.publisher Oxford University Press en_US
dc.relation.isversionof doi://10.1093/nar/gkq714 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001082/pdf/ en_US
dash.license LAA
dc.title Objective Sequence-Based Subfamily Classifications of Mouse Homeodomains Reflect Their In Vitro DNA-Binding Preferences en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Nucleic Acids Research en_US
dash.depositing.author Bulyk, Martha Leonia
dc.date.available 2011-03-19T21:01:05Z
dash.affiliation.other HMS^Pathology en_US
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US

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