PathoPlex technology maps protein patterns across human organs

Each organ in the human body contains different types of cells arranged in specific ways.

These arrangements aid protein interactions, which drive important functions such as nutrient and waste processing in the liver and kidneys or neuron function in the brain.

Abnormal changes in protein levels and patterns can result in diseases.

Understanding protein organization can improve treatments and minimize disease symptoms.

In a study published in Nature, a global team of researchers developed a new technology called pathology-oriented multiplexing, or PathoPlex, to map more than 140 different proteins across 40 tissue samples.

They used PathoPlex to analyze tissue samples from people with diabetic kidney disease and identified disease-specific protein patterns.

The location of proteins in tissues can be visualized using antibodies with fluorescent tags that bind to specific proteins and glow under a microscope.

However, the lack of high quality antibody panels has hindered research efforts on organ-level protein expression.

The team developed PathoPlex by combining images from multiple protein-bound antibodies and using a software program that could interpret patterns across several tissues.

The system was optimized to map more than 140 different proteins from at least 40 biopsy specimens.

“PathoPlex paves the way towards understanding and imaging complex tissues in human diseases like diabetes,” said Matthias Kretzler, professor of internal medicine and member of Caswell Diabetes Institute, who was a part of the team.

“We can finally develop atlases that describe changes in protein functions and how to improve them with new treatments.”

As proof of concept, PathoPlex was used to analyze biopsy samples from people with diabetic kidney disease.

The researchers were able to link protein expression to organ dysfunction and identify healthy protein patterns in groups of cells that work well and those that are associated with disease in damaged cells.

PathoPlex also revealed kidney stress-related cell changes in people with type 2 diabetes before their kidneys showed any signs of disease.

The readouts assessed how these tissues would respond to specific drug treatments, suggesting that the technology could eventually accelerate both diagnosis and treatment timelines for patients.