title: Simple, Scalable Proteomic Imaging for High-Dimensional Profiling of Intact Systems.
abstract: Combined measurement of diverse molecular and anatomical traits that span multiple levels remains a major challenge in biology. Here, we introduce a simple method that enables proteomic imaging for scalable, integrated, high-dimensional phenotyping of both animal tissues and human clinical samples. This method, termed SWITCH, uniformly secures tissue architecture, native biomolecules, and antigenicity across an entire system by synchronizing the tissue preservation reaction. The heat- and chemical-resistant nature of the resulting framework permits multiple rounds (>20) of relabeling. We have performed 22 rounds of labeling of a single tissue with precise co-registration of multiple datasets. Furthermore, SWITCH synchronizes labeling reactions to improve probe penetration depth and uniformity of staining. With SWITCH, we performed combinatorial protein expression profiling of the human cortex and also interrogated the geometric structure of the fiber pathways in mouse brains. Such integrated high-dimensional information may accelerate our understanding of biological systems at multiple levels.
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Evan
authors.initials: E
authors.lastname: Murray
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Jae Hun
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Simons Center for Data Analysis, 160 Fifth Avenue, 8th Floor, New York, NY 10010, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Goodwin
authors.affiliation: Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Taeyun
authors.initials: T
authors.lastname: Ku
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Swaney
authors.affiliation: Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Sung-Yon
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Heejin
authors.initials: H
authors.lastname: Choi
authors.affiliation: Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Young-Gyun
authors.initials: YG
authors.lastname: Park
authors.affiliation: Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Jeong-Yoon
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Austin
authors.initials: A
authors.lastname: Hubbert
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: McCue
authors.affiliation: Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Vassallo
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Naveed
authors.initials: N
authors.lastname: Bakh
authors.affiliation: C.S. Kubik Laboratory of Neuropathology, Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Frosch
authors.affiliation: Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Van J
authors.initials: VJ
authors.lastname: Wedeen
authors.affiliation: Simons Center for Data Analysis, 160 Fifth Avenue, 8th Floor, New York, NY 10010, USA; Princeton Neuroscience Institute and Computer Science Department, Princeton University, Princeton, NJ 08544, USA.
authors.forename: H Sebastian
authors.initials: HS
authors.lastname: Seung
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02142, USA. Electronic address: khchung@mit.edu.
authors.forename: Kwanghun
authors.initials: K
authors.lastname: Chung
mesh_terms: D000465:Algorithms; D000818:Animals; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D057054:Molecular Imaging / Q000379:methods*; D009413:Nerve Fibers, Myelinated / Q000737:chemistry; D040901:Proteomics; D019163:Reducing Agents; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014021:Tissue Preservation / Q000379:methods*
chemical_list: D019163:Reducing Agents