Feb 10, 2017

Hierarchical Clustering Can Identify B Cell Clones with High Confidence in Ig Repertoire Sequencing Data

The Journal of Immunology : Official Journal of the American Association of Immunologists
Namita GuptaSteven H Kleinstein

Abstract

Adaptive immunity is driven by the expansion, somatic hypermutation, and selection of B cell clones. Each clone is the progeny of a single B cell responding to Ag, with diversified Ig receptors. These receptors can now be profiled on a large scale by next-generation sequencing. Such data provide a window into the microevolutionary dynamics that drive successful immune responses and the dysregulation that occurs with aging or disease. Clonal relationships are not directly measured, but they must be computationally inferred from these sequencing data. Although several hierarchical clustering-based methods have been proposed, they vary in distance and linkage methods and have not yet been rigorously compared. In this study, we use a combination of human experimental and simulated data to characterize the performance of hierarchical clustering-based methods for partitioning sequences into clones. We find that single linkage clustering has high performance, with specificity, sensitivity, and positive predictive value all >99%, whereas other linkages result in a significant loss of sensitivity. Surprisingly, distance metrics that incorporate the biases of somatic hypermutation do not outperform simple Hamming distance. Although error...Continue Reading

  • References48
  • Citations13

References

  • References48
  • Citations13

Mentioned in this Paper

In Silico
Study
Immune Response
Nucleic Acid Sequencing
CD23 Antigen
Statistical Cluster
Immunoglobulins
B-Lymphocytes
Clone
Cell Growth

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