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NoLogo: a new statistical model highlights the diversity and suggests new classes of Crm1-dependent nuclear export signals

BACKGROUND: Crm1-dependent Nuclear Export Signals (NESs) are clusters of alternating hydrophobic and non-hydrophobic amino acid residues between 10 to 15 amino acids in length. NESs were largely thought to follow simple consensus patterns, based on which they were categorized into 6–10 classes. Howe...

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Autores principales: Liku, Muluye E., Legere, Elizabeth-Ann, Moses, Alan M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828312/
https://www.ncbi.nlm.nih.gov/pubmed/29482494
http://dx.doi.org/10.1186/s12859-018-2076-7
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author Liku, Muluye E.
Legere, Elizabeth-Ann
Moses, Alan M.
author_facet Liku, Muluye E.
Legere, Elizabeth-Ann
Moses, Alan M.
author_sort Liku, Muluye E.
collection PubMed
description BACKGROUND: Crm1-dependent Nuclear Export Signals (NESs) are clusters of alternating hydrophobic and non-hydrophobic amino acid residues between 10 to 15 amino acids in length. NESs were largely thought to follow simple consensus patterns, based on which they were categorized into 6–10 classes. However, newly discovered NESs often deviate from the established consensus patterns. Thus, identifying NESs within protein sequences remains a bioinformatics challenge. RESULTS: We describe a probabilistic representation of NESs using a new generative model we call NoLogo that can account for a large diversity of NESs. Using this model to predict NESs, we demonstrate improved performance over PSSM and GLAM2 models, but do not achieve the performance of the state-of-the-art NES predictor LocNES. Our findings illustrate that over 30% of NESs are best described by novel NES classes rather than the 6–10 classes proposed by current/existing models. Finally, many NESs have additional hydrophobic residues either upstream or downstream of the canonical four residues, suggesting possible functionality. CONCLUSION: Applying the NoLogo model highlights the observation that NESs are more diverse than previously appreciated. Our work questions the practice of assigning each NES to one of several predefined NES classes. Finally, our analysis suggests a novel and testable biophysical perspective on interaction between Crm1 receptor and Crm1-dependent NESs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-018-2076-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-58283122018-02-28 NoLogo: a new statistical model highlights the diversity and suggests new classes of Crm1-dependent nuclear export signals Liku, Muluye E. Legere, Elizabeth-Ann Moses, Alan M. BMC Bioinformatics Methodology Article BACKGROUND: Crm1-dependent Nuclear Export Signals (NESs) are clusters of alternating hydrophobic and non-hydrophobic amino acid residues between 10 to 15 amino acids in length. NESs were largely thought to follow simple consensus patterns, based on which they were categorized into 6–10 classes. However, newly discovered NESs often deviate from the established consensus patterns. Thus, identifying NESs within protein sequences remains a bioinformatics challenge. RESULTS: We describe a probabilistic representation of NESs using a new generative model we call NoLogo that can account for a large diversity of NESs. Using this model to predict NESs, we demonstrate improved performance over PSSM and GLAM2 models, but do not achieve the performance of the state-of-the-art NES predictor LocNES. Our findings illustrate that over 30% of NESs are best described by novel NES classes rather than the 6–10 classes proposed by current/existing models. Finally, many NESs have additional hydrophobic residues either upstream or downstream of the canonical four residues, suggesting possible functionality. CONCLUSION: Applying the NoLogo model highlights the observation that NESs are more diverse than previously appreciated. Our work questions the practice of assigning each NES to one of several predefined NES classes. Finally, our analysis suggests a novel and testable biophysical perspective on interaction between Crm1 receptor and Crm1-dependent NESs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-018-2076-7) contains supplementary material, which is available to authorized users. BioMed Central 2018-02-27 /pmc/articles/PMC5828312/ /pubmed/29482494 http://dx.doi.org/10.1186/s12859-018-2076-7 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Methodology Article
Liku, Muluye E.
Legere, Elizabeth-Ann
Moses, Alan M.
NoLogo: a new statistical model highlights the diversity and suggests new classes of Crm1-dependent nuclear export signals
title NoLogo: a new statistical model highlights the diversity and suggests new classes of Crm1-dependent nuclear export signals
title_full NoLogo: a new statistical model highlights the diversity and suggests new classes of Crm1-dependent nuclear export signals
title_fullStr NoLogo: a new statistical model highlights the diversity and suggests new classes of Crm1-dependent nuclear export signals
title_full_unstemmed NoLogo: a new statistical model highlights the diversity and suggests new classes of Crm1-dependent nuclear export signals
title_short NoLogo: a new statistical model highlights the diversity and suggests new classes of Crm1-dependent nuclear export signals
title_sort nologo: a new statistical model highlights the diversity and suggests new classes of crm1-dependent nuclear export signals
topic Methodology Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828312/
https://www.ncbi.nlm.nih.gov/pubmed/29482494
http://dx.doi.org/10.1186/s12859-018-2076-7
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