Case Study: Quotient Tx’s Novel Approach to Drug Development
Leveraging DNA-Based immune profiling with our technology to accelerate target discovery
Company: Quotient Tx
Industry: Biotech
Location: United Kingdom and United States
Background:
Founded by Flagship Pioneering, Quotient Therapeutics develops breakthrough medicines informed by natural somatic genetic diversity present in patients. Through the Company’s integrated somatic genomics and computational technologies, they gain unbiased, unprecedented resolution into disease-causal drug targets that they leverage to design and develop first-in-class therapies.
Objective:
To study the somatic mutations for a rare autoimmune condition, the team set out to gain a better understanding of the immune cell landscape - a critical step in identifying the right cell types to target with therapies. Their goal was to leverage somatic genomic data to characterize the presence and diversity of T-cell and B-cell receptors (TCRs and BCRs), enabling more precise and confident target identification for drug development.
Challenge:
In pursuit of their goal, the Quotient Tx team performed deep exome sequencing on mixed populations of cells. However, they faced a significant challenge: while they could generate high-quality DNA sequencing data, identifying the specific composition of the T and B cells within their samples was problematic:
Heterogeneous Cell Populations: The cell populations analyzed contained a mixture of cell types, making it difficult to discern which immune cells were present.
Data Utilization Gap: The team had generated extensive somatic genomic data, but needed a solution to fully understand the immune context of their samples.
Lack of Viable Tools: Existing tools failed to deliver actionable insights, especially when it came to characterizing TCR and BCR sequences.
“We had deep exome sequencing on a collection of cells, but didn’t have high confidence in the different cell types present. Could we use the data we were already generating to get an answer?”
Solution:
Quotient Tx adopted MiXCR, the leading immune analysis software, to help bridge the gap between raw DNA sequencing and immune cell characterization. MiXCR enabled the team to:
Quantify T and B Cell Populations: By extracting and assembling T cell receptor (TCR) and B cell receptor (BCR) clonotypes directly from their deep exome sequencing data, the team was able to accurately estimate the relative abundance of T and B cell. This approach provided quantitative immune cell composition data without additional assays, enabling direct correlation of immune repertoire diversity, clonal expansion patterns, and somatic mutation profiles, deepening the understanding of the immune response.
Characterize Diversity: MiXCR provided insights into the polyclonal nature of the immune repertoire, which is crucial in understanding biological complexity and therapeutic targeting.
“The MiXCR pipeline was computationally lightweight, adding very little to our overall execution times.”
Results & Impact
To validate the results, Quotient Tx ran benchmark tests comparing MiXCR-derived data to RNA-Seq datasets. The results confirmed:
Strong concordance between MiXCR and RNA-Seq deconvolution: Correlation plots comparing immune cell fractions quantified by MiXCR (y-axis) and RNA-Seq deconvolution via BayesPrism (x-axis) across multiple LCM samples showed high alignment, indicating consistency between DNA- and RNA-based approaches. (Figure 1)
Validation of MiXCR for immune repertoire profiling: These results support the utility of MiXCR as a dependable tool for immune cell quantification and repertoire characterization using DNA sequencing data.
“Our experience with MiXCR has been very positive. Even for a unique use case like ours, it worked well. We’d recommend it to anyone looking to characterize immune repertoires.”
- Matthew Young, Head of Target Data Science
By unlocking immune repertoire data from their existing exome sequencing workflows, Quotient Tx was able to unlock critical immunological information without the need for additional experiments—saving both time and resources.
Ready to unlock faster, deeper immunology insights?
Now you can access MiXCR on Platforma, a user-friendly bioinformatics platform, empowering your team to move seamlessly from raw NGS data to actionable results—without writing a single line of code. Platforma is free for academic use, or contact us at licensing@milaboratories.com to get started.