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High-dimensional imaging using combinatorial channel multiplexing and deep learning

delete2025-03-25
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PRE
AI
R
Raz Ben-Uri
L
Lior Ben Shabat
D
Dana Shainshein
O
Omer Bar-Tal
Y
Yuval Bussi
N
Noa Maimon
T
Tal Keidar Haran
I
Idan Milo
I
Inna Goliand
Y
Yoseph Addadi
T
Tomer‐Meir Salame
A
Alexander Rochwarger
C
Christian M. Schürch
S
Shai Bagon
O
Ofer Elhanani
L
Leeat Keren *
DOI:10.1038/s41587-025-02585-0delete
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Abstract

Abstract

En 中文
Understanding tissue structure and function requires tools that quantify the expression of multiple proteins at single-cell resolution while preserving spatial information. Current imaging technologies use a separate channel for each protein, limiting throughput and scalability. Here, we present combinatorial multiplexing (CombPlex), a combinatorial staining platform coupled with an algorithmic framework to exponentially increase the number of measured proteins. Every protein can be imaged in several channels and every channel contains agglomerated images of several proteins. These combinatorically compressed images are then decompressed to individual protein images using deep learning. We achieve accurate reconstruction when compressing the stains of 22 proteins to five imaging channels. We demonstrate the approach both in fluorescence microscopy and in mass-based imaging and show successful application across multiple tissues and cancer types. CombPlex can escalate the number of proteins measured by any imaging modality, without the need for specialized instrumentation.
Keywords:
IMMUNOHISTOCHEMISTRY
CELLS

Journal

Nature Biotechnology cover
Nature Biotechnology
IF:
41.7
Papers:
1.2W
Citations:
10.1W

Organization

W
Weizmann Inst Sci
Scholars:
753
Papers: 280
Citations: 161
C
comprehens canc ctr tubingen
Scholars:
2
Papers: 2
Citations: 1