title: Platform for combined analysis of functional and biomolecular phenotypes of the same cell.
abstract: Functional and molecular cell-to-cell variability is pivotal at the cellular, tissue and whole-organism levels. Yet, the ultimate goal of directly correlating the function of the individual cell with its biomolecular profile remains elusive. We present a platform for integrated analysis of functional and transcriptional phenotypes in the same single cells. We investigated changes in the cellular respiration and gene expression diversity resulting from adaptation to repeated episodes of acute hypoxia in a premalignant progression model. We find differential, progression stage-specific alterations in phenotypic heterogeneity and identify cells with aberrant phenotypes. To our knowledge, this study is the first demonstration of an integrated approach to elucidate how heterogeneity at the transcriptional level manifests in the physiologic profile of individual cells in the context of disease progression.
authors.affiliation: Center for Biosignatures Discovery Automation, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
authors.forename: L
authors.initials: L
authors.lastname: Kelbauskas
authors.affiliation: Center for Biosignatures Discovery Automation, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ashili
authors.affiliation: Center for Biosignatures Discovery Automation, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Center for Biosignatures Discovery Automation, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
authors.forename: A
authors.initials: A
authors.lastname: Rezaie
authors.affiliation: Center for Biosignatures Discovery Automation, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
authors.forename: K
authors.initials: K
authors.lastname: Lee
authors.affiliation: Center for Biosignatures Discovery Automation, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
authors.forename: D
authors.initials: D
authors.lastname: Derkach
authors.affiliation: Center for Biosignatures Discovery Automation, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
authors.forename: B
authors.initials: B
authors.lastname: Ueberroth
authors.affiliation: Center for Biosignatures Discovery Automation, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
authors.forename: W
authors.initials: W
authors.lastname: Gao
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Paulson
authors.affiliation: Center for Biosignatures Discovery Automation, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Center for Biosignatures Discovery Automation, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Center for Biosignatures Discovery Automation, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
authors.forename: D
authors.initials: D
authors.lastname: Smith
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Reid
authors.affiliation: Center for Biosignatures Discovery Automation, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
authors.forename: Deirdre R
authors.initials: DR
authors.lastname: Meldrum
mesh_terms: D019069:Cell Respiration / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D058977:Molecular Sequence Annotation; D010101:Oxygen Consumption; D010641:Phenotype; D025341:Principal Component Analysis; D059010:Single-Cell Analysis / Q000379:methods*