PhenoMeter: a metabolome database search tool using statistical similarity matching of metabolic phenotypes for high-confidence detection of functional links

This article describes PhenoMeter, a new type of metabolomics database search that accepts metabolite response patterns as queries and searches the MetaPhen database of reference patterns for responses that are statistically significantly similar or inverse for the purposes of detecting functional l...

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Main Authors: Adam James Carroll, Peng eZhang, Lynne eWhitehead, Sarah eKaines, Guillaume eTcherkez, Murray Ronald Badger
Format: Article
Language:English
Published: Frontiers Media S.A. 2015-07-01
Series:Frontiers in Bioengineering and Biotechnology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fbioe.2015.00106/full
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author Adam James Carroll
Peng eZhang
Lynne eWhitehead
Sarah eKaines
Guillaume eTcherkez
Murray Ronald Badger
author_facet Adam James Carroll
Peng eZhang
Lynne eWhitehead
Sarah eKaines
Guillaume eTcherkez
Murray Ronald Badger
author_sort Adam James Carroll
collection DOAJ
description This article describes PhenoMeter, a new type of metabolomics database search that accepts metabolite response patterns as queries and searches the MetaPhen database of reference patterns for responses that are statistically significantly similar or inverse for the purposes of detecting functional links. To identify a similarity measure that would detect functional links as reliably as possible, we compared the performance of four statistics in correctly top-matching metabolic phenotypes of Arabidopsis thaliana metabolism mutants affected in different steps of the photorespiration metabolic pathway to reference phenotypes of mutants affected in the same enzymes by independent mutations. The best performing statistic, the PhenoMeter Score (PM Score), was a function of both Pearson correlation and Fisher’s Exact Test of directional overlap. This statistic outperformed Pearson correlation, biweight midcorrelation and Fisher’s Exact Test used alone. To demonstrate general applicability, we show that the PhenoMeter reliably retrieved the most closely functionally-linked response in the database when queried with responses to a wide variety of environmental and genetic perturbations. Attempts to match metabolic phenotypes between independent studies were met with varying success and possible reasons for this are discussed. Overall, our results suggest that integration of pattern-based search tools into metabolomics databases will aid functional annotation of newly recorded metabolic phenotypes analogously to the way sequence similarity search algorithms have aided the functional annotation of genes and proteins. PhenoMeter is freely available at MetabolomeExpress (https://www.metabolome-express.org/phenometer.php).
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spelling doaj.art-f19666e9086f4a2db6ab9b7303bec3522022-12-22T01:58:37ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852015-07-01310.3389/fbioe.2015.00106153550PhenoMeter: a metabolome database search tool using statistical similarity matching of metabolic phenotypes for high-confidence detection of functional linksAdam James Carroll0Peng eZhang1Lynne eWhitehead2Sarah eKaines3Guillaume eTcherkez4Murray Ronald Badger5The Australian National UniversityThe Australian National UniversityThe Australian National UniversityThe Australian National UniversityThe Australian National UniversityThe Australian National UniversityThis article describes PhenoMeter, a new type of metabolomics database search that accepts metabolite response patterns as queries and searches the MetaPhen database of reference patterns for responses that are statistically significantly similar or inverse for the purposes of detecting functional links. To identify a similarity measure that would detect functional links as reliably as possible, we compared the performance of four statistics in correctly top-matching metabolic phenotypes of Arabidopsis thaliana metabolism mutants affected in different steps of the photorespiration metabolic pathway to reference phenotypes of mutants affected in the same enzymes by independent mutations. The best performing statistic, the PhenoMeter Score (PM Score), was a function of both Pearson correlation and Fisher’s Exact Test of directional overlap. This statistic outperformed Pearson correlation, biweight midcorrelation and Fisher’s Exact Test used alone. To demonstrate general applicability, we show that the PhenoMeter reliably retrieved the most closely functionally-linked response in the database when queried with responses to a wide variety of environmental and genetic perturbations. Attempts to match metabolic phenotypes between independent studies were met with varying success and possible reasons for this are discussed. Overall, our results suggest that integration of pattern-based search tools into metabolomics databases will aid functional annotation of newly recorded metabolic phenotypes analogously to the way sequence similarity search algorithms have aided the functional annotation of genes and proteins. PhenoMeter is freely available at MetabolomeExpress (https://www.metabolome-express.org/phenometer.php).http://journal.frontiersin.org/Journal/10.3389/fbioe.2015.00106/fullMetabolomicspattern recognitionPhenomicsData Interpretation, StatisticalSearch algorithmmetabolic Phenotyping
spellingShingle Adam James Carroll
Peng eZhang
Lynne eWhitehead
Sarah eKaines
Guillaume eTcherkez
Murray Ronald Badger
PhenoMeter: a metabolome database search tool using statistical similarity matching of metabolic phenotypes for high-confidence detection of functional links
Frontiers in Bioengineering and Biotechnology
Metabolomics
pattern recognition
Phenomics
Data Interpretation, Statistical
Search algorithm
metabolic Phenotyping
title PhenoMeter: a metabolome database search tool using statistical similarity matching of metabolic phenotypes for high-confidence detection of functional links
title_full PhenoMeter: a metabolome database search tool using statistical similarity matching of metabolic phenotypes for high-confidence detection of functional links
title_fullStr PhenoMeter: a metabolome database search tool using statistical similarity matching of metabolic phenotypes for high-confidence detection of functional links
title_full_unstemmed PhenoMeter: a metabolome database search tool using statistical similarity matching of metabolic phenotypes for high-confidence detection of functional links
title_short PhenoMeter: a metabolome database search tool using statistical similarity matching of metabolic phenotypes for high-confidence detection of functional links
title_sort phenometer a metabolome database search tool using statistical similarity matching of metabolic phenotypes for high confidence detection of functional links
topic Metabolomics
pattern recognition
Phenomics
Data Interpretation, Statistical
Search algorithm
metabolic Phenotyping
url http://journal.frontiersin.org/Journal/10.3389/fbioe.2015.00106/full
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