IgTree©: Creating Immunoglobulin variable region gene lineage trees

Michal Barak, Neta S. Zuckerman, Hanna Edelman, Ron Unger, Ramit Mehr

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

Abstract

Lineage trees describe the microevolution of cells within an organism. They have been useful in the study of B cell affinity maturation, which is based on somatic hypermutation of immunoglobulin genes in germinal centers and selection of the resulting mutants. Our aim was to create and implement an algorithm that can generate lineage trees from immunoglobulin variable region gene sequences. The IgTree© program implements the algorithm we developed, and generates lineage trees. Original sequences found in experiments are assigned to either leaves or internal nodes of the tree. Each tree node represents a single mutation separating the sequences. The mutations that separate the sequences from each other can be point mutations, deletions or insertions. The program can deal with gaps and find potential reversion mutations. The program also enumerates mutation frequencies and sequence motifs around each mutation, on a per-tree basis. The algorithm has proven useful in several studies of immunoglobulin variable region gene mutations.

Original languageEnglish
Pages (from-to)67-74
Number of pages8
JournalJournal of Immunological Methods
Volume338
Issue number1-2
DOIs
StatePublished - 30 Sep 2008

Bibliographical note

Funding Information:
The work was done as part of Michal Barak's studies towards a PhD degree in Bar-Ilan University, and was supported in parts by the following grants (to R.M.): Israel Science Foundation grants 759/01-1 and 546; an Israel Cancer Research Fund project grant; a Systems Biology prize grant from Teva Pharmaceuticals; Human Frontiers Science Program — a Young Investigator Grant and a Research Grant; and a Swedish Foundation for Strategic Research grant funding the IRIS Strategic Research Center, Karolinska Institute, Stockholm, Sweden; The ministry of Science and Technology PhD scholarship for advancing women in science; The Yeshaya Horowitz Association through the Center for Complexity Science PhD scholarship; Bar Ilan University President's PhD scholarship; and a Dean's excellence PhD scholarship of The Mina and Everard Goodman Faculty of Life Sciences (to NSZ). Ron Unger is partially supported by the Israeli Ministry of Science grant number 3-2559.

Keywords

  • B lymphocyte
  • Germinal center
  • Immunoglobulin variable region gene
  • Lineage tree
  • Phylogenetic tree

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