Why is the human proteome important?
The Human Protein Atlas is one of the world’s largest biological databases, containing spatial expression profiles for all known proteins expressed in human organs and tissues.
It contains a vast amount of data gathered from a combination of proteomics and transcriptomics technologies such as antibody-based imaging, transcriptomics, and mass spectrometry. Each protein expression profile is accompanied by high-resolution images of tissue samples that have been manually annotated by experts forming a collection of labeled images for AI and machine learning efforts.
Recently, the Human Protein Atlas classified genes into clusters based on expression across the different tissues and cell types, followed by annotation of each cluster with assigned properties such as function, location, and specificity. Therefore, the database is a major resource for studying mRNA and protein expression from the perspective of single genes, tissues, cell types, and a body-wide or genome-wide perspective. The Human Protein Atlas program has already contributed to several thousand publications in the field of human biology and disease accelerating our understanding of human biology and its implications for disease.
Future direction
The HPA is updated every year and each new release contains new data and website functionalities. Recently, the addition of transcriptomics data based on high-throughput mRNA sequencing has increased the width and depth of the data enabling to study of protein expression at multiple levels. Today, technological advances such as high-throughput analyses for the detection, identification, and functional investigation of proteome offer more sensitivity, greater rapidity, and greater proteome coverage, replacing more traditional proteomics methods.
To give an example, immunohistochemistry methods have been the mainstay for spatial detection of protein expressions, and advancements such as fully automated multiplex immunofluorescence staining technologies that detect both RNA and protein expression simultaneously are generating a large amount of data rapidly.
The GeoMx® Digital Spatial Profiler
Extracting biological insights from spatial data is vital to advancing science. The RNA expression data in the human protein atlas is based on bulk RNA sequencing methods that use dissociated tissue samples losing key spatial information.
For spatial information, the RNA-seq data is supported by corresponding immunohistochemical staining images. NanoString’s GeoMx® DSP, a spatial multiomics technology, circumvents this problem and integrates both mRNA and protein detection using a combination of multiplex immunofluorescence imaging and in situ hybridization, and is compatible to work on FFPE tissue.
The GeoMx DSP can profile up to 18,000+ protein-coding genes without disturbing the native architecture of the tissue profiled.
The GeoMx DSP can profile up to 18,000+ protein-coding genes without disturbing the native architecture of the tissue profiled, thus providing spatial resolution. Further, the GeoMx DSP can quantify the levels of expression within regions of interest (ROIs) defined by tissue morphology and visualized with fluorescent-labeled antibodies. When coupled with readout from an NGS system, tens of thousands of targets can be profiled simultaneously, dramatically increasing the throughput of spatial analysis methods to better characterize tissue in less amount of time with the added advantage of keeping the tissue intact during the process. For instance, the GeoMx DSP system has been instrumental in generating a spatial organ atlas from six human organ systems: kidney, brain, intestine, liver, lymph node, and pancreas.
The CosMx™ Spatial Molecular Imager
The CosMx™ SMI system by NanoString compliments the GeoMx DSP and allows high plex imaging of both RNA and protein at single-cell or subcellular spatial resolution. The CosMx SMI provides imaging of hundreds or thousands of RNAs and about a hundred proteins within intact whole tissue sections, enabling the creation of a spatial cell atlas useful to extract deep biological insights and novel discoveries from one experiment.
The CosMx™ SMI and decoder probes are not offered and/or delivered to the Federal Republic of Germany for use in the Federal Republic of Germany for the detection of cellular RNA, messenger RNA, microRNA, ribosomal RNA and any combinations thereof in a method used in fluorescence in situ hybridization for detecting a plurality of analytes in a sample without the consent of the President and Fellows of Harvard College (Harvard Corporation) as owner of the German part of EP 2 794 928 B1. The use for the detection of cellular RNA, messenger RNA, microRNA, ribosomal RNA and any combinations thereof is prohibited without the consent of the President and Fellows of Harvard College (Harvard Corporation).