title: New insights into functional regulation in MS-based drug profiling.
abstract: We present a novel data analysis strategy which combined with subcellular fractionation and liquid chromatography-mass spectrometry (LC-MS) based proteomics provides a simple and effective workflow for global drug profiling. Five subcellular fractions were obtained by differential centrifugation followed by high resolution LC-MS and complete functional regulation analysis. The methodology combines functional regulation and enrichment analysis into a single visual summary. The workflow enables improved insight into perturbations caused by drugs. We provide a statistical argument to demonstrate that even crude subcellular fractions leads to improved functional characterization. We demonstrate this data analysis strategy on data obtained in a MS-based global drug profiling study. However, this strategy can also be performed on other types of large scale biological data.
authors.affiliation: Computational and Experimental Biology Group, National Health Institute Dr. Ricardo Jorge, IP, Av. Padre Cruz, 1649-016, Lisbon, Portugal.
authors.forename: Ana Sofia
authors.initials: AS
authors.lastname: Carvalho
authors.affiliation: Proteomics Resource Center, The Rockefeller University, 1230 York Avenue, New York, New York 10065-6399.
authors.forename: Henrik
authors.initials: H
authors.lastname: Molina
authors.affiliation: Computational and Experimental Biology Group, National Health Institute Dr. Ricardo Jorge, IP, Av. Padre Cruz, 1649-016, Lisbon, Portugal.
authors.forename: Rune
authors.initials: R
authors.lastname: Matthiesen
mesh_terms: D002458:Cell Fractionation; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism; D015507:Drugs, Investigational / Q000494:pharmacology*; D015870:Gene Expression; D020869:Gene Expression Profiling; D057166:High-Throughput Screening Assays; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods*; D008861:Microsomes / Q000187:drug effects* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D058977:Molecular Sequence Annotation; D020543:Proteome / Q000819:agonists / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000235:genetics; D040901:Proteomics / Q000379:methods
chemical_list: D015507:Drugs, Investigational; D020543:Proteome