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Clinical Laboratories and Pathology Groups

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Clinical Laboratories and Pathology Groups

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Spatial Transcriptomics Provide a New and Innovative Way to Analyze Tissue Biology, May Have Value in Surgical Pathology

Newly combined digital pathology, artificial intelligence (AI), and omics technologies are providing anatomic pathologists and medical laboratory scientists with powerful diagnostic tools

Add “spatial transcriptomics” to the growing list of “omics” that have the potential to deliver biomarkers which can be used for earlier and more accurate diagnoses of diseases and health conditions. As with other types of omics, spatial transcriptomics might be a new tool for surgical pathologists once further studies support its use in clinical care.

Oncologists and anatomic pathologists are increasingly becoming aware of the power of computer image analysis algorithms that use artificial intelligence (AI) when analyzing digital pathology images, such as whole-slide imaging (WSI), and radiology images. They also are aware that various omics, such as genomics, epigenomics, proteomics, metabolomics, metagenomics, and transcriptomics, are taking greater roles in precision medicine diagnostics as well.

Among this spectrum of omics is spatial transcriptomics, or ST for short.

Spatial Transcriptomics is a groundbreaking and powerful molecular profiling method used to measure all gene activity within a tissue sample. The technology is already leading to discoveries that are helping researchers gain valuable information about neurological diseases and breast cancer.

Marriage of Genetic Imaging and Sequencing

Spatial transcriptomics is a term used to describe a variety of methods designed to assign cell types that have been isolated and identified by messenger RNA (mRNA), to their locations in a histological section. The technology can determine subcellular localization of mRNA molecules and can quantify gene expression within anatomic pathology samples.

In “Spatial: The Next Omics Frontier,” Genetic Engineering and Biotechnology News (GEN) wrote, “Spatial transcriptomics gives a rich, spatial context to gene expression. By marrying imaging and sequencing, spatial transcriptomics can map where particular transcripts exist on the tissue, indicating where particular genes are expressed.”

In an interview with Technology Networks, George Emanuel, PhD, co-founder of life-science genomics company Vizgen, said, “Spatial transcriptomic profiling provides the genomic information of single cells as they are intricately spatially organized within their native tissue environment.

“With techniques such as single-cell sequencing, researchers can learn about cell type composition; however, these techniques isolate individual cells in droplets and do not preserve the tissue structure that is a fundamental component of every biological organism,” he added.

“Direct spatial profiling the cellular composition of the tissue allows you to better understand why certain cell types are observed there and how variations in cell state might be a consequence of the unique microenvironment within the tissue,” he continued. “In this way, spatial transcriptomics allows us to measure the complexity of biological systems along the axes that are most relevant to their function.”

George Emanuel, PhD

“Although spatial genomics is a nascent field, we are already seeing broad interest among the community and excitement across a range of questions, all the way from plant biology to improving our understanding of the complex interactions of the tumor microenvironment,” George Emanuel, PhD (above), told Technology Networks. Oncologists, anatomic pathologists, and medical laboratory scientists my soon see diagnostics that take advantage of spatial genomics technologies. (Photo copyright: Vizgen.)

According to 10x Genomics, “spatial transcriptomics utilizes spotted arrays of specialized mRNA-capturing probes on the surface of glass slides. Each spot contains capture probes with a spatial barcode unique to that spot.

“When tissue is attached to the slide, the capture probes bind RNA from the adjacent point in the tissue. A reverse transcription reaction, while the tissue is still in place, generates a cDNA [complementary DNA] library that incorporates the spatial barcodes and preserves spatial information.

“Each spot contains approximately 200 million capture probes and all of the probes in an individual spot share a barcode that is specific to that spot.”

“The highly multiplexed transcriptomic readout reveals the complexity that arises from the very large number of genes in the genome, while high spatial resolution captures the exact locations where each transcript is being expressed,” Emanuel told Technology Networks.  

Spatial Transcriptomics for Breast Cancer and Neurological Diagnostics

An open-access article published in the journal Breast Cancer Research, titled, “Identification and Transfer of Spatial Transcriptomics Signatures for Cancer Diagnosis,” stated that spatial transcriptomics (ST) could successfully detect breast cancer expression signatures from annotated tissue sections.

In that paper, the authors wrote “we envision that in the coming years we will see simplification, further standardization, and reduced pricing for the ST protocol leading to extensive ST sequencing of samples of various cancer types.”

Spatial transcriptomics is also being used to research neurological conditions and neurodegenerative diseases. ST has been proven as an effective tool to hunt for marker genes for these conditions as well as help medical professionals study drug therapies for the brain.

“You can actually map out where the target is in the brain, for example, and not only the approximate location inside the organ, but also in what type of cells,” Malte Kühnemund, PhD, Director of Research and Development at 10x Genomics, told Labiotech.eu. “You actually now know what type of cells you are targeting. That’s completely new information for them and it might help them to understand side effects and so on.”

The field of spatial transcriptomics is rapidly moving and changing as it branches out into more areas of healthcare. New discoveries within ST methodologies are making it possible to combine it with other technologies, such as Artificial Intelligence (AI), which could lead to powerful new ways oncologists and anatomic pathologists diagnose disease.

“I think it’s going to be tricky for pathologists to look at that data,” Kühnemund said. “I think this will go hand in hand with the digital pathology revolution where computers are doing the analysis and they spit out an answer. That’s a lot more precise than what any doctor could possibly do.”

Spatial transcriptomics certainly is a new and innovative way to look at tissue biology. However, the technology is still in its early stages and more research is needed to validate its development and results.  

Nevertheless, this is an opportunity for companies developing artificial intelligence tools for analyzing digital pathology images to investigate how their AI technologies might be used with spatial transcriptomics to give anatomic pathologists a new and useful diagnostic tool. 

—JP Schlingman

Related Information:

What is Spatial Transcriptomics?

Spatial: The Next Omics Frontier

Spatial Transcriptomics Puts More Biology on the Map

Exploring Tissue Architecture Using Spatial Transcriptomics

Trends, Applications and Advances in Spatial Transcriptomics

Spatially Resolved Transcriptomes—Next Generation Tools for Tissue Exploration

Identification and Transfer of Spatial Transcriptomics Signatures for Cancer Diagnosis

Spatial Transcriptomics: A Window into Disease

Supreme Court Strikes down Myriad Gene Patents in Unanimous Vote; Decision Is Expected to Benefit Clinical Pathology Laboratories

Pathologists and clinical laboratory managers can expect to see an expansion of genetic testing in the wake of the Supreme Court’s decision in the Myriad case

Pathologists and clinical laboratory professionals got a major victory on June 13. That’s when the United States Supreme Court (SCOTUS) ruled 9-0 to end the 30-year-old practice of awarding patents on human genes. The unanimous decision invalidates certain hotly contested patents held by Myriad Genetics, Inc., (NASDAQ: MYGN) on the BRCA1 and BRCA2 genes.

Moreover, this Supreme Court decision also opens the doors to other medical laboratories  to develop their own diagnostics around the BRCA genes and compete for breast-cancer testing market share. (more…)

Non-Invasive Early Diagnostic Pathology Test for Gastric Cancer Developed by University Of Georgia Researchers

New cancer test may be as easy as a home-use pregnancy test

Early detection of certain types of cancer may eventually become as easy as taking a home pregnancy test. That’s the prediction of researchers who are developing a non-invasive early diagnostic test for gastric cancer that would not require a pathologist  to assess a tissue specimen. Instead, this test detects biomarkers in the patient’s urine.

Surgical pathologists will recognize the potential of this discovery to create new tools for diagnosing cancer at earlier stages—and without the need to collect a tissue specimen. For clinical laboratories, the possibility of a urine-based test that could accurately detect different cancers would make it possible for them to offer diagnostic assays based on this technology to office-based physicians.

(more…)

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