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Computational Evaluation of B-Cell Clone Sizes in Bulk Populations
Aaron M Rosenfeld1, Wenzhao Meng2, Dora Y Chen2
1School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA, United States.
Frontiers in Immunology
|July 17, 2018
Summary
This study introduces computational methods to estimate B cell clone size using next-generation sequencing (NGS) immune repertoire profiling. These methods help analyze B cell diversity and distribution in adaptive immunity and disease.
Area of Science:
- Immunology
- Computational Biology
- Genomics
Background:
- B cell clones are crucial in adaptive immunity and can become dysregulated in lymphoproliferative disorders.
- Next-generation sequencing (NGS) of antibody gene rearrangements is a key method for tracking B cell clones.
- Accurate estimation of B cell clone size is essential for understanding immune responses and disease.
Purpose of the Study:
- To present computational approaches for estimating B cell clone size from NGS immune repertoire profiling data.
- To define and apply different measures of B cell clone size (copy numbers, instances, unique sequences).
- To demonstrate the utility of these measures for analyzing B cell clone diversity and distribution.
Main Methods:
- Development and application of computational methods for analyzing antibody heavy chain gene rearrangements from NGS data.
- Definition of three distinct metrics for B cell clone size: copy numbers, instances, and unique sequences.
- Analysis of two datasets from human spleen samples, including biological replicates and multiple organ donors.
Main Results:
- Demonstrated how copy numbers, instances, and unique sequences can rank B cell clones and assess diversity.
- Provided a step-by-step procedure for analyzing B cell clone size in immune repertoire profiling data.
- Illustrated the application of these methods using real-world datasets, highlighting practical considerations.
Conclusions:
- The presented computational approaches offer pragmatic tools for studying the clonal landscape in bulk B cell immune repertoire profiling.
- Different clone size measures provide valuable insights into B cell dynamics during immune responses and disease.
- The study offers practical advice and addresses potential pitfalls in B cell repertoire analysis.
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