title: Systems view of adipogenesis via novel omics-driven and tissue-specific activity scoring of network functional modules.
abstract: The investigation of the complex processes involved in cellular differentiation must be based on unbiased, high throughput data processing methods to identify relevant biological pathways. A number of bioinformatics tools are available that can generate lists of pathways ranked by statistical significance (i.e. by p-value), while ideally it would be desirable to functionally score the pathways relative to each other or to other interacting parts of the system or process. We describe a new computational method (Network Activity Score Finder - NASFinder) to identify tissue-specific, omics-determined sub-networks and the connections with their upstream regulator receptors to obtain a systems view of the differentiation of human adipocytes. Adipogenesis of human SBGS pre-adipocyte cells in vitro was monitored with a transcriptomic data set comprising six time points (0, 6, 48, 96, 192, 384 hours). To elucidate the mechanisms of adipogenesis, NASFinder was used to perform time-point analysis by comparing each time point against the control (0 h) and time-lapse analysis by comparing each time point with the previous one. NASFinder identified the coordinated activity of seemingly unrelated processes between each comparison, providing the first systems view of adipogenesis in culture. NASFinder has been implemented into a web-based, freely available resource associated with novel, easy to read visualization of omics data sets and network modules.
authors.affiliation: The Microsoft Research - University of Trento Centre for Computational and Systems Biology, Piazza Manifattura 1, 38068 Rovereto, Italy.
authors.forename: Isar
authors.initials: I
authors.lastname: Nassiri
authors.affiliation: The Microsoft Research - University of Trento Centre for Computational and Systems Biology, Piazza Manifattura 1, 38068 Rovereto, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Lombardo
authors.affiliation: The Microsoft Research - University of Trento Centre for Computational and Systems Biology, Piazza Manifattura 1, 38068 Rovereto, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Lauria
authors.affiliation: The Microsoft Research - University of Trento Centre for Computational and Systems Biology, Piazza Manifattura 1, 38068 Rovereto, Italy.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Morine
authors.affiliation: The Microsoft Research - University of Trento Centre for Computational and Systems Biology, Piazza Manifattura 1, 38068 Rovereto, Italy.
authors.forename: Petros
authors.initials: P
authors.lastname: Moyseos
authors.affiliation: Division of Systems Biology, National Center for Toxicological Research, FDA, 3900 NCTR Road, Jefferson, AR 72079, USA.
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Varma
authors.affiliation: Division of Systems Biology, National Center for Toxicological Research, FDA, 3900 NCTR Road, Jefferson, AR 72079, USA.
authors.forename: Greg T
authors.initials: GT
authors.lastname: Nolen
authors.affiliation: Division of Systems Biology, National Center for Toxicological Research, FDA, 3900 NCTR Road, Jefferson, AR 72079, USA.
authors.forename: Bridgett
authors.initials: B
authors.lastname: Knox
authors.affiliation: Division of Systems Biology, National Center for Toxicological Research, FDA, 3900 NCTR Road, Jefferson, AR 72079, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sloper
authors.affiliation: Nestlé Institute of Health Science, Lausanne, Switzerland.
authors.forename: Jim
authors.initials: J
authors.lastname: Kaput
authors.affiliation: The Microsoft Research - University of Trento Centre for Computational and Systems Biology, Piazza Manifattura 1, 38068 Rovereto, Italy.|Department of Mathematics, University of Trento, Via Sommarive 14, 38050 Povo, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Priami
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D050156:Adipogenesis; D002454:Cell Differentiation; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D005786:Gene Expression Regulation; D006801:Humans; D020407:Internet; D049490:Systems Biology; D013997:Time Factors; D059467:Transcriptome