The advent of next-generation sequencing has led to the rise of novel gene expression profiling methods like spatial transcriptomics. How will this revolutionary approach, powered by high-quality multi-omics biospecimen, impact personalized immuno-oncology therapy in the future?
Next-generation sequencing (NGS) technologies have revolutionized the way scientific research is conducted, triggering new research paradigms and providing novel clinical insights.
Developed as a result of NGS in 2013, spatial transcriptomics is a groundbreaking molecular profiling method, which visualizes the location of gene activity within a tissue – the ‘where’, in parallel to studying gene expression patterns – the ‘what’.
Spatial transcriptomics: a holistic insight into cellular expression
Conventional RNA sequencing techniques can help identify gene expression activity in a tissue, but often destroy the tissue in the process. And while traditional visualization techniques, such as in situ hybridization, can capture localized gene expression patterns, they are limited to examining a few genes at a time.
Spatial transcriptomics builds on a combination of these methods: marrying the depth of information from tools such as sequencing, with the morphological context of expression patterns for multiple genes, while retaining the structural integrity of the tissue.
“Visualizing what kind of cells are expressing which genes can provide valuable insights in a range of scientific specialties, ranging from biomarker discovery, investigation of cellular development or tumor immunology, to brain mapping for neurology research,” explained Maike Priester, Director of Product Management and Marketing at the German oncology company Indivumed.
Spatial transcriptomics techniques have quickly gained a strong footing in the scientific community and have even been picked up by the industry in the relatively short time frame they have been around, marveled Priester.
“Backed by the fast-paced research to improve data resolution in the field, biotech companies like 10x Genomics have developed techniques that provide spatial visualization of genes down to a cellular level. Considering that this resolution was still at a regional level within tissues less than seven years ago, this is a remarkable development,” said Nicole Kerstedt, Director of the Genomics Department at Indivumed.
Moreover, spatial transcriptomics can be used in conjunction with other scientific advances in the field of multi-omics, which provides insights using datasets from different biological analyses focused on the genome, proteome, microbiome, and more. Combining different techniques in such a manner can add a high dimensionality to clinical research.
Due to the rich contextual information that spatial transcriptomics can provide, the approach has become increasingly popular in the immuno-oncology field. The cancer microenvironment is a particularly complex one and is made up of many diverse cell types which exhibit unique gene expression patterns that can vary over time or between tumors.
“Spatial information in transcriptomics can highlight gene expression clusters within a tumor section, providing an insight into the complex cellular cross-talk in cancer microenvironments,” Priester elaborated.
“This can be key in understanding tumor development, determining tumor malignancy, and identifying new therapeutic targets to enhance the effectiveness of cancer immunotherapy.”
This is not to say that spatial transcriptomics is free from its share of hurdles today. The high dimensionality brings with it the challenge of tackling large datasets and the requirement of powerful visualization programs compatible with big data.
The high demand due to the versatile applicability of spatial transcriptomics also means researchers face constant pressure to improve cellular data resolution.
Spatial transcriptomics techniques are also yet to be optimized for high-throughput research methods, a hurdle that is essential to overcome before they can be effectively applied in large-scale drug discovery and development, Kerstedt pointed out.
The importance of the ‘right’ biospecimen in spatial transcriptomics
Despite such hurdles, spatial transcriptomics techniques in use today, along with the kits and workflows that enable them, are very comprehensive, asserted Priester. Key to this has been the use of high-quality biospecimens.
“The outcome of your research is only as good as the biospecimen you put in. Good quality samples are required to generate reliable results that reflect molecular reality,” elaborated Priester.
“Developing drugs or companion diagnostics on biased information collected in a non-optimal manner can lead to massive mis-investments for pharma firms while doing the scientific community and all of their hard work a huge disservice.”
Biospecimens that have been outside of the body for too long or otherwise modified, can lose vital information. This is even more important in oncology, where tumor cells extracted from the body can still undergo morphological or physiological changes due to continued contact with oxygen. Such changes can mean that experimental results are altered: wrong pathways or incorrect biomarkers are picked up.
To control this, many academic and commercial biobanks today have standard operating procedures on sample fixation, processing, and storage. However, since many firms outsource biospecimen collection, sample variability may be introduced at the very first step of sample collection, irrespective of the protocol in the steps that follow.
Multi-omics specimen: the key to high-quality data
Given the importance of biospecimen quality and integrity in methods like spatial transcriptomics, the Indivumed team has put together a standardized ISO-certified protocol, based on which they have built a high-quality cancer tissue and fluid biobank that has grown in the last 20 years.
Dubbed as multi-omics biospecimen, the cancer samples in Indivumed’s biobank are collected by in-house nurses from partner clinics across the globe to ensure comparability in terms of sample collection and processing.
Along with the tumor samples, ‘normal’ tissues adjacent to the tumor, as well as plasma, serum, or urine, are also collected to provide a more holistic insight into the physiological environment in the patient. The tissue samples are fixed and processed within 10 minutes of surgical resection from a patient following a stringent protocol that preserves the original nature of the tumor.
“Our biobank offering comes with comprehensive clinical data. This includes patient specifications such as age, nationality, medical history, diet, smoking status, as well as follow-up and outcome data collected by our own after-care in-house team,” explained Kerstedt.
Indivumed supports a wide variety of immuno-oncology research efforts with its banked and prospective collected biospecimens, with a focus on pre-clinical, translational (for phase I and II studies), and retrospective analysis.
Indivumed’s latest venture is a partnership with 10x Genomics as a certified service provider for 10x Genomics’ spatial transcriptomics solution, Visium Spatial Gene Expression.
Elaborating on the partnership, Kerstedt said, “The Visium method is outstanding and provides valuable insights on molecular cancer development and its pathology. Being a certified service provider allows us to not only optimize and conduct the requested workflows for our customers but also interpret the data on request.”
“With the needs of our customers in mind, we are also starting to implement other technologies in the 10x Genomics method portfolio, such as the single-cell gene expression analysis. All of these techniques hold the promise of robust outcomes when paired with our multi-omics specimen.”
The future of spatial transcriptomics and multi-omics biospecimen
Cancers are highly individual diseases. Priester believes that illuminating biological correlations in cancer is the key to moving away from one-size-fits-all chemotherapy treatments to personalized medicine.
Spatial transcriptomics, with developments in digital technology and machine learning, could serve to propel this shift further. In the near future, the information from these tools could potentially enhance diagnostic accuracy and enable optimal treatment decision-making suited to each individual patient.
Recognizing this potential, leading contract research organizations in the field of oncology like Indivumed are investing heavily in digital pathology and AI techniques to facilitate and standardize sample readouts and enhance pattern identification.
“With each individual tumor being different, it becomes crucial to look in-depth with support from the latest techniques. This is where we see our services and biospecimen making a difference for our customers and for our patients, in our quest to realize personalized medicine,” concluded Priester.
Here’s how you can partner with Indivumed to optimize your spatial transcriptomics workflow.
To understand more on how the latest techniques can help investigate spatial gene expression differences, click here to read about Indivumed’s spatial transcriptomics services.
Header image via Shutterstock.com. All other images courtesy of Indivumed.