Setting a New Standard for Spatial Omics: An Integrated Multiomics Approach

By James DeRosa, MPH

Trifecta of Spatial Biology diagram
The trifecta of spatial biology is a concept where it is extremely difficult to simultaneously improve resolution, plex and throughput. Normally we accept the fact that any two aspects can be improved, but the third suffers.

Technologies are in a constant state of development. When we think of mobile phones, we expect a new generation every year. Keeping up with demand in technology is daunting but necessary for continued progress. In the field of spatial biology we see a similar need. Innovative technologies lose value over time. It’s part of the process as we learn what we don’t know and are thereby inspired to create something new capable of answering the novel questions being asked. What drives innovation in spatial biology is the pursuit of a truly comprehensive understanding of a tissue. What blocks innovation in this area, however, is the trifecta of Plex, throughput, and resolution. It seems that we can only improve two of these elements at once, but not all three.

With the introduction of PhenoCycler™-Fusion, Akoya Biosciences broke the iron triangle of spatial biology based on speed. The PhenoCycler™ Fusion system is the fastest spatial biology solution that enables ultrahigh-plex whole slide spatial phenotyping with single-cell resolution by integrating automated fluidics and iterative imaging. Capable of imaging 1 million cells in 10 minutes, the system enables unbiased spatial phenotyping of tissues, considering every single cell on the entire slide.

Tissue biology is undeniably complex and multifaceted. To gain mechanistic insights into the complex processes and pathways orchestrated in tissue, a multiomics approach is a must. However, the method of measuring more analytes via multiomics must not only be workable, but also maintain the plex throughput resolution trifecta.

Julia Kennedy-Darling, PhD
Julia Kennedy-Darling, PhD
Senior Director of Research and Development
Akoya Life Sciences

Like other players, Akoya becomes multiomic. To gain an additional perspective on multiomics becoming the new gold standard and what sets Akoya apart as an industry leader, I sat down with Dr. Julia Kennedy-Darling, senior director of research and development at Akoya. She received her training in Professor Garry Nolan’s lab at Stanford, where she was part of the pioneering team of scientists that developed the Co-detection by Indexing (CODEX) solution, now known as PhenoCycler. She joined Akoya Biosciences as a second collaborator to lead the R&D effort to commercialize PhenoCycler. Over the past five years she has helped fuel the dramatic expansion of the field of spatial biology and continues to be at the forefront of innovation ushering in a new era of multiomic technologies.

Julia, thank you for coming to me today. Before we dive into multiomics, I’ve heard a lot about the speed of the recently launched PhenoCycler-Fusion. Can you explain how that affected you and your team at Akoya?

As biotechnology developers, we tend to delve into the intricacies of the chemistry required to meet a specific need. But the biggest obstacle for us is the time it takes to complete an Ultrahigh Plex experiment. This is where PhenoCycler-Fusion has had the greatest impact. Before PhenoCycler-Fusion we were limited to smaller tissue regions or compromised resolution or an experiment lasted a whole week. Now we run experiments every day. This has changed our lives in research and development. Ultra-high plex assays have become the norm in the laboratory. The impact on the scales has been huge and has really enabled us to drive innovation. For a scientist, there are few things more satisfying than getting your data back in a day.

R&D team at Akoya
Special thanks to the Akoya R&D team.

So why Spatial Multiomics and why now?

The first part is obvious. Imaging-based spatial multiomics has the potential to reveal cell state and cellular phenotypes. In situ quantification of RNA and proteins provides a systems biology view of the tissue microenvironment, allowing us to extrapolate their transcriptomic insights and hypotheses to whole tissue and to observe their role in the interplay between cells in their pristine state. It is this step that connects the RNA to the protein to cellular organization and behavior. As I said earlier, ultra-high plexus spatial proteomics assays have become the norm at Akoya. So the next logical step was to add an additional layer of insight that would allow the RNA to capture maximum insights from the entire tissue at single-cell resolution.

Obviously, the idea of ​​more powerful technologies and multiomics assays is exciting, but with more data comes more challenges. How to overcome data bottlenecks and can multiomics assays become a viable gold standard in the average lab?

That’s a great question that we think about often! PhenoCycler-Fusion is all about identifying key cell types and mapping them unbiasedly across whole tissue sections to discover key signatures otherwise undetectable with bulk or dissociative technologies. Add RNA data to the equation, however, and now we’re dealing with really massive amounts of data. To address this problem, Akoya is investing heavily in software solutions that support AI-driven analysis and algorithms for a comprehensive understanding of underlying biological systems. Multiomic assays are likely to become the gold standard once we identify the most biologically relevant targets and our workflows are fast and robust enough to support these assays.

The aim is to generate new biomarkers or diagnostic signatures from this data; How do you see these more sophisticated assays making their way into clinical practice?

This is the part that really excites me! There is clearly a need for new signatures for both diagnosis and treatment. The real value of Akoya’s platform, like others in this field, is the ability to discover new signatures composed of both cell types and their spatial localization. Akoya’s solutions can be used with large panels to discover new signatures and can also be used to verify those signatures at high throughput. Both sides of the continuum are needed to meet clinical needs – Akoya is focused on ensuring we have solutions across the spectrum to deliver on the clinical promise of spatial biology.