# Unraveling the functional diversity of B cells in health and disease

> **NIH NIH DP2** · UNIVERSITY OF CHICAGO · 2024 · $492,000

## Abstract

The role of B cells in infectious disease, autoimmunity, and allergy is critical. Modern sequencing
technologies, such as single-cell RNA sequencing (scRNAseq) and spatial transcriptomics, have
emerged as powerful techniques for studying the transcriptional states of individual B cells in a variety
of biological contexts. These technologies generate massive amounts of complex data that
necessitate use of powerful, sophisticated computational methods. The analysis of such data is
hampered by numerous technical and biological biases embedded in the data. In scRNAseq, for
example, the non-uniform capture of cells along some developmental trajectory, as well as the
expression of multiple concurrent transcriptional programs, pose a challenge to current single cell
clustering and trajectory inference methods. These biases are exacerbated when studying B cell
compartments with complex dynamics, such as those found in lymphoid tissues. To address these
issues, we propose a novel toolbox of algorithms for modeling B cell activity that combines prior,
validated biological knowledge with computational algorithm design. In Aim 1, we develop tools to
elucidate temporal B cell developmental processes. And in Aim 2, we develop tools to elucidate B cell
spatial transcriptional programs. In Aim 3, apply our tools to a variety of important clinical scenarios,
such as mapping the immune correlates of higher affinity antibodies and characterizing the
heterogeneity observed in IBD. Overall, our research will create much-needed computational tools for
analyzing immune signals in scRNAseq and spatial transcriptomics data, as well as show that
incorporating prior knowledge greatly improves the ability of computational algorithms to reveal the
full spectrum of immune system changes that occur in response to vaccination, infection, and
immune-mediated diseases.

## Key facts

- **NIH application ID:** 10898058
- **Project number:** 5DP2AI177884-02
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Aly Azeem Khan
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $492,000
- **Award type:** 5
- **Project period:** 2023-08-02 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10898058

## Citation

> US National Institutes of Health, RePORTER application 10898058, Unraveling the functional diversity of B cells in health and disease (5DP2AI177884-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10898058. Licensed CC0.

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