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Directing Experimental Biology: A Case Study in Mitochondrial Biogenesis
Computational approaches have promised to organize collections of functional genomics data into testable predictions of gene and protein involvement in biological processes and pathways. However, few such predictions have been experimentally validated on a large scale, leaving many bioinformatic met...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654405/ https://www.ncbi.nlm.nih.gov/pubmed/19300515 http://dx.doi.org/10.1371/journal.pcbi.1000322 |
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author | Hibbs, Matthew A. Myers, Chad L. Huttenhower, Curtis Hess, David C. Li, Kai Caudy, Amy A. Troyanskaya, Olga G. |
author_facet | Hibbs, Matthew A. Myers, Chad L. Huttenhower, Curtis Hess, David C. Li, Kai Caudy, Amy A. Troyanskaya, Olga G. |
author_sort | Hibbs, Matthew A. |
collection | PubMed |
description | Computational approaches have promised to organize collections of functional genomics data into testable predictions of gene and protein involvement in biological processes and pathways. However, few such predictions have been experimentally validated on a large scale, leaving many bioinformatic methods unproven and underutilized in the biology community. Further, it remains unclear what biological concerns should be taken into account when using computational methods to drive real-world experimental efforts. To investigate these concerns and to establish the utility of computational predictions of gene function, we experimentally tested hundreds of predictions generated from an ensemble of three complementary methods for the process of mitochondrial organization and biogenesis in Saccharomyces cerevisiae. The biological data with respect to the mitochondria are presented in a companion manuscript published in PLoS Genetics (doi:10.1371/journal.pgen.1000407). Here we analyze and explore the results of this study that are broadly applicable for computationalists applying gene function prediction techniques, including a new experimental comparison with 48 genes representing the genomic background. Our study leads to several conclusions that are important to consider when driving laboratory investigations using computational prediction approaches. While most genes in yeast are already known to participate in at least one biological process, we confirm that genes with known functions can still be strong candidates for annotation of additional gene functions. We find that different analysis techniques and different underlying data can both greatly affect the types of functional predictions produced by computational methods. This diversity allows an ensemble of techniques to substantially broaden the biological scope and breadth of predictions. We also find that performing prediction and validation steps iteratively allows us to more completely characterize a biological area of interest. While this study focused on a specific functional area in yeast, many of these observations may be useful in the contexts of other processes and organisms. |
format | Text |
id | pubmed-2654405 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-26544052009-03-20 Directing Experimental Biology: A Case Study in Mitochondrial Biogenesis Hibbs, Matthew A. Myers, Chad L. Huttenhower, Curtis Hess, David C. Li, Kai Caudy, Amy A. Troyanskaya, Olga G. PLoS Comput Biol Research Article Computational approaches have promised to organize collections of functional genomics data into testable predictions of gene and protein involvement in biological processes and pathways. However, few such predictions have been experimentally validated on a large scale, leaving many bioinformatic methods unproven and underutilized in the biology community. Further, it remains unclear what biological concerns should be taken into account when using computational methods to drive real-world experimental efforts. To investigate these concerns and to establish the utility of computational predictions of gene function, we experimentally tested hundreds of predictions generated from an ensemble of three complementary methods for the process of mitochondrial organization and biogenesis in Saccharomyces cerevisiae. The biological data with respect to the mitochondria are presented in a companion manuscript published in PLoS Genetics (doi:10.1371/journal.pgen.1000407). Here we analyze and explore the results of this study that are broadly applicable for computationalists applying gene function prediction techniques, including a new experimental comparison with 48 genes representing the genomic background. Our study leads to several conclusions that are important to consider when driving laboratory investigations using computational prediction approaches. While most genes in yeast are already known to participate in at least one biological process, we confirm that genes with known functions can still be strong candidates for annotation of additional gene functions. We find that different analysis techniques and different underlying data can both greatly affect the types of functional predictions produced by computational methods. This diversity allows an ensemble of techniques to substantially broaden the biological scope and breadth of predictions. We also find that performing prediction and validation steps iteratively allows us to more completely characterize a biological area of interest. While this study focused on a specific functional area in yeast, many of these observations may be useful in the contexts of other processes and organisms. Public Library of Science 2009-03-20 /pmc/articles/PMC2654405/ /pubmed/19300515 http://dx.doi.org/10.1371/journal.pcbi.1000322 Text en Hibbs et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Hibbs, Matthew A. Myers, Chad L. Huttenhower, Curtis Hess, David C. Li, Kai Caudy, Amy A. Troyanskaya, Olga G. Directing Experimental Biology: A Case Study in Mitochondrial Biogenesis |
title | Directing Experimental Biology: A Case Study in Mitochondrial Biogenesis |
title_full | Directing Experimental Biology: A Case Study in Mitochondrial Biogenesis |
title_fullStr | Directing Experimental Biology: A Case Study in Mitochondrial Biogenesis |
title_full_unstemmed | Directing Experimental Biology: A Case Study in Mitochondrial Biogenesis |
title_short | Directing Experimental Biology: A Case Study in Mitochondrial Biogenesis |
title_sort | directing experimental biology: a case study in mitochondrial biogenesis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654405/ https://www.ncbi.nlm.nih.gov/pubmed/19300515 http://dx.doi.org/10.1371/journal.pcbi.1000322 |
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