Editorial

https://doi.org/10.1038/s41592-024-02565-3

Method of the Year 2024: spatial proteomics

Approaches for profiling the spatial field of spatial proteomics. The piece further
proteome in tissues are the basis describes how generating large atlases will
of atlas-scale projects that are help reveal the intricacies of complex tissues
and pave the way for precision medicine. It
delivering on their promise for
ends with a discussion of technological devel-
understanding biological complexity
opments that will help move the field forward,
in health and disease. briefly commenting on the role artificial intel-

H
ligence may play in the future.
umans by nature are inquisitive. Computational tools for spatial proteomics
We love to explore, and as we do, are the focus of the second Comment, from
we make maps. Perhaps it is then Yuval Bussi and Leeat Keren5. These authors
not surprising that we find our- note that current image processing and analy-
selves in an age of atlas-building sis workflow are well defined but fragmented,
as we explore the incredible complexity of with various steps happening back to back
biological systems with cutting-edge meth- rather than in an integrated fashion. They
ods to better understand how cells, tissues, envision a future for the field where image
organs and organisms connect structure processing and analysis steps work in concert
and function. for improved biological discovery.
In the spirit of exploring and mapping bio- The third Comment6, from Daniela Quail
logical complexity, we have chosen spatial and Logan Walsh, discusses how spatial pro-
proteomics as our Method of the Year for teomics has revolutionized cancer research,
its critical role in revealing the organization development of DVP and other methods seek- from our understanding of tissue organiza-
of complex tissues. Spatial proteomics is ing new ways to explore the spatial proteome tion and cell–cell interactions to how it has
an umbrella term that covers a broad swath in greater depth and breadth. In addition, we shaped our thinking on how the immune
of immunohistochemistry-based methods were inspired by the current efforts of large system interacts with tumors. The piece
including, but not limited to, cyclic immuno- consortia such as the Human BioMolecular also covers the potential role of spatial pro-
fluorescence (cycIF), co-detection by indexing Atlas Program (HuBMAP) and the Human teomics in combination with artificial intel-
(CODEX), iterative bleaching extends multi- Tumor Atlas Network (HTAN) not only to cre- ligence in generating hypotheses for basic

CREDIT: ELHAM KARIMI AND SIMON MILETTE, WALSH AND QUAIL LABS, ROSALIND AND MORRIS GOODMAN CANCER INSTITUTE
plexity (IBEX), multiplexed ion beam imaging ate large atlases of data for the scientific and research, improving personalized medicine,
(MIBI) and imaging mass cytometry (IMC). medical communities, but also to develop and guiding future therapeutic strategies to
These approaches can be used to generate tools to process, analyze, visualize and mine fight cancer.
highly multiplexed images of specimens such the data to go beyond the pretty pictures and The fourth Comment, from Thierry Nor-
as tissue and organ slices to understand their deeper into biological discovery. This month’s dmann, Andreas Mund and Matthias Mann7,
protein composition and spatial organization issue features two papers from the HTAN introduces deep visual proteomics and the
and are the basis of many global atlas projects. consortium: an Article from Peter Sorger and benefits of using mass spectrometry to probe
We are also excited about a newer technique colleagues1 describing CyLinter, an improved the complexity of the proteome during pro-
known as deep visual proteomics (DVP), in tool for quality control of highly multiplexed cesses such as development or in disease. They
which complex samples are laser dissected images, and an Article from Benjamin Raphael note that future improvements to sensitivity
and individual dissociated cells are analyzed and colleagues2 presenting CalicoST, an algo- will allow mass spectrometry access to the
by mass spectrometry in such a way that their rithm to simultaneously infer allele-specific entire proteome, including post-translational
spatial context information is retained to copy number aberrations and reconstruct spa- modifications, with single-cell resolution.
create spatial protein maps. A major benefit tial tumor evolution from spatially resolved They also discuss the benefits of combining
of this technique is that it is not limited by transcriptomics data. For this month’s News DVP with other ’omics methods, future efforts
the number of available antibodies and thus Feature, journalist Vivien Marx asked some to democratize the technology, and moving
achieves substantially greater proteome researchers about atlas-building and where the technology into the clinic.
coverage. they see things going next3. Is spatial proteomics enough? The final
Spatial proteomics technologies such Our special issue features a series of Com- Comment, from Rong Fan8, discusses spatial
as immunofluorescence have been around ments on the past, present and future of spa- proteomics in the context of other ’omics
longer than other spatial biology methods, tial proteomics. The first piece4, from Bernd technologies and the importance of inte-
such as spatially resolved transcriptomics, Bodenmiller, introduces why proteins are grating complementary technologies such
which was our Method of the Year in 2021, so such interesting targets for biological inves- as spatial transcriptomics and spatial epige-
why are we choosing it as Method of the Year tigations and offers a brief look back at how netic profiling to gain a more holistic under-
now? For one, we were excited by the recent immunofluorescence has grown into the standing of biological complexity. This piece

nature methods Volume 21 | December 2024 | 2195–2196 | 2195

discusses the history of spatial ’omics, existing in sample preparation (better affinity rea- Published online: 6 December 2024
protein-inclusive multiomics methods, and the gents, labeling, barcoding, signal amplifica-
importance of next-generation computational tion, sectioning) and microscopy (resolution, References
tools for registering and integrating informa- field of view) will lead us to spatial proteom- 1. Baker, G. et al. Nat. Methods https://doi.org/10.1038/
s41592-024-02328-0 (2024).
tion from different modalities across volumes. ics with higher coverage, over larger 3D vol- 2. Ma, C. et al. Nat. Methods https://doi.org/10.1038/s41592-
Although the present capabilities of spatial umes, and with subcellular resolution or even 024-02438-9 (2024).
3. Marx, V. Nat. Methods https://doi.org/10.1038/s41592-024-
proteomics technologies are remarkable, we super-resolution, as discussed in our Methods
02536-8 (2024).
are also excited for the future of this field. We to Watch on subcellular spatial proteomics9 4. Bodenmiller, B. Nat. Methods https://doi.org/10.1038/
expect we will see the expanded application in this issue. With these data will come even s41592-024-02538-6 (2024).
5. Keren, L. & Bussi, Y. Nat. Methods https://doi.org/10.1038/
of these technologies toward growing exist- more insight into how healthy cells work in
s41592-024-02539-5 (2024).
ing and new atlas projects, with efforts being their rightful context within tissues and what 6. Quail, D. & Walsh, L. Nat. Methods https://doi.org/10.1038/
made concurrently to improve metadata han- changes when things go wrong. s41592-024-02542-w (2024).
7. Nordmann, T., Mund, A. & Mann, M. Nat. Methods
dling, quality control and democratization We are also excited for more than just spatial
https://doi.org/10.1038/s41592-024-02541-x (2024).
of these methods. In addition, we think the proteomics! We invite you to explore the rest 8. Fan, R. Nat. Methods https://doi.org/10.1038/s41592-024-
application of multiomics methods that add of our special issue content, which includes 02533-x (2024).
9. Strack, R. Nat. Methods https://doi.org/10.1038/
the most complementary information to what eight Methods to Watch about which we are s41592-024-02546-6 (2024).
is already present in spatial proteomics will especially enthusiastic. We sincerely wish you
continue to grow. We also expect that more is and yours a safe and happy holiday season and
more, and that technological improvements a happy new year.

nature methods Volume 21 | December 2024 | 2195–2196 | 2196