Swedish Researchers Publish High-resolution Single-cell Transcriptomic Map of Human Tissues in Findings That May Advance Diagnostics and Medical Laboratory Testing
Teams from multiple Swedish organizations are investigating the relationship of protein-coding genes to antibodies
Scientists in Sweden are discovering new ways to map the expression of genes in cells, tissues, and organs within the human body thanks to advances in molecular profiling. Their study has successfully combined the analysis of single-cell transcriptomics with spatial antibody-based protein profiling to produce a high-resolution, single-cell mapping of human tissues.
The data links protein-coding genes to antibodies, which could help researchers develop clinical laboratory tests that use specific antibodies to identify and target infectious disease. Might this also lead to a new menu of serology tests that could be used by medical laboratories?
This research is another example of how various databases of genetic and proteomic information—different “omics”—are being combined to produce new understanding of human biology and physiology.
Scientists from the KTH Royal Institute of Technology in Stockholm, Uppsala University, Karolinska Institute, and the Karolinska University Hospital in Sweden, the Arctic University of Norway, and other institutions, used both RNA sequencing and antibody-based profiling to formulate a publicly-available map of 192 human cell types.
The researchers published their findings in the peer-reviewed journal Science Advances, titled, “A Single–Cell Type Transcriptomics Map of Human Tissues.” They wrote, “the marked improvements in massive parallel sequencing coupled with single-cell sample preparations and data deconvolution have allowed single-cell RNA sequencing (scRNA-Seq) to become a powerful approach to characterize the gene expression profile in single cells.”
In a Human Protein Atlas (HPA) project press release, Director of the HPA consortium and Professor of Microbiology at Royal Institute of Technology in Stockholm, Mathias Uhlén, PhD, said, “The [Science Advances] paper describes an important addition to the Human Protein Atlas (HPA) which has become one of the world’s most visited biological databases, harboring millions of web pages with information about all the human protein coding genes.”
Distinct Expression Clusters Consistent to Similar Cell Types
To perform their research, the scientists mapped the gene expression profile of all protein-coding genes across different cell types. Their analysis showed that there are distinct expression clusters which are consistent to cell types sharing similar functions within the same organs and between organs of the human body.
The scientists examined data from non-diseased human tissues and organs using three main criteria:
- Publicly available raw data from human tissues containing good technical quality with at least 4,000 cells analyzed and at least 20 million read counts by the sequencing for each tissue.
- High correlation between pseudo-bulk transcriptomics profile from the scRNA-Seq data and bulk RNA-Seq generated as part of the Human Protein Atlas (HPA).
- High correlation between the cluster-specific expression and the expected expression pattern of an extensive selection of marker genes representing well-known tissue- and cell type-specific markers, including both markers from the original publications and additional markers used in pathology diagnostics.
According to the HPA press release, “across all analyzed cell types, almost 14,000 genes showed an elevated expression in particular cell types, out of which approximately 2,000 genes were found to be specific for only one of the cell types.”
The press release also states, “cell types in testis showed the highest numbers of cell type elevated genes, followed by ciliated cells. Interestingly, only 11% of the genes were detected in all analyzed cell types suggesting that the number of essential genes (‘house-keeping’) are surprisingly few.”
Omics-based Biomarkers for Accurate Diagnosis of Disease
The goal of this venture is to map all the human proteins in cells, tissues, and organs through various “omics” technologies. As Dark Daily wrote in “Spatial Transcriptomics Provide a New and Innovative Way to Analyze Tissue Biology, May Have Value in Surgical Pathology,” omics have the potential to deliver biomarkers which can be used for earlier and more accurate diagnoses of diseases and health conditions. Omics, such as genomics, epigenomics, proteomics, metabolomics, metagenomics, and transcriptomics, are taking greater roles in precision medicine diagnostics as well.
The Human Protein Atlas is the largest and most comprehensive database for spatial distribution of proteins in human tissues and cells. It provides a valuable tool for researchers who study and analyze protein localization and expression in human tissues and cells.
Ongoing improvements in gene sequencing technologies are making research of genes more accurate, faster, and more economical. Advances in gene sequencing also could help medical professionals discover more personalized care for patients leading to improved outcomes. A key goal of precision medicine.
One of the conclusions to be drawn from this work is that clinical laboratories and anatomic pathology groups will need to be able to handle immense amounts of data, while at the same time having the capabilities to analyze that data and identify useful patterns that can help diagnose patients earlier and more accurately.
It is another example of how and why those medical laboratories that succeed going forward will have robust laboratory information management systems (LIMS). Forward-looking lab leaders may want to make larger investments in their lab’s health information technology (HIT).