title: RiboAbacus: a model trained on polyribosome images predicts ribosome density and translational efficiency from mammalian transcriptomes.
abstract: Fluctuations in mRNA levels only partially contribute to determine variations in mRNA availability for translation, producing the well-known poor correlation between transcriptome and proteome data. Recent advances in microscopy now enable researchers to obtain high resolution images of ribosomes on transcripts, providing precious snapshots of translation in vivo. Here we propose RiboAbacus, a mathematical model that for the first time incorporates imaging data in a predictive model of transcript-specific ribosome densities and translational efficiencies. RiboAbacus uses a mechanistic model of ribosome dynamics, enabling the quantification of the relative importance of different features (such as codon usage and the 5' ramp effect) in determining the accuracy of predictions. The model has been optimized in the human Hek-293 cell line to fit thousands of images of human polysomes obtained by atomic force microscopy, from which we could get a reference distribution of the number of ribosomes per mRNA with unmatched resolution. After validation, we applied RiboAbacus to three case studies of known transcriptome-proteome datasets for estimating the translational efficiencies, resulting in an increased correlation with corresponding proteomes. RiboAbacus is an intuitive tool that allows an immediate estimation of crucial translation properties for entire transcriptomes, based on easily obtainable transcript expression levels.
authors.affiliation: Institute of Biophysics, CNR Unit at Trento, Via alla Cascata, 56/C-38123 Povo (TN), Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Lauria
authors.affiliation: Laboratory of Translational Genomics, Centre for Integrative Biology, Via delle Regole, 101-38123 Mattarello (TN), Italy.
authors.forename: Toma
authors.initials: T
authors.lastname: Tebaldi
authors.affiliation: Laboratory of Biomolecular Sequence and Structure Analysis for Health, Fondazione Bruno Kessler, Via Sommarive, 18-38123 Povo (TN), Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Lunelli
authors.affiliation: Laboratory of Translational Genomics, Centre for Integrative Biology, Via delle Regole, 101-38123 Mattarello (TN), Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Struffi
authors.affiliation: Laboratory of Translational Genomics, Centre for Integrative Biology, Via delle Regole, 101-38123 Mattarello (TN), Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Gatto
authors.affiliation: Mathematics Department, University of Trento, Via Sommarive, 14-38123 Povo (TN), Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pugliese
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via S. Giacomo, 14-40126 Bologna, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Brigotti
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via S. Giacomo, 14-40126 Bologna, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Montanaro
authors.affiliation: Laboratory of Transcriptional Networks, Centre for Integrative Biology, Via delle Regole, 101-38123 Mattarello (TN), Italy.
authors.forename: Yari
authors.initials: Y
authors.lastname: Ciribilli
authors.affiliation: Laboratory of Transcriptional Networks, Centre for Integrative Biology, Via delle Regole, 101-38123 Mattarello (TN), Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Inga
authors.affiliation: Laboratory of Translational Genomics, Centre for Integrative Biology, Via delle Regole, 101-38123 Mattarello (TN), Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Quattrone
authors.affiliation: School of Informatics, University of Edinburgh, 10 Crichton Street, Edinburgh, Midlothian EH8 9AB, UK.
authors.forename: Guido
authors.initials: G
authors.lastname: Sanguinetti
authors.affiliation: Institute of Biophysics, CNR Unit at Trento, Via alla Cascata, 56/C-38123 Povo (TN), Italy gabriella.viero@cnr.it.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Viero
mesh_terms: D000818:Animals; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D018625:Microscopy, Atomic Force; D008954:Models, Biological; D011132:Polyribosomes / Q000648:ultrastructure*; D014176:Protein Biosynthesis; D040901:Proteomics; D011817:Rabbits; D012156:Reticulocytes / Q000648:ultrastructure; D012270:Ribosomes / Q000648:ultrastructure; D012984:Software; D059467:Transcriptome