Simple, Scalable Proteomic Imaging for High-Dimensional Profiling of Intact Systems
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....
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2017
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| Online Access: | http://hdl.handle.net/1721.1/107624 https://orcid.org/0000-0003-2927-7321 https://orcid.org/0000-0003-2880-349X https://orcid.org/0000-0001-9447-7579 https://orcid.org/0000-0002-4830-9133 https://orcid.org/0000-0003-3681-7410 https://orcid.org/0000-0001-6376-1323 https://orcid.org/0000-0002-2287-9998 https://orcid.org/0000-0002-0907-6736 https://orcid.org/0000-0002-8167-3340 |
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| author | Frosch, Matthew P. Wedeen, Van J. Seung, H. Sebastian Murray, Evan Cho, Jae Hun Ku, Taeyun Swaney, Justin Mark Kim, Sung-Yon Choi, Heejin Park, Young-Gyun Park, Jeong-Yoon Hubbert, Austin W. McCue, Margaret Grace Ling, Sara Lynn Bakh, Naveed Ali Chung, Kwanghun |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Frosch, Matthew P. Wedeen, Van J. Seung, H. Sebastian Murray, Evan Cho, Jae Hun Ku, Taeyun Swaney, Justin Mark Kim, Sung-Yon Choi, Heejin Park, Young-Gyun Park, Jeong-Yoon Hubbert, Austin W. McCue, Margaret Grace Ling, Sara Lynn Bakh, Naveed Ali Chung, Kwanghun |
| author_sort | Frosch, Matthew P. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:07:33Z |
| format | Article |
| id | mit-1721.1/107624 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:07:33Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1076242022-09-29T12:52:50Z Simple, Scalable Proteomic Imaging for High-Dimensional Profiling of Intact Systems Frosch, Matthew P. Wedeen, Van J. Seung, H. Sebastian Murray, Evan Cho, Jae Hun Ku, Taeyun Swaney, Justin Mark Kim, Sung-Yon Choi, Heejin Park, Young-Gyun Park, Jeong-Yoon Hubbert, Austin W. McCue, Margaret Grace Ling, Sara Lynn Bakh, Naveed Ali Chung, Kwanghun Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Massachusetts Institute of Technology. Department of Chemical Engineering Picower Institute for Learning and Memory Murray, Evan Cho, Jae Hun Ku, Taeyun Swaney, Justin Mark Kim, Sung-Yon Choi, Heejin Park, Young-Gyun Park, Jeong-Yoon Hubbert, Austin W. McCue, Margaret Grace Ling, Sara Lynn Bakh, Naveed Ali Chung, Kwanghun 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. Simons Foundation. Postdoctoral Fellowship Life Sciences Research Foundation Burroughs Wellcome Fund (Career Award at the Scientific Interface) Searle Scholars Program Michael J. Fox Foundation for Parkinson's Research United States. Defense Advanced Research Projects Agency National Institutes of Health (U.S.) (1-U01-NS090473-01) 2017-03-21T19:45:57Z 2017-03-21T19:45:57Z 2015-12 2015-10 Article http://purl.org/eprint/type/JournalArticle 0092-8674 1097-4172 http://hdl.handle.net/1721.1/107624 Murray, Evan et al. “Simple, Scalable Proteomic Imaging for High-Dimensional Profiling of Intact Systems.” Cell 163.6 (2015): 1500–1514. https://orcid.org/0000-0003-2927-7321 https://orcid.org/0000-0003-2880-349X https://orcid.org/0000-0001-9447-7579 https://orcid.org/0000-0002-4830-9133 https://orcid.org/0000-0003-3681-7410 https://orcid.org/0000-0001-6376-1323 https://orcid.org/0000-0002-2287-9998 https://orcid.org/0000-0002-0907-6736 https://orcid.org/0000-0002-8167-3340 en_US http://dx.doi.org/10.1016/j.cell.2015.11.025 Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Frosch, Matthew P. Wedeen, Van J. Seung, H. Sebastian Murray, Evan Cho, Jae Hun Ku, Taeyun Swaney, Justin Mark Kim, Sung-Yon Choi, Heejin Park, Young-Gyun Park, Jeong-Yoon Hubbert, Austin W. McCue, Margaret Grace Ling, Sara Lynn Bakh, Naveed Ali Chung, Kwanghun Simple, Scalable Proteomic Imaging for High-Dimensional Profiling of Intact Systems |
| title | Simple, Scalable Proteomic Imaging for High-Dimensional Profiling of Intact Systems |
| title_full | Simple, Scalable Proteomic Imaging for High-Dimensional Profiling of Intact Systems |
| title_fullStr | Simple, Scalable Proteomic Imaging for High-Dimensional Profiling of Intact Systems |
| title_full_unstemmed | Simple, Scalable Proteomic Imaging for High-Dimensional Profiling of Intact Systems |
| title_short | Simple, Scalable Proteomic Imaging for High-Dimensional Profiling of Intact Systems |
| title_sort | simple scalable proteomic imaging for high dimensional profiling of intact systems |
| url | http://hdl.handle.net/1721.1/107624 https://orcid.org/0000-0003-2927-7321 https://orcid.org/0000-0003-2880-349X https://orcid.org/0000-0001-9447-7579 https://orcid.org/0000-0002-4830-9133 https://orcid.org/0000-0003-3681-7410 https://orcid.org/0000-0001-6376-1323 https://orcid.org/0000-0002-2287-9998 https://orcid.org/0000-0002-0907-6736 https://orcid.org/0000-0002-8167-3340 |
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