A systems biology approach using metabolomic data reveals genes and pathways interacting to modulate divergent growth in cattle

Philipp Widmann, Antonio Reverter, Marina R.S. Fortes, Rosemarie Weikard, Karsten Suhre, Harald Hammon, Elke Albrecht, Christa Kuehn

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background: Systems biology enables the identification of gene networks that modulate complex traits. Comprehensive metabolomic analyses provide innovative phenotypes that are intermediate between the initiator of genetic variability, the genome, and raw phenotypes that are influenced by a large number of environmental effects. The present study combines two concepts, systems biology and metabolic analyses, in an approach without prior functional hypothesis in order to dissect genes and molecular pathways that modulate differential growth at the onset of puberty in male cattle. Furthermore, this integrative strategy was applied to specifically explore distinctive gene interactions of non-SMC condensin I complex, subunit G (NCAPG) and myostatin (GDF8), known modulators of pre- and postnatal growth that are only partially understood for their molecular pathways affecting differential body weight. Results: Our study successfully established gene networks and interacting partners affecting growth at the onset of puberty in cattle. We demonstrated the biological relevance of the created networks by comparison to randomly created networks. Our data showed that GnRH (Gonadotropin-releasing hormone) signaling is associated with divergent growth at the onset of puberty and revealed two highly connected hubs, BTC and DGKH, within the network. Both genes are known to directly interact with the GnRH signaling pathway. Furthermore, a gene interaction network for NCAPG containing 14 densely connected genes revealed novel information concerning the functional role of NCAPG in divergent growth. Conclusions: Merging both concepts, systems biology and metabolomic analyses, successfully yielded new insights into gene networks and interacting partners affecting growth at the onset of puberty in cattle. Genetic modulation in GnRH signaling was identified as key modifier of differential cattle growth at the onset of puberty. In addition, the benefit of our innovative concept without prior functional hypothesis was demonstrated by data suggesting that NCAPG might contribute to vascular smooth muscle contraction by indirect effects on the NO pathway via modulation of arginine metabolism. Our study shows for the first time in cattle that integration of genetic, physiological and metabolomics data in a systems biology approach will enable (or contribute to) an improved understanding of metabolic and gene networks and genotype-phenotype relationships.

Original languageEnglish
Article number798
JournalBMC Genomics
Volume14
Issue number1
DOIs
Publication statusPublished - 18 Nov 2013

Fingerprint

Metabolomics
Systems Biology
Gene Regulatory Networks
Puberty
Growth
Genes
Gonadotropin-Releasing Hormone
Phenotype
Myostatin
Muscle Contraction
Metabolic Networks and Pathways
Vascular Smooth Muscle
Arginine
Genotype
Body Weight
Genome

Keywords

  • Cattle
  • Divergent growth
  • Genome-wide association study
  • Metabolomics
  • Puberty
  • SEGFAM
  • Systems biology

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

A systems biology approach using metabolomic data reveals genes and pathways interacting to modulate divergent growth in cattle. / Widmann, Philipp; Reverter, Antonio; Fortes, Marina R.S.; Weikard, Rosemarie; Suhre, Karsten; Hammon, Harald; Albrecht, Elke; Kuehn, Christa.

In: BMC Genomics, Vol. 14, No. 1, 798, 18.11.2013.

Research output: Contribution to journalArticle

Widmann, Philipp ; Reverter, Antonio ; Fortes, Marina R.S. ; Weikard, Rosemarie ; Suhre, Karsten ; Hammon, Harald ; Albrecht, Elke ; Kuehn, Christa. / A systems biology approach using metabolomic data reveals genes and pathways interacting to modulate divergent growth in cattle. In: BMC Genomics. 2013 ; Vol. 14, No. 1.
@article{d3e1d35ad481447da60f1c5e933a5efa,
title = "A systems biology approach using metabolomic data reveals genes and pathways interacting to modulate divergent growth in cattle",
abstract = "Background: Systems biology enables the identification of gene networks that modulate complex traits. Comprehensive metabolomic analyses provide innovative phenotypes that are intermediate between the initiator of genetic variability, the genome, and raw phenotypes that are influenced by a large number of environmental effects. The present study combines two concepts, systems biology and metabolic analyses, in an approach without prior functional hypothesis in order to dissect genes and molecular pathways that modulate differential growth at the onset of puberty in male cattle. Furthermore, this integrative strategy was applied to specifically explore distinctive gene interactions of non-SMC condensin I complex, subunit G (NCAPG) and myostatin (GDF8), known modulators of pre- and postnatal growth that are only partially understood for their molecular pathways affecting differential body weight. Results: Our study successfully established gene networks and interacting partners affecting growth at the onset of puberty in cattle. We demonstrated the biological relevance of the created networks by comparison to randomly created networks. Our data showed that GnRH (Gonadotropin-releasing hormone) signaling is associated with divergent growth at the onset of puberty and revealed two highly connected hubs, BTC and DGKH, within the network. Both genes are known to directly interact with the GnRH signaling pathway. Furthermore, a gene interaction network for NCAPG containing 14 densely connected genes revealed novel information concerning the functional role of NCAPG in divergent growth. Conclusions: Merging both concepts, systems biology and metabolomic analyses, successfully yielded new insights into gene networks and interacting partners affecting growth at the onset of puberty in cattle. Genetic modulation in GnRH signaling was identified as key modifier of differential cattle growth at the onset of puberty. In addition, the benefit of our innovative concept without prior functional hypothesis was demonstrated by data suggesting that NCAPG might contribute to vascular smooth muscle contraction by indirect effects on the NO pathway via modulation of arginine metabolism. Our study shows for the first time in cattle that integration of genetic, physiological and metabolomics data in a systems biology approach will enable (or contribute to) an improved understanding of metabolic and gene networks and genotype-phenotype relationships.",
keywords = "Cattle, Divergent growth, Genome-wide association study, Metabolomics, Puberty, SEGFAM, Systems biology",
author = "Philipp Widmann and Antonio Reverter and Fortes, {Marina R.S.} and Rosemarie Weikard and Karsten Suhre and Harald Hammon and Elke Albrecht and Christa Kuehn",
year = "2013",
month = "11",
day = "18",
doi = "10.1186/1471-2164-14-798",
language = "English",
volume = "14",
journal = "BMC Genomics",
issn = "1471-2164",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - A systems biology approach using metabolomic data reveals genes and pathways interacting to modulate divergent growth in cattle

AU - Widmann, Philipp

AU - Reverter, Antonio

AU - Fortes, Marina R.S.

AU - Weikard, Rosemarie

AU - Suhre, Karsten

AU - Hammon, Harald

AU - Albrecht, Elke

AU - Kuehn, Christa

PY - 2013/11/18

Y1 - 2013/11/18

N2 - Background: Systems biology enables the identification of gene networks that modulate complex traits. Comprehensive metabolomic analyses provide innovative phenotypes that are intermediate between the initiator of genetic variability, the genome, and raw phenotypes that are influenced by a large number of environmental effects. The present study combines two concepts, systems biology and metabolic analyses, in an approach without prior functional hypothesis in order to dissect genes and molecular pathways that modulate differential growth at the onset of puberty in male cattle. Furthermore, this integrative strategy was applied to specifically explore distinctive gene interactions of non-SMC condensin I complex, subunit G (NCAPG) and myostatin (GDF8), known modulators of pre- and postnatal growth that are only partially understood for their molecular pathways affecting differential body weight. Results: Our study successfully established gene networks and interacting partners affecting growth at the onset of puberty in cattle. We demonstrated the biological relevance of the created networks by comparison to randomly created networks. Our data showed that GnRH (Gonadotropin-releasing hormone) signaling is associated with divergent growth at the onset of puberty and revealed two highly connected hubs, BTC and DGKH, within the network. Both genes are known to directly interact with the GnRH signaling pathway. Furthermore, a gene interaction network for NCAPG containing 14 densely connected genes revealed novel information concerning the functional role of NCAPG in divergent growth. Conclusions: Merging both concepts, systems biology and metabolomic analyses, successfully yielded new insights into gene networks and interacting partners affecting growth at the onset of puberty in cattle. Genetic modulation in GnRH signaling was identified as key modifier of differential cattle growth at the onset of puberty. In addition, the benefit of our innovative concept without prior functional hypothesis was demonstrated by data suggesting that NCAPG might contribute to vascular smooth muscle contraction by indirect effects on the NO pathway via modulation of arginine metabolism. Our study shows for the first time in cattle that integration of genetic, physiological and metabolomics data in a systems biology approach will enable (or contribute to) an improved understanding of metabolic and gene networks and genotype-phenotype relationships.

AB - Background: Systems biology enables the identification of gene networks that modulate complex traits. Comprehensive metabolomic analyses provide innovative phenotypes that are intermediate between the initiator of genetic variability, the genome, and raw phenotypes that are influenced by a large number of environmental effects. The present study combines two concepts, systems biology and metabolic analyses, in an approach without prior functional hypothesis in order to dissect genes and molecular pathways that modulate differential growth at the onset of puberty in male cattle. Furthermore, this integrative strategy was applied to specifically explore distinctive gene interactions of non-SMC condensin I complex, subunit G (NCAPG) and myostatin (GDF8), known modulators of pre- and postnatal growth that are only partially understood for their molecular pathways affecting differential body weight. Results: Our study successfully established gene networks and interacting partners affecting growth at the onset of puberty in cattle. We demonstrated the biological relevance of the created networks by comparison to randomly created networks. Our data showed that GnRH (Gonadotropin-releasing hormone) signaling is associated with divergent growth at the onset of puberty and revealed two highly connected hubs, BTC and DGKH, within the network. Both genes are known to directly interact with the GnRH signaling pathway. Furthermore, a gene interaction network for NCAPG containing 14 densely connected genes revealed novel information concerning the functional role of NCAPG in divergent growth. Conclusions: Merging both concepts, systems biology and metabolomic analyses, successfully yielded new insights into gene networks and interacting partners affecting growth at the onset of puberty in cattle. Genetic modulation in GnRH signaling was identified as key modifier of differential cattle growth at the onset of puberty. In addition, the benefit of our innovative concept without prior functional hypothesis was demonstrated by data suggesting that NCAPG might contribute to vascular smooth muscle contraction by indirect effects on the NO pathway via modulation of arginine metabolism. Our study shows for the first time in cattle that integration of genetic, physiological and metabolomics data in a systems biology approach will enable (or contribute to) an improved understanding of metabolic and gene networks and genotype-phenotype relationships.

KW - Cattle

KW - Divergent growth

KW - Genome-wide association study

KW - Metabolomics

KW - Puberty

KW - SEGFAM

KW - Systems biology

UR - http://www.scopus.com/inward/record.url?scp=84887781463&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84887781463&partnerID=8YFLogxK

U2 - 10.1186/1471-2164-14-798

DO - 10.1186/1471-2164-14-798

M3 - Article

C2 - 24246134

AN - SCOPUS:84887781463

VL - 14

JO - BMC Genomics

JF - BMC Genomics

SN - 1471-2164

IS - 1

M1 - 798

ER -