title: A Novel Systems-Biology Algorithm for the Analysis of Coordinated Protein Responses Using Quantitative Proteomics.
abstract: The coordinated behavior of proteins is central to systems biology. However, the underlying mechanisms are poorly known and methods to analyze coordination by conventional quantitative proteomics are still lacking. We present the Systems Biology Triangle (SBT), a new algorithm that allows the study of protein coordination by pairwise quantitative proteomics. The Systems Biology Triangle detected statistically significant coordination in diverse biological models of very different nature and subjected to different kinds of perturbations. The Systems Biology Triangle also revealed with unprecedented molecular detail an array of coordinated, early protein responses in vascular smooth muscle cells treated at different times with angiotensin-II. These responses included activation of protein synthesis, folding, turnover, and muscle contraction - consistent with a differentiated phenotype-as well as the induction of migration and the repression of cell proliferation and secretion. Remarkably, the majority of the altered functional categories were protein complexes, interaction networks, or metabolic pathways. These changes could not be detected by other algorithms widely used by the proteomics community, and the vast majority of proteins involved have not been described before to be regulated by AngII. The unique capabilities of The Systems Biology Triangle to detect functional protein alterations produced by the coordinated action of proteins in pairwise quantitative proteomics experiments make this algorithm an attractive choice for the biological interpretation of results on a routine basis.
authors.affiliation: From the ‡Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Fernando
authors.identifier: 0000-0002-2105-2905
authors.initials: F
authors.lastname: García-Marqués
authors.affiliation: From the ‡Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Marco
authors.identifier: 0000-0002-7129-0602
authors.initials: M
authors.lastname: Trevisan-Herraz
authors.affiliation: From the ‡Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Martínez-Martínez
authors.affiliation: From the ‡Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Camafeita
authors.affiliation: From the ‡Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Jorge
authors.affiliation: From the ‡Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Lopez
authors.affiliation: From the ‡Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Nerea
authors.initials: N
authors.lastname: Méndez-Barbero
authors.affiliation: From the ‡Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Simón
authors.identifier: 0000-0002-9805-9988
authors.initials: S
authors.lastname: Méndez-Ferrer
authors.affiliation: From the ‡Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Miguel Angel
authors.identifier: 0000-0001-9077-391X
authors.initials: MA
authors.lastname: Del Pozo
authors.affiliation: From the ‡Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Borja
authors.initials: B
authors.lastname: Ibáñez
authors.affiliation: From the ‡Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Vicente
authors.identifier: 0000-0002-0125-7209
authors.initials: V
authors.lastname: Andrés
authors.affiliation: From the ‡Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Francisco
authors.identifier: 0000-0002-2656-1290
authors.initials: F
authors.lastname: Sánchez-Madrid
authors.affiliation: From the ‡Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
authors.forename: Juan Miguel
authors.identifier: 0000-0001-5779-9122
authors.initials: JM
authors.lastname: Redondo
authors.affiliation: From the ‡Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain ebonzon@cnic.es jvazquez@cnic.es.
authors.forename: Elena
authors.initials: E
authors.lastname: Bonzon-Kulichenko
authors.affiliation: From the ‡Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain ebonzon@cnic.es jvazquez@cnic.es.
authors.forename: Jesús
authors.initials: J
authors.lastname: Vázquez
mesh_terms: D000465:Algorithms; D000818:Animals; D057166:High-Throughput Screening Assays; D006801:Humans; D060066:Protein Interaction Maps; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D049490:Systems Biology / Q000379:methods*
chemical_list: D020543:Proteome