Sexual Dimorphism, Age, and Fat Mass Are Key Phenotypic Drivers of Proteomic Signatures

Aoife M Curran, Colleen Fogarty Draper, Marie-Pier Scott-Boyer, Armand Valsesia, Helen M Roche, Miriam F Ryan, Michael J. Gibney, Martina Kutmon, Chris T Evelo, Susan L Coort, Arne Astrup, Wim H Saris, Lorraine Brennan, Jim Kaput

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Validated protein biomarkers are needed for assessing health trajectories, predicting and subclassifying disease, and optimizing diagnostic and therapeutic clinical decision-making. The sensitivity, specificity, accuracy, and precision of single or combinations of protein biomarkers may be altered by differences in physiological states limiting the ability to translate research results to clinically useful diagnostic tests. Aptamer based affinity assays were used to test whether low abundant serum proteins differed based on age, sex, and fat mass in a healthy population of 94 males and 102 females from the MECHE cohort. The findings were replicated in 217 healthy male and 377 healthy female participants in the DiOGenes consortium. Of the 1129 proteins in the panel, 141, 51, and 112 proteins (adjusted p < 0.1) were identified in the MECHE cohort and significantly replicated in DiOGenes for sexual dimorphism, age, and fat mass, respectively. Pathway analysis classified a subset of proteins from the 3 phenotypes to the complement and coagulation cascades pathways and to immune and coagulation processes. These results demonstrated that specific proteins were statistically associated with dichotomous (male vs female) and continuous phenotypes (age, fat mass), which may influence the identification and use of biomarkers of clinical utility for health diagnosis and therapeutic strategies.

Original languageEnglish
Pages (from-to)4122-4133
Number of pages12
JournalJournal of Proteome Research
Volume16
Issue number11
DOIs
Publication statusPublished - 3 Nov 2017

Keywords

  • Journal Article

Cite this

Curran, A. M., Fogarty Draper, C., Scott-Boyer, M-P., Valsesia, A., Roche, H. M., Ryan, M. F., ... Kaput, J. (2017). Sexual Dimorphism, Age, and Fat Mass Are Key Phenotypic Drivers of Proteomic Signatures. Journal of Proteome Research, 16(11), 4122-4133. https://doi.org/10.1021/acs.jproteome.7b00501
Curran, Aoife M ; Fogarty Draper, Colleen ; Scott-Boyer, Marie-Pier ; Valsesia, Armand ; Roche, Helen M ; Ryan, Miriam F ; Gibney, Michael J. ; Kutmon, Martina ; Evelo, Chris T ; Coort, Susan L ; Astrup, Arne ; Saris, Wim H ; Brennan, Lorraine ; Kaput, Jim. / Sexual Dimorphism, Age, and Fat Mass Are Key Phenotypic Drivers of Proteomic Signatures. In: Journal of Proteome Research. 2017 ; Vol. 16, No. 11. pp. 4122-4133.
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Curran, AM, Fogarty Draper, C, Scott-Boyer, M-P, Valsesia, A, Roche, HM, Ryan, MF, Gibney, MJ, Kutmon, M, Evelo, CT, Coort, SL, Astrup, A, Saris, WH, Brennan, L & Kaput, J 2017, 'Sexual Dimorphism, Age, and Fat Mass Are Key Phenotypic Drivers of Proteomic Signatures', Journal of Proteome Research, vol. 16, no. 11, pp. 4122-4133. https://doi.org/10.1021/acs.jproteome.7b00501

Sexual Dimorphism, Age, and Fat Mass Are Key Phenotypic Drivers of Proteomic Signatures. / Curran, Aoife M; Fogarty Draper, Colleen; Scott-Boyer, Marie-Pier; Valsesia, Armand; Roche, Helen M; Ryan, Miriam F; Gibney, Michael J.; Kutmon, Martina; Evelo, Chris T; Coort, Susan L; Astrup, Arne; Saris, Wim H; Brennan, Lorraine; Kaput, Jim.

In: Journal of Proteome Research, Vol. 16, No. 11, 03.11.2017, p. 4122-4133.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Sexual Dimorphism, Age, and Fat Mass Are Key Phenotypic Drivers of Proteomic Signatures

AU - Curran, Aoife M

AU - Fogarty Draper, Colleen

AU - Scott-Boyer, Marie-Pier

AU - Valsesia, Armand

AU - Roche, Helen M

AU - Ryan, Miriam F

AU - Gibney, Michael J.

AU - Kutmon, Martina

AU - Evelo, Chris T

AU - Coort, Susan L

AU - Astrup, Arne

AU - Saris, Wim H

AU - Brennan, Lorraine

AU - Kaput, Jim

PY - 2017/11/3

Y1 - 2017/11/3

N2 - Validated protein biomarkers are needed for assessing health trajectories, predicting and subclassifying disease, and optimizing diagnostic and therapeutic clinical decision-making. The sensitivity, specificity, accuracy, and precision of single or combinations of protein biomarkers may be altered by differences in physiological states limiting the ability to translate research results to clinically useful diagnostic tests. Aptamer based affinity assays were used to test whether low abundant serum proteins differed based on age, sex, and fat mass in a healthy population of 94 males and 102 females from the MECHE cohort. The findings were replicated in 217 healthy male and 377 healthy female participants in the DiOGenes consortium. Of the 1129 proteins in the panel, 141, 51, and 112 proteins (adjusted p < 0.1) were identified in the MECHE cohort and significantly replicated in DiOGenes for sexual dimorphism, age, and fat mass, respectively. Pathway analysis classified a subset of proteins from the 3 phenotypes to the complement and coagulation cascades pathways and to immune and coagulation processes. These results demonstrated that specific proteins were statistically associated with dichotomous (male vs female) and continuous phenotypes (age, fat mass), which may influence the identification and use of biomarkers of clinical utility for health diagnosis and therapeutic strategies.

AB - Validated protein biomarkers are needed for assessing health trajectories, predicting and subclassifying disease, and optimizing diagnostic and therapeutic clinical decision-making. The sensitivity, specificity, accuracy, and precision of single or combinations of protein biomarkers may be altered by differences in physiological states limiting the ability to translate research results to clinically useful diagnostic tests. Aptamer based affinity assays were used to test whether low abundant serum proteins differed based on age, sex, and fat mass in a healthy population of 94 males and 102 females from the MECHE cohort. The findings were replicated in 217 healthy male and 377 healthy female participants in the DiOGenes consortium. Of the 1129 proteins in the panel, 141, 51, and 112 proteins (adjusted p < 0.1) were identified in the MECHE cohort and significantly replicated in DiOGenes for sexual dimorphism, age, and fat mass, respectively. Pathway analysis classified a subset of proteins from the 3 phenotypes to the complement and coagulation cascades pathways and to immune and coagulation processes. These results demonstrated that specific proteins were statistically associated with dichotomous (male vs female) and continuous phenotypes (age, fat mass), which may influence the identification and use of biomarkers of clinical utility for health diagnosis and therapeutic strategies.

KW - Journal Article

U2 - 10.1021/acs.jproteome.7b00501

DO - 10.1021/acs.jproteome.7b00501

M3 - Article

C2 - 28950061

VL - 16

SP - 4122

EP - 4133

JO - Journal of Proteome Research

JF - Journal of Proteome Research

SN - 1535-3893

IS - 11

ER -

Curran AM, Fogarty Draper C, Scott-Boyer M-P, Valsesia A, Roche HM, Ryan MF et al. Sexual Dimorphism, Age, and Fat Mass Are Key Phenotypic Drivers of Proteomic Signatures. Journal of Proteome Research. 2017 Nov 3;16(11):4122-4133. https://doi.org/10.1021/acs.jproteome.7b00501