Ecogenomic perspectives on domains of unknown function: correlation-based exploration of marine metagenomes.
<h4>Background</h4>The proportion of conserved DNA sequences with no clear function is steadily growing in bioinformatics databases. Studies of sequence and structural homology have indicated that many uncharacterized protein domain sequences are variants of functionally described domain...
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oai:doaj.org-article:d389fb0ab8994cb0b2e1aa53874a9cd82021-11-18T07:53:31ZEcogenomic perspectives on domains of unknown function: correlation-based exploration of marine metagenomes.1932-620310.1371/journal.pone.0050869https://doaj.org/article/d389fb0ab8994cb0b2e1aa53874a9cd82013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23516388/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The proportion of conserved DNA sequences with no clear function is steadily growing in bioinformatics databases. Studies of sequence and structural homology have indicated that many uncharacterized protein domain sequences are variants of functionally described domains. If these variants promote an organism's ecological fitness, they are likely to be conserved in the genome of its progeny and the population at large. The genetic composition of microbial communities in their native ecosystems is accessible through metagenomics. We hypothesize the co-variation of protein domain sequences across metagenomes from similar ecosystems will provide insights into their potential roles and aid further investigation.<h4>Methodology/principal findings</h4>We calculated the correlation of Pfam protein domain sequences across the Global Ocean Sampling metagenome collection, employing conservative detection and correlation thresholds to limit results to well-supported hits and associations. We then examined intercorrelations between domains of unknown function (DUFs) and domains involved in known metabolic pathways using network visualization and cluster-detection tools. We used a cautious "guilty-by-association" approach, referencing knowledge-level resources to identify and discuss associations that offer insight into DUF function. We observed numerous DUFs associated to photobiologically active domains and prevalent in the Cyanobacteria. Other clusters included DUFs associated with DNA maintenance and repair, inorganic nutrient metabolism, and sodium-translocating transport domains. We also observed a number of clusters reflecting known metabolic associations and cases that predicted functional reclassification of DUFs.<h4>Conclusion/significance</h4>Critically examining domain covariation across metagenomic datasets can grant new perspectives on the roles and associations of DUFs in an ecological setting. Targeted attempts at DUF characterization in the laboratory or in silico may draw from these insights and opportunities to discover new associations and corroborate existing ones will arise as more large-scale metagenomic datasets emerge.Pier Luigi ButtigiegWolfgang HankelnIvaylo KostadinovRenzo KottmannPelin YilmazMelissa Beth DuhaimeFrank Oliver GlöcknerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e50869 (2013) |
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Medicine R Science Q Pier Luigi Buttigieg Wolfgang Hankeln Ivaylo Kostadinov Renzo Kottmann Pelin Yilmaz Melissa Beth Duhaime Frank Oliver Glöckner Ecogenomic perspectives on domains of unknown function: correlation-based exploration of marine metagenomes. |
description |
<h4>Background</h4>The proportion of conserved DNA sequences with no clear function is steadily growing in bioinformatics databases. Studies of sequence and structural homology have indicated that many uncharacterized protein domain sequences are variants of functionally described domains. If these variants promote an organism's ecological fitness, they are likely to be conserved in the genome of its progeny and the population at large. The genetic composition of microbial communities in their native ecosystems is accessible through metagenomics. We hypothesize the co-variation of protein domain sequences across metagenomes from similar ecosystems will provide insights into their potential roles and aid further investigation.<h4>Methodology/principal findings</h4>We calculated the correlation of Pfam protein domain sequences across the Global Ocean Sampling metagenome collection, employing conservative detection and correlation thresholds to limit results to well-supported hits and associations. We then examined intercorrelations between domains of unknown function (DUFs) and domains involved in known metabolic pathways using network visualization and cluster-detection tools. We used a cautious "guilty-by-association" approach, referencing knowledge-level resources to identify and discuss associations that offer insight into DUF function. We observed numerous DUFs associated to photobiologically active domains and prevalent in the Cyanobacteria. Other clusters included DUFs associated with DNA maintenance and repair, inorganic nutrient metabolism, and sodium-translocating transport domains. We also observed a number of clusters reflecting known metabolic associations and cases that predicted functional reclassification of DUFs.<h4>Conclusion/significance</h4>Critically examining domain covariation across metagenomic datasets can grant new perspectives on the roles and associations of DUFs in an ecological setting. Targeted attempts at DUF characterization in the laboratory or in silico may draw from these insights and opportunities to discover new associations and corroborate existing ones will arise as more large-scale metagenomic datasets emerge. |
format |
article |
author |
Pier Luigi Buttigieg Wolfgang Hankeln Ivaylo Kostadinov Renzo Kottmann Pelin Yilmaz Melissa Beth Duhaime Frank Oliver Glöckner |
author_facet |
Pier Luigi Buttigieg Wolfgang Hankeln Ivaylo Kostadinov Renzo Kottmann Pelin Yilmaz Melissa Beth Duhaime Frank Oliver Glöckner |
author_sort |
Pier Luigi Buttigieg |
title |
Ecogenomic perspectives on domains of unknown function: correlation-based exploration of marine metagenomes. |
title_short |
Ecogenomic perspectives on domains of unknown function: correlation-based exploration of marine metagenomes. |
title_full |
Ecogenomic perspectives on domains of unknown function: correlation-based exploration of marine metagenomes. |
title_fullStr |
Ecogenomic perspectives on domains of unknown function: correlation-based exploration of marine metagenomes. |
title_full_unstemmed |
Ecogenomic perspectives on domains of unknown function: correlation-based exploration of marine metagenomes. |
title_sort |
ecogenomic perspectives on domains of unknown function: correlation-based exploration of marine metagenomes. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doaj.org/article/d389fb0ab8994cb0b2e1aa53874a9cd8 |
work_keys_str_mv |
AT pierluigibuttigieg ecogenomicperspectivesondomainsofunknownfunctioncorrelationbasedexplorationofmarinemetagenomes AT wolfganghankeln ecogenomicperspectivesondomainsofunknownfunctioncorrelationbasedexplorationofmarinemetagenomes AT ivaylokostadinov ecogenomicperspectivesondomainsofunknownfunctioncorrelationbasedexplorationofmarinemetagenomes AT renzokottmann ecogenomicperspectivesondomainsofunknownfunctioncorrelationbasedexplorationofmarinemetagenomes AT pelinyilmaz ecogenomicperspectivesondomainsofunknownfunctioncorrelationbasedexplorationofmarinemetagenomes AT melissabethduhaime ecogenomicperspectivesondomainsofunknownfunctioncorrelationbasedexplorationofmarinemetagenomes AT frankoliverglockner ecogenomicperspectivesondomainsofunknownfunctioncorrelationbasedexplorationofmarinemetagenomes |
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