title: A predictive computational framework for direct reprogramming between human cell types.
abstract: Transdifferentiation, the process of converting from one cell type to another without going through a pluripotent state, has great promise for regenerative medicine. The identification of key transcription factors for reprogramming is currently limited by the cost of exhaustive experimental testing of plausible sets of factors, an approach that is inefficient and unscalable. Here we present a predictive system (Mogrify) that combines gene expression data with regulatory network information to predict the reprogramming factors necessary to induce cell conversion. We have applied Mogrify to 173 human cell types and 134 tissues, defining an atlas of cellular reprogramming. Mogrify correctly predicts the transcription factors used in known transdifferentiations. Furthermore, we validated two new transdifferentiations predicted by Mogrify. We provide a practical and efficient mechanism for systematically implementing novel cell conversions, facilitating the generalization of reprogramming of human cells. Predictions are made available to help rapidly further the field of cell conversion.
authors.affiliation: Department of Computer Science, University of Bristol, Bristol, UK.|Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore.
authors.forename: Owen J L
authors.initials: OJ
authors.lastname: Rackham
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.|Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.|Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
authors.forename: Jaber
authors.initials: J
authors.lastname: Firas
authors.affiliation: Department of Computer Science, University of Bristol, Bristol, UK.
authors.forename: Hai
authors.initials: H
authors.lastname: Fang
authors.affiliation: Department of Computer Science, University of Bristol, Bristol, UK.
authors.forename: Matt E
authors.identifier: http://orcid.org/0000-0002-0001-3675
authors.initials: ME
authors.lastname: Oates
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.|Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.|Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Holmes
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.|Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
authors.forename: Anja S
authors.initials: AS
authors.lastname: Knaupp
authors.affiliation: RIKEN Omics Science Center, Yokohama, Japan (ceased to exist as of 1 April 2013 owing to reorganization).|Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan.
authors.forename: Harukazu
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.|Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.|Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Nefzger
authors.affiliation: RIKEN Omics Science Center, Yokohama, Japan (ceased to exist as of 1 April 2013 owing to reorganization).|Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan.|Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Carsten O
authors.initials: CO
authors.lastname: Daub
authors.affiliation: RIKEN Omics Science Center, Yokohama, Japan (ceased to exist as of 1 April 2013 owing to reorganization).|Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan.
authors.forename: Jay W
authors.initials: JW
authors.lastname: Shin
authors.affiliation: Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore.
authors.forename: Enrico
authors.initials: E
authors.lastname: Petretto
authors.affiliation: RIKEN Omics Science Center, Yokohama, Japan (ceased to exist as of 1 April 2013 owing to reorganization).|Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan.|Harry Perkins Institute of Medical Research, Queen Elizabeth II Medical Centre and Centre for Medical Research, University of Western Australia, Nedlands, Western Australia, Australia.
authors.forename: Alistair R R
authors.initials: AR
authors.lastname: Forrest
authors.affiliation: Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan.|RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.|Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia.|Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Polo
authors.affiliation: Department of Computer Science, University of Bristol, Bristol, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Gough
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D054338:Cell Transdifferentiation / Q000235:genetics*; D065150:Cellular Reprogramming / Q000235:genetics*; D005347:Fibroblasts; D053263:Gene Regulatory Networks; D006801:Humans; D057026:Induced Pluripotent Stem Cells; D044968:Regenerative Medicine; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
chemical_list: D014157:Transcription Factors