immuneSIM

immuneSIM simulates human and mouse B- and T-cell receptor repertoires to generate customizable, annotated synthetic full-length variable region sequences for benchmarking and validation of immune-repertoire analysis methods.

Key Features:

• Repertoire simulation: Simulates human and mouse B-cell (BCR) and T-cell (TCR) repertoires with options for single or paired chain types, producing native-like or aberrant full-length variable region sequences.
• Germline gene usage: Incorporates user-specified germline gene usage patterns to reflect realistic immune receptor diversity.
• Insertion and deletion modeling: Simulates insertions and deletions that occur during V(D)J recombination to produce authentic junctional diversity.
• Clonal abundance control: Generates clone count distributions to simulate varying levels of clonal expansion or contraction.
• Somatic hypermutation (SHM): Includes configurable somatic hypermutation to model SHM events in BCR sequences.
• Motif implantation: Supports implantation of specific sequence motifs into simulated repertoires.
• In silico V(D)J recombination: Implements an in silico V(D)J recombination process to generate receptor diversity consistent with biological recombination events.
• Sequence annotation: Annotates each simulated sequence with the complete set of contributing simulation events.
• Benchmarking support: Provides datasets suitable for benchmarking germline gene annotation, diversity and overlap estimation, sequence similarity assessment, network architecture evaluation, clustering analysis, and machine learning methods for motif detection.

Scientific Applications:

• Benchmarking and validation: Generates ground-truth repertoires for benchmarking and validating computational tools for germline annotation, diversity estimation, clustering, and motif detection.
• Method development: Provides controlled datasets to develop and test new computational methods for immune repertoire analysis, including machine learning approaches.
• Diagnostics and therapeutics research: Enables evaluation of analytical approaches used in studies of B- and T-cell repertoires relevant to diagnostics and therapeutic development.

Methodology:

Implements in silico V(D)J recombination in an R package to generate annotated full-length variable region BCR and TCR sequences for human and mouse with user-specified germline gene usage, insertions/deletions, clone count distributions, somatic hypermutation, and motif implantation, and records contributing simulation events for each sequence.