CoMBCR: Co-Learning Multi-Modalities of BCRs and gene expressions

<h4>Motivation</h4>B-cell receptors (BCRs) and gene expression profiles are two distinct yet complementary modalities of B cells. However, most analyses treat them independently. Here, we present CoMBCR, a B-cell embedding tool that co-learns BCRs and gene expressions, representing data within a unified latent space for downstream analysis.<h4>Results</h4>We applied CoMBCR to 126,791 B cells from diverse datasets with matched BCRs and gene expressions. First, CoMBCR outperforms the methods solely encoding BCRs in capturing B-cell biological features, achieving at least 0.1 improvement in Matthews Correlation Coefficient on a SARS-CoV-2 binding prediction task. Second, CoMBCR reveals active immune responses and CDR3 motif preferences through modality gap analysis in SARS-CoV-2-specific memory B cells. Moreover, when supported by spatial transcriptomics data, CoMBCR accurately traces the developmental trajectories of malignant B cells and uncovers transcriptional patterns associated with their survival within lymphoma patients.<h4>Availability and implementation</h4>The CoMBCR software is publicly available under the MIT License at https://github.com/deepomicslab/CoMBCR.git.<h4>Contact</h4>[email protected].