Leveraging antibody profiling for advanced healthcare insights

March 12, 2024 - Omics data, including genomics, metabolomics, proteomics, and more, play a critical role in the healthcare industry. With this data, providers and researchers can make treatment decisions, direct research to understand diseases, and guide drug development. While genomics and other types of omics data are becoming increasingly popular, limited tools are available for understanding data revealed from antibody profiles.

However, in January 2024, Infinity Bio launched the Molecular Indexing of Proteins by Self-Assembly (MIPSA) as part of its next-generation antibody profiling platform. LifeSciencesIntelligence sat down with H. Benjamin Larman, PhD, founder and Chief Science Officer at Infinity Bio, Associate Professor at Johns Hopkins School of Medicine, and Caroline Popper, MD, senior advisor and board member at the company, to discuss MIPSA, antibody profiling and the long-term benefits of this platform.

The Role of Antibody Profiling

Antibody profiling can be leveraged across multiple healthcare settings. It can be utilized in various disease areas, including infectious diseases, autoimmune disease research, vaccine development, allergy research, and cancer immunotherapy.

“We are entering the next big phase, after genetics and genomics, of understanding human health, disease, and disease processes. That is the need for a deeper understanding of immunology,” explained Popper.

She noted that today, we have advanced tools and techniques that can help researchers and clinicians better understand antibody profiles on individual and group levels, enhancing precision medicine. According to Popper, these profiles are a function of three major factors:

• Exposure to infectious agents
• Allergen exposure
• What factors the immune system has come to see as an invader

“This context is enormously important to understand human disease, progression, and even more importantly, how humans will respond to various therapeutic strategies.”

This knowledge can be applied in multiple aspects of healthcare, including discovering new disease mechanisms, understanding disease susceptibility and the risk of adverse events, and developing diagnostic tests and tools.

Popper also told LifeSciencesIntelligence that understanding antibody profiles allows researchers and drug developers to segment patient populations more precisely, providing more insight than genetics alone. Larman echoed Popper, emphasizing that individual omics measurements, including genomics, proteomics, metabolomics, and immunology measurements, play a piece in the puzzle.

MIPSA

Larman and Popper provided some background on the goal of MIPSA, how it functions, and how Infinity Bio can leverage some of the data it provides.

“From a scientific and more technical side, how do you read out the immune system?” posed Larman. “It turns out that antibodies are a record of our immune responses over time to all these things, including infectious agents, allergens, and autoimmune responses.”

One of the primary challenges was analyzing the data that antibody activity provided using a blood sample. Larman’s research and Infinity Bio’s team developed MIPSA to address that challenge.

“It uses self-assembly to create these large libraries of antigens that we can test for binding to each individual's antibody repertoire. We've set this up in an industrial strength setting to provide that information at scale in an affordable, reliable way,” he continued.

According to Infinity Bio, antibody profiling with MIPSA revolves around three critical steps:

1. Antigen library creation
2. Antibody–antigen library interaction
3. Decoding of information

Antigen Library Creation

Antigen library creation is one of the most critical steps in antibody profiling with MIPSA. It can be further broken down into multiple components.

First, it is critical to note that MIPSA can be used to develop two types of antigen libraries. One library type uses cloned open reading frames (ORFs) that code for full-length proteins.

On the other hand, Larman notes that they can also create libraries that express synthetic DNA oligonucleotides that encode peptide tiles.

 “[Infinity Bio] can generate libraries of sequences that encode peptides where the peptides tile across all the proteins that you care about, detecting immune responses,” he stated.

The next component is the self-assembly step of MIPSA, which allows researchers to attach a DNA barcode to each protein.

“We've developed this way that uses self-assembly in a cell-free expression system using a tag system called a halo tag and a halo ligand such that when this library is translated, the first thing they're making is this halo tag that will make a covalent bond with a DNA barcode.”

This process involves three primary steps:

1. Creation of the barcoded RNA library
2. Reverse transcription
3. Translation of the HaloTagged Antigen library.

Antibody–Antigen Interactions

“We use the antibodies from an individual to capture all the library members that stick to their antibodies, and then we use sequencing to read those barcodes, and we know which barcodes are attached to which peptides or proteins,” Larman added. “That's how we leverage the power of DNA synthesis on the one hand to make the libraries and DNA sequencing on the other hand to read it out.”

Decoding of Information

After the antibody–antigen complexes are formed, the researchers capture antibodies with the bound MIPSA and DNA barcode using magnetic beads. Once they have isolated the bound MIPSA library members, they can use a PCR to amplify the barcodes.

The Infinity Bio site notes, “High throughput DNA sequencing is used to count the number of MIPSA library member molecules captured in each sample. Proprietary software pipelines convert the sequencing count data into interpretable assay results.”

Implementing AI and Data Analytics

Popper noted that data science and analytics of the output of the MIPSA process are critical to the process. Today, the work is done in their laboratory setting; however, she anticipates that the proprietary data science Infinity Bio uses can be applied to multiple datasets in the future.

“It's a high dimensional data set that can benefit from all the tools that have been built over the years for analyzing these types of data sets,” noted Larman when prompted to discuss the role of artificial intelligence (AI) in MIPSA technology and antibody profiling.

He identified two areas where advanced data analytics technology can be used. One way is data extraction. He emphasized that these tools can be critical in how information or conclusions can be made from datasets, including antibody profiles, allowing the company to generate insight for the customer. The other way is integrating omics datasets with new antibody profiles.

Future Progress

Currently, Infinity only runs one shift at a time, but Popper told LifeSciencesIntelligence that they can run multiple shifts simultaneously.

“We've set up the company with a vision for high sample throughput and high capacity to serve what we expect to be a rapidly growing market in antibody profiling.”

“We've invested a lot in scaling up new library content and making complex libraries. That's one of Infinity Bio's unique features; we can develop custom antigen panels with our customers.”