Streamline clinical immune repertoire analysis with CLC Genomics Workbench

As clinical labs face increasing demands to analyze complex immune repertoires, accurate and efficient software tools have become essential. CLC Genomics Workbench offers labs a comprehensive solution, combining speed, ease, and precision in immunogenomic data interpretation.

Today, a growing number of clinical labs are incorporating immune repertoire analysis to investigate the diversity and clonality of B-cell and T-cell receptors, which provides insights into the immune system's function. By leveraging next-generation sequencing (NGS) and specialized bioinformatics tools, labs can analyze the immune response to diseases, monitor immune-related disorders, and assess the effectiveness of treatments like immunotherapies. This approach holds promise for personalized medicine, offering deeper understanding of immune responses in conditions such as cancer, autoimmune diseases, and infections, leading to more precise and targeted clinical interventions. In this article, learn how clinical labs can use CLC Genomics Workbench to simplify the traditionally complex immune repertoire analysis and deliver high-quality clinical insights.

B-cell reception (BCR) reconstruction

B-cell receptor (BCR) reconstruction refers to the process of reconstructing the sequences of BCRs from genomic or transcriptomic data. BCRs are proteins on the surface of B-cells that bind to antigens, initiating the immune response. Each B-cell has a unique BCR due to V(D)J recombination, making them highly diverse. By reconstructing BCR sequences, clinical labs can track clonal expansion, understand immune diversity, and monitor how the immune system reacts to pathogens, vaccines, or diseases. This insight is crucial for understanding immunity, developing immunotherapies, and designing vaccines.

Benchmark study compares popular tools for BCR reconstruction

A recent study published by Andreani et al. compared the performance of several popular tools for BCR reconstruction with scRNA-seq data (1), namely:

• MiXCR(2)
• BASIC(3)
• BRACER(4)
• BALDR(5)
• VDJPuzzle(6)
• TRUST4(7)

The study was then replicated by students in the Department of Biological and Chemical Engineering at Aarhus University with the addition of QIAGEN CLC Genomics Workbench v.23.0.5 (CLC) with the Biomedical Genomics Analysis plugin. Specifically, the Immune Repertoire Analysis tool of CLC was used, which was developed for bulk RNA-seq data and also included in the CLC Single Cell Analysis Module. Each single cell was treated as a separate sample. See the complete workflow.

The following dataset types were analyzed:

• Real data: Datasets with BCR sequences from actual immune cells (plasmablasts) obtained from earlier studies

• Simulated data: Datasets mimicking real-world scenarios with mutations in the BCR genes (heavy and light chains)

Results

The results, detailed here, show that:

1. CLC achieved the highest average score and performed well across all real and simulated datasets, followed by BASIC and BALDR.
2. CLC and BRACER excelled at reconstructing receptors in simulated datasets with added mutations.
3. CLC was the easiest to set up and use. Its user-friendly point-and-click interface requires no extra software installation or coding.
4. CLC was resource-efficient, as it completed the analysis on a standard laptop. See the minimum requirements to run CLC.

Conclusion

When working on BCR reconstruction (or NGS data in general), you want a tool with everything you might need. CLC offers a comprehensive toolset for immune repertoire analysis of single-cell data, among other applications.

• Streamlining workflows for clinical labs - CLC Genomics Workbench simplifies the traditionally complex immune repertoire analysis. With integrated, user-friendly interfaces, clinical professionals can rapidly align sequencing data and identify key immune cell populations. Automation and optimized algorithms make it easier to handle vast datasets, enabling labs to focus on actionable results.

• Enhancing speed and accuracy - In clinical settings, speed is critical. CLC Genomics Workbench accelerates analysis times by automating key processes like clonotype identification, annotation, and visualization. Its built-in reference databases and advanced tools for quality control ensure the highest level of accuracy, reducing manual errors and enhancing reproducibility across lab workflows.

• Clinical insights with actionable results - Beyond raw data, CLC Genomics Workbench delivers meaningful, clinical-grade insights. Its immune repertoire analysis tools help identify immune system dynamics crucial for diagnosing diseases, monitoring therapies, or personalizing treatments. Labs can confidently generate clinically relevant reports, ensuring rapid and accurate delivery of patient-specific results.

Download a free trial of CLC Genomics Workbench

For clinical labs seeking a robust, intuitive platform to enhance immune repertoire analysis, CLC Genomics Workbench offers a clear advantage. With its focus on speed, accuracy, and ease of use, labs can optimize their workflows and deliver high-quality clinical insights more efficiently than ever before.

Learn more or request a trial of CLC Genomics Workbench, your all-in-one toolkit.

References:

1. Andreani T, et al. NAR Genom Bioinform.2022;4(3).
2. Bolotin DA, et al.  Methods.2015;12:380–381.
3. Canzar S, et al. 2017;33:425–427.
4. Lindeman I, et al.  Methods.2018;15:563–565.
5. Upadhyay AA, et al. Genome Med.2018;10:20.
6. Rizzetto S, et al. 2018;34:2846–2847.
7. Song L, et al.  Methods.2021;18:627–630.

Author acknowledgments: We thank Dr. Tommaso Andreani, Senior Principal Data Scientist at Sanofi, for continuous support and encouragement during this study.