dowser

dowser performs phylogenetic analyses of B cell receptor (BCR) repertoires from Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) to characterize B cell evolutionary processes including mutation, selection, migration, differentiation, and isotype switching.

Key Features:

• Phylogenetic tree construction and visualization: Builds and visualizes phylogenetic trees from BCR sequence data to represent clonal relationships and lineage structure.
• Parsimony-based summary statistics: Computes three parsimony-based statistics that quantify migration, differentiation, and isotype switching along phylogenetic trees of BCR sequences.
• Migration summary statistic: Quantifies movement of B cells between tissues by summarizing discrete trait changes on phylogenies using parsimony-based measures.
• Differentiation summary statistic: Characterizes transitions between cellular subsets by assessing parsimony-inferred state changes on B cell lineage trees.
• Isotype switching summary statistic: Evaluates changes in antibody isotype along B cell phylogenies using parsimony-based metrics.
• Statistical analysis for discrete traits: Implements statistical tests to infer significance of observed patterns in discrete traits such as tissue origin, cellular subset, and isotype.

Scientific Applications:

• High-throughput BCR sequence analysis: Infers patterns of cellular differentiation and isotype switching from AIRR-seq datasets using phylogenetic and parsimony-based methods.
• HIV infection studies: Applied to investigate cellular differentiation patterns in B cells from HIV-infected individuals.
• Food allergy research: Applied to analyze isotype switching patterns in individuals with food allergies.

Methodology:

Implements phylogenetic tree construction from BCR sequences, parsimony-based summary statistics for migration, differentiation, and isotype switching, statistical tests for discrete traits, and validation of the parsimony-based statistics using simulations within the Immcantation framework.