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We recently had the opportunity to chat with Alex Ward, PhD, Principal Consultant, Arta Bioanalytics to discover more about his work in developing transcriptomics and metabolomics data interpretation for the cultivated meat sector. As a specialist in multi-omics approaches, Alex is driving R&D, production and regulatory processes for the industry. Below are Alex’s responses to a few questions we asked, sharing his knowledge with the SCIEX community to drive the future of cultivated meat.

Question 1: What are the major workflow/processing steps you deal with?

In my current and previous roles in cultivated meat, I have carried out a broad range of workflow and processing stages in mass spectrometry, extending from initial sample preparation to sophisticated data interpretation; however, my primary focus is on the analytical aspects and making biological sense out complex multiomics data.

In making sense of complex cell biology and bioprocess data, I have found that, often, I will be using discovery and targeted metabolomics workflows as a primary data source, often combined with transcriptomics, to give a holistic picture of the cell. For this, I have predominantly used high-resolution MS instruments, like QTOF or Orbitrap systems. To answer separate questions about unique parts of cultivated meat product development, I have also previously performed data interrogation in proteomics and lipidomic workflows using lower resolution triple quad systems.

For data processing, I generally prefer off-line tools over vendor-specific software’s due to their flexibility, which facilitates more effective data processing, quality control, quantification, and visualisation. This approach typically involves the use of automated or batch processing tools and open-source software, allowing for a deeper interrogation and interpretation of the data.

Question 2: Having worked closely with the cultivated meat industry, where do you see the main mass spec applications today and in the future?

Mass spec has significant applications across the cultivated meat value chain. In particular, MS techniques can be leveraged for various stages of the R&D, production and regulation pipelines. In R&D, multiomics using MS (for discovery proteomics, lipidomics and metabolomics) can provide significant value for the optimisation of cell-lines, culture media and bioprocess, with each omic tool providing unique value depending on the question that the researcher has. For instance, discovery and targeted metabolomics can be used as a tool to rapidly develop media formulations for cultivated meat, both by analysis of metabolite profiles inside the cell (understanding metabolic pathways impacted during culture) and analysis of spent media (what components the cells have used up in the media during culture). Into the future, I envisage the use of single-cell omics tools being profoundly useful for cultivated meat cell line and media development, for everything from tasty cell clone selection to ultra lean media development.

Cultivated meat regulation is still evolving. However, there are areas of regulation where MS is currently widely used. In particular for monitoring secondary metabolites and other inputs in media that are considered risky by regulators. This includes quantification of growth factors, at risk product input components or unwanted contaminants, to ensure that cultivated meat products are safe for consumption and comply with stringent safety standards. In addition, proteomics plays a critical role in regulation by enabling the quantification of potential allergens in cultivated meat products. This is essential for food safety, as it ensures that allergen levels are kept below thresholds that could pose health risks to sensitive individuals.

Regarding production, the application of a Process Analytical Technology (PAT) framework—similar to what is employed in the pharmaceutical industry—is uncertain for cultivated meat. Integrating such a framework could potentially offer a systematic approach to enhancing product quality and consistency through real-time quality control, but given the cost constraint for food production, it is possible the industry will not progress down that path.

Question 3: What informatics tools do you see cultivated meat researchers using regularly?

In the cultivated meat industry, where standardised informatics tools are yet to be established, researchers are adapting and innovating with a variety of computational resources. Several larger companies have begun investing in in-house bioinformatics teams, indicative of a trend towards developing custom tools and pipelines tailored to specific research and production needs.

From my experience, there are several free and open-source tools that I find particularly valuable for research in this field. For instance, MultiABLER, developed by a colleague, is an R pipeline that facilitates the accurate interrogation of lipidomics and metabolomics data. This tool is exceptionally useful for integrating and analysing complex datasets, providing insights into the lipid and metabolic profiles of cultivated meats. Another tool I’ve used extensively is MS-DIAL, which is excellent for metabolomics and lipidomics as well. Developed by researchers at RIKEN, MS-DIAL stands out for its robust visualisation capabilities, though it might require more rigorous data processing steps using other tools. MetaboAnalyst is another indispensable tool for me, offering comprehensive functionality for statistical analysis, functional analysis, and data visualisation. This platform is incredibly user-friendly and supports a wide range of data inputs, making it a go-to resource for metabolomic studies.

For proteomics, MaxQuant is a mainstay for my data processing, and I often pair it with custom R pipelines for further analysis and visualisation, tailoring the workflow to meet specific objectives. Furthermore, I’ve found the proteomics analysis software developed by Mass Dynamics to be particularly effective, offering flexibility and powerful functionality for advanced proteomic analyses.

Beyond these tools, much of my work involves custom-built pipelines, especially for later stages of statistical analysis and visualisation. These bespoke solutions are crucial for addressing the unique challenges and opportunities in cultivated meat research, allowing for tailored approaches that enhance our understanding and innovation in this burgeoning field.

Question 4: What obstacles do you often face when processing data and how do you overcome those?

Data processing in the cultivated meat industry presents several unique challenges, primarily due to its innovative nature and the use of non-traditional species.

Much of the work in cultivated meat involves species that are not traditional model organisms, which means there’s little precedent or prior research to lean on. This is especially problematic in proteomics, transcriptomics, and genomics, where we often encounter poorly annotated or entirely absent genome builds. A significant challenge arises from the lack of comprehensive sequence information; many obscure animal proteomes are also incomplete, making it difficult to cover all protein isoforms when building mass spectrometry methods. To navigate these issues, I sometimes pivot towards metabolomics as a primary discovery tool. Metabolites tend to be conserved across species, offering a more straightforward path for analysis. However, when detailed genome-related insights are crucial, I resort to homology-based approaches to bridge gaps in sequence data.

As the cultivated meat sector is relatively nascent, there’s no established standard for many analytical procedures, which complicates data analysis and regulatory compliance across different countries. To tackle this, I work closely with colleagues and regulatory bodies to help develop and advocate for standardised methods and protocols that can be universally accepted.

A common necessity in R&D and regulation is to compare cultivated meat to traditional meat, posing significant analytical challenges due to the complex and varied matrices (tissue or cell) for mass spectrometry. This comparison is crucial for market acceptance and regulatory approval, ensuring that cultivated products meet or exceed the quality and safety of conventional meats. To address this, sophisticated sample preparations are needed, as well as analytical techniques that enhance sensitivity and specificity, allowing for accurate comparisons.