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Next-generation Sequencing03:00

Next-generation Sequencing

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The first human genome sequencing project cost $2.7 billion and was declared complete in 2003, after 15 years of international cooperation and collaboration between several research teams and funding agencies. Today, with the advent of next-generation sequencing technologies, the cost and time of sequencing a human genome have dropped over 100 fold.
Next-Generation Sequencing Methods
Although all next-generation methods use different technologies, they all share a set of standard features....
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Clonify: unseeded antibody lineage assignment from next-generation sequencing data.

Bryan Briney1,2,3, Khoa Le1,2,3, Jiang Zhu1,2,3

  • 1Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.

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Summary

Understanding antibody clonal lineages is key to humoral immunity. Our new algorithm, Clonify, reveals that antibody repertoire composition is less influenced by pathogen encounter history than previously believed.

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Area of Science:

  • Immunology
  • Computational Biology
  • Genomics

Background:

  • Humoral immune response and antibody maturation are critical for immunity.
  • Previous analyses of antibody lineages were limited to isolated studies.
  • Accurate clonal lineage assignment from next-generation sequencing data was lacking.

Purpose of the Study:

  • To develop an accurate algorithm for unseeded clonal lineage assignment in large antibody sequence datasets.
  • To analyze the influence of antibody lineages on the overall repertoire composition.

Main Methods:

  • Development of Clonify, an algorithm for unseeded lineage assignment.
  • Application of Clonify to analyze IgG+ memory repertoires from healthy individuals.

Main Results:

  • Clonify enables lineage assignment on very large antibody sequence sets.
  • Analysis revealed a surprising lack of influence of large extended lineages on repertoire composition.
  • Antibody repertoire composition appears less dependent on pathogen encounter order and frequency.

Conclusions:

  • Clonify is a valuable tool for comprehensive antibody lineage analysis.
  • Antibody repertoire composition is shaped by factors other than just the history of pathogen encounters.
  • This finding challenges previous assumptions about humoral immune memory formation.